A patient with granulomatous amoebic encephalitis caused by Balamuthia mandrillaris survived with two excisions and medication

Background Granulomatous amoebic encephalitis (GAE) is a rare central nervous system infection caused by the Balamuthia mandrillaris or Acanthamoeba species. Diagnosis is challenging because of the non-specific clinical presentation, cerebrospinal fluid analysis, and radiological features. There is no effective treatment for GAE to date. Case presentation A 54-year-old male was admitted to hospital after experiencing acute onset of numbness and weakness on his left limb. Due to the initial consideration of intracranial tumor, surgical removal of the right parietal lesion was performed. However, the patient had a headache accompanied by diplopia, difficulty walking and a new lesion was found in the left occipital-parietal lobe two weeks after the first operation. High-throughput next-generation sequencing (NGS) detected the presence of high copy reads of the B. mandrillaris genome sequence in the patient’s blood, cerebral spinal fluid (CSF), and brain tissue. Pathological investigation of the brain tissue showed granulomatous changes and amoebic trophozoite scattered around blood vessels under high magnification. The patient was re-operated due to developing progressive confusion caused by subfalcine herniation of the left cerebral hemisphere. The lesions of the right parietal lobe were obviously decreasing in size after the first surgery, and the lesions of the left occipital lobe and the sunfalcine herniation didn’t ameliorate two months after the second surgery. The patient was transferred to local hospital for continuous treatment with sulfamethoxazole and azithromycin. After five months of the second surgery, the patient showed good recovery with mild headache. Conclusions This is the first report of a patient with B. mandrillaris encephalitis initially confirmed by NGS and have experienced two excisions, responding favorably to the combination of surgeries and medications. Early surgical resection of intracranial lesions combined with drug treatment may offer the chance of a cure.

How causal is a reciprocal effect? Contrasting traditional and new methods to investigate the reciprocal effects model of self-concept and achievement

The relationship between students’ subject-specific academic self-concept and their academic achievement is one of the most widely researched topics in educational psychology. A large body of this research has considered cross-lagged panel models (CLPMs), oftentimes synonymously referred to as reciprocal effects models (REMs), as a gold standard to investigate the causal relations between the two variables and has reported evidence for a reciprocal relationship between self-concept and achievement. However, more recent methodological research questioned the plausibility of assumptions that need to be satisfied in order to interpret results from traditional CLPMs causally. In this substantive-methodological synergy, we aimed at contrasting traditional and more recently developed methods to investigate reciprocal effects of students’ academic self-concept and achievement. Specifically, we compared results from CLPMs, from full forward CLPMs (FF-CLPMs), and from random intercept CLPMs (RI-CLPMs) with two weighting approaches developed to study causal effects of continuous treatment variables. To estimate these different models, we used rich longitudinal data of N = 3,757 students from lower secondary schools in Germany. Results from CLPMs, FF-CLPMs, and weighting methods support the reciprocal effects model, particularly when considering math self-concept and grades. In contrast, results from the RI-CLPMs were less consistent. Implications from our study for the interpretation of effects from the different models and methods as well as for school motivation theory are discussed.

The Effect of Combination Use of Hemodialysis and Hemoperfusion on Microinflammation in Elderly Patients with Maintenance Hemodialysis

<b><i>Background:</i></b> Patients with maintenance hemodialysis (MHD) generally have a microinflammatory state. The aim of this study was to investigate the effects of hemodialysis (HD) combined with hemoperfusion (HP) on microinflammatory state in elderly patients with MHD. <b><i>Methods:</i></b> One hundred and fifty elderly patients with MHD were randomly divided into the control group and the observation group. The control group received simple HD treatment, and the observation group received combined HD + HP treatment on the basis of the control group. After 6 months of continuous treatment, the patients were evaluated to compare the quality of life, inflammation, adverse reactions, and nutritional indicators in the 2 groups before and after treatment. <b><i>Results:</i></b> There was no significant difference in the quality of life between the 2 groups before treatment. After treatment, the scores of psychological aspects, physiological aspects, social aspects, environmental aspects, and independent ability in the observation group were higher than those in the control group, with statistical significance (<i>p</i> &#x3c; 0.05). There was no statistical significance in the level of inflammation between 2 groups before treatment. After treatment, the levels of hs-CRP, Hcy, IL-6, and TNF-α in the observation group were significantly lower than those in the control group, with statistical significance (<i>p</i> &#x3c; 0.05). The incidence of dry mouth, skin reaction, neuritis, and subcutaneous tissue fibrosis in the observation group was lower than that in the control group, with statistical significance (<i>p</i> &#x3c; 0.05). There was no statistical significance in nutritional level indexes between 2 groups before treatment (<i>p</i>₁ &#x3e; 0.05). After treatment, the levels of hemoglobin, total protein, albumin, and transferrin in the observation group were significantly higher than those in the control group, with statistical significance (<i>p</i> &#x3c; 0.05). <b><i>Conclusion:</i></b> The clinical effect of HD combined with HP in elderly MHD patients is significant, which can effectively reduce the incidence of adverse reactions and inflammation in the patients and improve the quality of life and nutritional indicators of the patients.

Frequent Quantitation of Circulating Tumor Cells Predictive of Real-Time Therapy Response

Precision medicine is playing an increasingly important role in cancer management and treatment. Specifically in the field of oncology, circulating tumor cells (CTCs) hold significant promise in enabling non-invasive prognostication and near real-time monitoring to individualize treatments. In this study, we present strong associations between CTC subtype counts with treatment response and tumor staging in lung, nasopharyngeal and breast cancers. Longitudinal analysis of CTC count changes over short-time windows further reveals the ability to predict treatment response close to real-time. Our findings demonstrate the suitability of CTCs as a definitive blood-based metric for continuous treatment monitoring. Robust processing of high-throughput image data, explainable classification of CTC subtypes and accurate quantification were achieved using an in-house image analysis system CTC-Quant, which showed excellent agreement with expert opinion upon extensive validation.

Differential Effects of Acute and Chronic Antagonist And An Irreversible Antagonist Treatment On Cocaine Self-Administration Behavior in Rats

According to pharmacological theory, the magnitude of an agonist-induced response is related to the number of receptors occupied. If there is a receptor reserve, when the number of receptors is altered the fractional occupancy required to maintain this set number of receptors will change. Therefore, any change in dopamine receptor number will result in a change in the concentration of cocaine required to induce the satiety response. Rats that self-administered cocaine were treated with the irreversible monoamine receptor antagonist, EEDQ, or were infused continuously for 14 days with the D1-like antagonist, SCH23390, treatments known to decrease or increase, respectively, the number of dopamine receptors with a concomitant decrease or increase in response to dopaminergic agonists. The rate of maintained cocaine self-administration increased or decreased in rats treated with EEDQ or withdrawn from chronic SCH23390 infusion, respectively. After EEDQ treatment, the effect ratio of a single dose of SCH23390 or eticlopride were unchanged, indicating that the same dopamine receptor populations mediated the accelerated cocaine self-administration. The satiety threshold likely corresponds to a specific number of activated dopamine receptors. Changing the receptor reserve is a key determinant of the rate of cocaine self-administration because the resulting increased or decreased concentration of cocaine results in an accelerated or decelerated rate of cocaine elimination as dictated by first-order kinetics. Changes in dopamine receptor number that may occur after continuous treatment with antagonists may account for the apparent lack of efficacy of these antagonists in clinical trials for cocaine use disorder.

Differential Discontinuation Profiles between Pirfenidone and Nintedanib in Patients with Idiopathic Pulmonary Fibrosis

Antifibrotic agents have been widely used in patients with idiopathic pulmonary fibrosis (IPF). Long-term continuation of antifibrotic therapy is required for IPF treatment to prevent disease progression. However, antifibrotic treatment has considerable adverse events, and the continuation of treatment is uncertain in many cases. Therefore, we examined and compared the continuity of treatment between pirfenidone and nintedanib in patients with IPF. We retrospectively enrolled 261 consecutive IPF patients who received antifibrotic treatment from six core facilities in Gunma Prefecture from 2009 to 2018. Among them, 77 patients were excluded if the antifibrotic agent was switched or if the observation period was less than a year. In this study, 134 patients treated with pirfenidone and 50 treated with nintedanib were analyzed. There was no significant difference in patient background, discontinuation rate of antifibrotic treatment over time, and survival rate between the two groups. However, the discontinuation rate due to adverse events within one year of antifibrotic treatment was significantly higher in the nintedanib group than in the pirfenidone group (76% vs. 37%, p < 0.001). Furthermore, the discontinuation rate due to adverse events in nintedanib was higher than that of pirfenidone treatment throughout the observation period (70.6% vs. 31.2%, p = 0.016). The pirfenidone group tended to be discontinued due to acute exacerbation or transfer to another facility. The results of this study suggest that better management of adverse events with nintedanib leads to more continuous treatment that prevents disease progression and acute exacerbations, thus improving prognosis in patients with IPF.

Response to Fungicides of Colletotrichum spp. Isolated from Red Peppers in Sunchang, Korea

In August 2020, 377 anthracnose strains were isolated from anthracnose-infected peppers collected from 25 farms in Sunchang-gun, Jeollabuk-do. Inhibition rate of mycelial growth of 11 pepper anthracnose fungicides registered in Korea was investigated for 62 strains selected by region and the degree of susceptibility to each fungicide was investigated. As a result of the fungicide susceptibility test of anthracnose to the fungicide, no resistant strains were observed in fluazinam, prochloraz manganese, and benomyl, but resistant strains appeared in at least three areas for other fungicides, and all strains in all regions were resistant to dithianon. Through this, it was confirmed that the fungicide resistance was expressed in the strain group due to the continuous treatment of the fungicide in some areas. By region, resistant strains to seven pesticides appeared in Sunchang-eup and Paldeok-myeon, and resistant strains to six pesticides appeared in Geumgwa-myeon, Bokheung-myeon, Ssangchi-myeon, Yudeung-myeon, and Pungsan-myeon. There was no significant correlation between fungicide registration time and emergence of resistant strains.

Long-Term Survival of a Patient with Hepatocellular Carcinoma under Treatment with Viscum album – Case Report

Hepatocellular carcinoma (HCC) is the most common liver neoplasm in dogs and can be treated by the Viscum album therapy in a curative or palliative way. The objective is to report a hepatocellular carcinoma case in a dog treated by homeopathic therapy, extending to Palliative Care, with a 24-month survival. A 12-year-old Schnauzer male with a history of a liver nodule was treated by intravenous and subcutaneous applications of V. album in different dynamization and combinations, chromotherapy, and oral homeopathic medicines. The tumor growth was controlled, and the health condition of the patient was stable while the medication was given as prescribed. However, as application frequency was reduced, tumor growth increased, and health deterioration was verified. Nevertheless and contrary to expectations, the patient had a 24-month survival. Therefore, these findings point to the potential of V. album on enhancing the quality of life, controlling tumor growth, and prolonging survival on patients with HCC. Patients under continuous treatment would benefit better of these properties.

Entropy Balancing for Continuous Treatments

Interest in evaluating the effects of continuous treatments has been on the rise recently. To facilitate the estimation of causal effects in this setting, the present paper introduces entropy balancing for continuous treatments (EBCT) – an intuitive and user-friendly automated covariate balancing scheme – by extending the original entropy balancing methodology of Hainmueller, J. 2012. “Entropy Balancing for Causal Effects: A Multivariate Reweighting Method to Produce Balanced Samples in Observational Studies.” Political Analysis 20 (1): 25–46. In order to estimate balancing weights, the proposed approach solves a globally convex constrained optimization problem, allowing for computationally efficient software implementation. EBCT weights reliably eradicate Pearson correlations between covariates (and their transformations) and the continuous treatment variable. As uncorrelatedness may not be sufficient to guarantee consistent estimates of dose–response functions, EBCT also allows to render higher moments of the treatment variable uncorrelated with covariates to mitigate this issue. Empirical Monte-Carlo simulations suggest that treatment effect estimates using EBCT display favorable properties in terms of bias and root mean squared error, especially when balance on higher moments of the treatment variable is sought. These properties make EBCT an attractive method for the evaluation of continuous treatments. Software implementation is available for Stata and R.