Sykeswestergaard4234
Hereditary spherocytosis (HS) is the most common inherited chronic haemolytic anaemia in Northern Europe. During the last decade, additional erythrocyte and reticulocyte parameters have been developed on last-generation haematology analysers, leading to many publications about their effectiveness as a HS screening tool. For the first time on an independent cohort, we evaluated and compared the effectiveness of six published algorithms for the screening of HS using the UniCel DxH800 (Beckman-Coulter) and the XN-9000 (Sysmex) and determined which algorithm could be the most suitable in our daily clinical practice. A total of 95 EDTA samples were analysed prospectively on both haematology analysers. These included 11 confirmed HS patients and 84 non-HS patients. The specific reticulocyte parameters used on the DxH800 were mean reticulocyte volume, immature reticulocyte fraction and mean sphered cell volume, and on the XN-9000 were hypohaemoglobinised erythrocytes, microcytic erythrocytes and immature reticulocyte fraction. The three algorithms using parameters specific to Beckman-Coulter analysers provided a sensitivity of 100% with various specificities, ranging from 7.1 to 73.8%. The three algorithms published based on the parameters specific to Sysmex showed much lower performances, i.e. out of the 11 patients with HS, between one to five patients were screened as negative for HS. SAHA However, 100% sensitivity and specificity were reached using the EMA binding test concomitantly with those three algorithms. The algorithms using reticulocyte and erythrocyte parameters offered by the recent analysers are promising options as a HS first-tier screening tool. Nevertheless, they must be evaluated by each laboratory on their own analyser before implementation.
To determine how particle density affects dose distribution and outcomes after lobar radioembolization.
Matched pairs of patients, treated with glass versus resin microspheres, were selected by propensity score matching (114 patients), in this single-institution retrospective study. For each patient, tumor and liver particle density (particles/cm
) and dose (Gy) were determined. Tumor-to-normal ratio was measured on both
Tc-MAA SPECT/CT and post-
Y bremsstrahlung SPECT/CT. Microdosimetry simulations were used to calculate first percentile dose, which is the dose in the cold spots between microspheres. Local progression-free survival (LPFS) and overall survival were analyzed.
As more particles were delivered, doses on
Y SPECT/CT became more uniform throughout the treatment volume tumor and liver doses became more similar (p = 0.04), and microscopic cold spots between particles disappeared. For hypervascular tumors (tumor-to-normal ratio ≥ 2.6 on MAA scan), delivering fewer particles (< 6000 particles/cm
treatment volume) was associated with better LPFS (p = 0.03). For less vascular tumors (tumor-to-normal ratio < 2.6), delivering more particles (≥ 6000 particles/cm
) was associated with better LPFS (p = 0.02). In matched pairs of patients, using the optimal particle density resulted in improved overall survival (11.5 vs. 6.8months, p = 0.047), compared to using suboptimal particle density. Microdosimetry resulted in better predictions of LPFS (p = 0.03), and overall survival (p = 0.02), compared to conventional dosimetry.
The number of particles delivered can be chosen to maximize the tumor dose and minimize the liver dose, based on tumor vascularity. Optimizing the particle density resulted in improved LPFS and overall survival.
The number of particles delivered can be chosen to maximize the tumor dose and minimize the liver dose, based on tumor vascularity. Optimizing the particle density resulted in improved LPFS and overall survival.
Although the occurrence of stressful events is very common during life, their impact may be different depending on the experience severity and duration. Specifically, acute challenges may trigger adaptive responses and even improve the individual's performance. However, such a physiological positive coping can only take place if the underlying molecular mechanisms are properly functioning. Indeed, if these systems are compromised by genetic factors or previous adverse conditions, the response set in motion by an acute challenge may be maladaptive and even cause the insurgence or the relapse of stress-related psychiatric disorders.
On these bases, we evaluated in the rat brain the role of the antioxidant component of the redox machinery on the acute stress responsiveness and its modulation by potential detrimental or beneficial events.
The expression of several antioxidant enzymes was assessed in different brain areas of adult male rats exposed to acute stress 3weeks after a chronic immobilization paradigm with or without a concomitant treatment with the antipsychotic lurasidone.
The acute challenge was able to trigger a marked antioxidant response that, despite the washout period, was impaired by the previous adverse experience and restored by lurasidone in an anatomical-specific manner.
We found that a working antioxidant machinery takes part in acute stress response and may be differentially affected by other experiences. Given the essential role of stress responsiveness in almost every life process, the identification of the underlying mechanisms and their potential pharmacological modulation add further translational value to our data.
We found that a working antioxidant machinery takes part in acute stress response and may be differentially affected by other experiences. Given the essential role of stress responsiveness in almost every life process, the identification of the underlying mechanisms and their potential pharmacological modulation add further translational value to our data.Emerging evidence has implicated the endogenous opioid system in mediating ketamine's antidepressant activity in subjects with major depressive disorder. To date, mu opioid receptors have been suggested as the primary opioid receptor of interest. However, this hypothesis relies primarily on observations that the opioid antagonist naltrexone blocked the effects of ketamine in humans and rodents. This report confirms previous findings that pretreatment with naltrexone (1 mg/kg) just prior to ketamine (10 mg/kg) administration effectively blocks the behavioral effect of ketamine in the mouse forced swim test 24 h post-treatment. Furthermore, pharmacological blockade of kappa opioid receptors prior to ketamine administration with the selective, short-acting antagonist LY2444296 successfully blocked ketamine's effects in the forced swim test. Likewise, the ability of the ketamine metabolite (2R,6R)-hydroxynorketamine to reduce immobility scores in the forced swim test was also blocked following pretreatment with either naltrexone or LY2444296. These data support a potential role of kappa opioid receptors in mediating the behavioral activity of ketamine and its non-dissociate metabolite (2R,6R)-hydroxynorketamine.
Human papillomavirus (HPV) status assessment is crucial for decision making in oropharyngeal cancer patients. In last years, several articles have been published investigating the possible role of radiomics in distinguishing HPV-positive from HPV-negative neoplasms. Aim of this review was to perform a systematic quality assessment of radiomic studies published on this topic.
Radiomics studies on HPV status prediction in oropharyngeal cancer patients were selected. The Radiomic Quality Score (RQS) was assessed by three readers to evaluate their methodological quality. In addition, possible correlations between RQS% and journal type, year of publication, impact factor, and journal rank were investigated.
After the literature search, 19 articles were selected whose RQS median was 33% (range 0-42%). Overall, 16/19 studies included a well-documented imaging protocol, 13/19 demonstrated phenotypic differences, and all were compared with the current gold standard. No study included a public protocol, phantom study, or imaging at multiple time points. More than half (13/19) included feature selection and only 2 were comprehensive of non-radiomic features. Mean RQS was significantly higher in clinical journals.
Radiomics has been proposed for oropharyngeal cancer HPV status assessment, with promising results. However, these are supported by low methodological quality investigations. Further studies with higher methodological quality, appropriate standardization, and greater attention to validation are necessary prior to clinical adoption.
Radiomics has been proposed for oropharyngeal cancer HPV status assessment, with promising results. However, these are supported by low methodological quality investigations. Further studies with higher methodological quality, appropriate standardization, and greater attention to validation are necessary prior to clinical adoption.We describe how the fusion process between magnetic resonance angiography (MRA) and cisternography (MRC) promptly reveals vessel anatomy ahead of the clot, in patients affected by acute anterior circulation large vessel occlusion. This technique showed in 100% of subjects (n = 22) a clear tracing of vessel anatomy before and beyond the clot. The duration of the whole process is short and could be considered safe since no outcome differences have been found when compared with a control group (n = 23). This technique could play a relevant role in guiding endovascular therapy, especially in unexpected unfavorable anatomical arteries configurations.KCNQ channels participate in the physiology of several cell types. In neurons of the central nervous system, the primary subunits are KCNQ2, 3, and 5. Activation of these channels silence the neurons, limiting action potential duration and preventing high-frequency action potential burst. Loss-of-function mutations of the KCNQ channels are associated with a wide spectrum of phenotypes characterized by hyperexcitability. Hence, pharmacological activation of these channels is an attractive strategy to treat epilepsy and other hyperexcitability conditions as are the evolution of stroke and traumatic brain injury. In this work we show that triclosan, a bactericide widely used in personal care products, activates the KCNQ3 channels but not the KCNQ2. Triclosan induces a voltage shift in the activation, increases the conductance, and slows the closing of the channel. The response is independent of PIP2. Molecular docking simulations together with site-directed mutagenesis suggest that the putative binding site is in the voltage sensor domain. Our results indicate that triclosan is a new activator for KCNQ channels.
Chemotherapy is the cornerstone of adjuvant therapy in ovarian cancer. Its impact on the quality of life (QoL) has been addressed in several studies; however, several misperceptions concerning this affect patient counseling and physicians' ability to overcome patient fears. In the present systematic review, we sought to accumulate current evidence in the field in order to help establish robust information that will help physicians answer patients' questions.
The present systematic review is based on the PRISMA guidelines. Studies that evaluated patient QoL pre-, during, and post-chemotherapy with the use of the QLQC-30 were selected for inclusion. Their methodological quality was assessed with the before-after studies tool that is proposed by the National Institute of Health (NIH).
Ten studies that involved 5181 patients were included in the present systematic review. The risk of bias and methodological quality of included studies was of good and fair overall quality. Retrieved data suggest there is substantial evidence that points toward improved global QoL among ovarian cancer patients treated with taxanes-platinum combination therapy.
