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Nafamostat mesilate attenuates short-term focal ischemia/reperfusion-induced injury to the brain through self-consciousness of endoplasmic reticulum tension.
In this work, we evaluated whether the species Myriophyllum aquaticum (Vell.) Verdc. can be a promising material for devising reliable eco-toxicological tests for Cd-contaminated waters. Plants of M. aquaticum were exposed to Cd, using different concentrations (1 mg L-1, 2.5 mg L-1, 5 mg L-1, and 10 mg L-1; experiment 1) and exposure times (2.5 mg L-1 for 3 days, 7 days, 14 days, and 21 days; experiment 2). Plant growth and Cd accumulation were monitored during the treatment period, and Cd genotoxicity was assessed by analyzing Cd-induced changes in the AFLP fingerprinting profiles using famEcoRI(TAC)/MseI(ATG) and hexEcoRI(ACG)/MseI(ATG) pairs of primers. Root and shoot growth was reduced already at the lowest Cd concentration used (about 20% reduction for roots and 60% for shoots at 1 mg L-1; experiment 1) and after 7 days (about 50% reduction for roots and 70% for shoots; experiment 2). The primer combinations produced 154 and 191 polymorphic loci for experiments 1 and 2, respectively. Mean genetic diversity (He) reduction among the treatment groups was observed starting from 2.5 mg L-1 (He 0.211 treated vs 0.236 control; experiment 1) and after 3 days (He 0.169 treated vs 0.261 control; experiment 2), indicating that results obtained from AFLP profiles did not match with plant growth measurements. Therefore, our results showed that M. aquaticum proved to be a suitable model system for the investigation of Cd genotoxicity through AFLP fingerprinting profile, whereas the more classic eco-toxicological tests based only on biometric parameters could not correctly estimate the risk associated with undetected Cd genotoxicity.
Fatigue is one of the most common and debilitating symptoms of multiple sclerosis (MS) but is challenging to assess and has not been comprehensively characterized in patients with progressive MS. This study aimed to (1) obtain qualitative evidence from patients with progressive MS to characterize MS-related fatigue concepts and their impacts on health-related quality of life (HRQoL), and (2) evaluate the conceptual frameworks of existing MS-specific fatigue patient-reported outcome (PRO) instruments using study data to determine the most suitable PRO instrument in this population.

Qualitative interviews were conducted with 30 US participants with confirmed progressive MS and fatigue in the last 6months to assess their MS-related fatigue. Data were compared with concepts in existing PRO instruments to evaluate their relevance in progressive MS.

Physical and mental concepts of fatigue were identified and characterized distinctly from patients with progressive MS. Most patients characterized fatigue as occurring daily and lasting several hours, with negative impacts on HRQoL. Concept mapping to existing MS-specific fatigue PRO instruments supported the Fatigue Severity Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) as the most suitable existing option for assessing fatigue in patients with progressive MS, as it separates physical and mental aspects of fatigue and includes every highly endorsed concept reported by the interviewed patients.

This qualitative study identified meaningful physical and mental fatigue concepts in patients with progressive MS and preliminarily supports the use of the FSIQ-RMS for this population. More research is needed to fully validate this instrument for progressive MS.
This qualitative study identified meaningful physical and mental fatigue concepts in patients with progressive MS and preliminarily supports the use of the FSIQ-RMS for this population. More research is needed to fully validate this instrument for progressive MS.Patients with lung cancer at the same stage may have markedly different overall outcome and a lack of specific biomarker to predict lung cancer outcome. Heat-shock protein 90 β (HSP90β) is overexpressed in various tumor cells. In this study, the ELISA results of HSP90β combined with CEA, CA125, and CYFRA21-1 were used to construct a recursive partitioning decision tree model to establish a four-protein diagnostic model and predict the survival of patients with lung cancer. Survival analysis showed that the recursive partitioning decision tree could distinguish the prognosis between high- and low-risk groups. Results suggested that the joint detection of HSP90β, CEA, CA125, and CYFRA21-1 in the peripheral blood of patients with lung cancer is plausible for early diagnosis and prognosis prediction of lung cancer.Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high disability and mortality. Clinical studies have shown that the Traditional Chinese Medicine Bufei Granule (BFG) has conspicuous effects on relieving cough and improving lung function in patients with COPD and has a reliable effect on the treatment of COPD, whereas the therapeutic mechanism is vague. In the present study, the latent bronchodilators and mechanism of BFG in the treatment of COPD were discussed through the method of network pharmacology. Then, the molecular docking and molecular dynamics simulation were performed to calculate the binding efficacy of corresponding compounds in BFG to muscarinic receptor. Finally, the effects of BFG on bronchial smooth muscle were validated by in vitro experiments. The network pharmacology results manifested the anti-COPD effect of BFG was mainly realized via restraining airway smooth muscle contraction, activating cAMP pathways and relieving oxidative stress. The results of molecular docking and molecular dynamics simulation showed alpinetin could bind to cholinergic receptor muscarinic 3. The in vitro experiment verified both BFG and alpinetin could inhibit the levels of CHRM3 and acetylcholine and could be potential bronchodilators for treating COPD. This study provides an integrating network pharmacology method for understanding the therapeutic mechanisms of traditional Chinese medicine, as well as a new strategy for developing natural medicines for treating COPD.Cognitive-attentional syndrome (CAS) is in the self-regulatory executive function model a set of cognitive and behavioural strategies aimed at regulating cognition and emotion originating from maladaptive metacognitive beliefs. Investigating the brain structure of people with high levels of CAS enables a better understanding of the syndrome and bridging between the metacognitive model of psychopathology and previous results on structural abnormalities in various psychological disorders. Participants with high (n=40) and low levels of CAS (n=44) underwent structural Magnetic Resonance Imaging session. Voxel-Based Morphometry analytical approach was used to compute grey matter volume (GMV) differences between the groups. The group with a high level of CAS had lower GMV in the dorsal part of the anterior cingulate cortex. Our results are in line with the self-regulatory executive function model of psychopathology, showing a link between CAS and lowered GMV in the brain region associated with the regulation of cognition and emotion. They are also in agreement with meta-analytical results on structural correlates of various psychological disorders.Life expectancy in adults with congenital heart disease (ACHD) has increased. As these patients grow older, they experience aging-related diseases more than their healthy peers. To better characterize this field, we launched the multi-disciplinary BACH (Brain Aging in Congenital Heart disease) San Donato study, that aimed at investigating signs of brain injury in ACHD. Twenty-three adults with repaired tetralogy of Fallot and 23 age- and sex-matched healthy controls were prospectively recruited and underwent brain magnetic resonance imaging. White matter hyperintensities (WMHs) were segmented using a machine-learning approach and automatically split into periventricular and deep. Cerebral microbleeds were manually counted. A subset of 14 patients were also assessed with an extensive neuropsychological battery. Age was 41.78 ± 10.33 years (mean ± standard deviation) for patients and 41.48 ± 10.28 years for controls (p = 0.921). Albeit not significantly, total brain (p = 0.282) and brain tissue volumes (p = 0.539 for cerebrospinal fluid, p = 0.661 for grey matter, p = 0.793 for white matter) were lower in ACHD, while total volume (p = 0.283) and sub-classes of WMHs (p = 0.386 for periventricular WMHs and p = 0.138 for deep WMHs) were higher in ACHD than in controls. Deep WMHs were associated with poorer performance at the frontal assessment battery (r = -0.650, p = 0.012). Also, patients had a much larger number of microbleeds than controls (median and interquartile range 5 [3-11] and 0 [0-0] respectively; p  less then  0.001). In this study, adults with tetralogy of Fallot showed specific signs of brain injury, with some clinical implications. Eventually, accurate characterization of brain health using neuroimaging and neuropsychological data would aid in the identification of ACHD patients at risk of cognitive deterioration.
Parenchyma-sparing (PS) liver resection is recommended for liver tumors. The value of PS-approaches as compared to more extended resections is unknown. We sought to examine value-based differences (quality/cost) of central hepatectomy (CH) versus more extended resections.

A retrospective cohort study including consecutive patients having CH or right/extended hepatectomies (R/EH) at a high-volume cancer center was performed (2015-2019). The primary outcome was the value ratio, calculated as quality/cost. Quality was defined as the proportion of patients achieving a textbook outcome. Perioperative actual direct costs ($USD) for each patient were abstracted from institutional financial records spanning throughout the perioperative period. Value ratios were calculated and compared for each approach; sensitivity analysis was performed by modelling TO and cost thresholds.

Among 651 hepatobiliary operations (426 liver resections), 90 patients met inclusion criteria 19 CH and 71 R/EH. TO occurred in 68% and 69% of CH and R/EH, respectively (P = 0.96). Mean direct costs were $21,826 for CH and $28,599 for R/EH (P = 0.008). CH provided a greater value (value ratio CH = 0.33 vs. R/EH = 0.26; P = 0.004) with a shift favoring R/EH only when the TO threshold for CH was below 51% (CH = 0.23 vs. R/EH = 0.24) or that of R/EH was over 90% (CH = 0.31 vs. R/EH = 0.32).

These findings support a PS approach for central liver tumors (central hepatectomy) as it offers higher value than more extended resections. In the context of high-volume centers with outcomes within established national benchmarks, patients with central tumors should be considered for CH over more extended non-PS approaches.
These findings support a PS approach for central liver tumors (central hepatectomy) as it offers higher value than more extended resections. In the context of high-volume centers with outcomes within established national benchmarks, patients with central tumors should be considered for CH over more extended non-PS approaches.
Neonatal hypertension is increasingly recognized as improvements in neonatal intensive care have led to increased survival of premature infants. Among infants with bronchopulmonary dysplasia (BPD), the rates of hypertension are much higher than the general neonatal population. However, the etiology and pathophysiology of this increased risk of hypertension in neonates with lung disease remain unclear.

Among infants with bronchopulmonary dysplasia, the rates of hypertension are much higher than the general neonatal population. New studies suggest outcomes in neonates with BPD with hypertension are usually good, with resolution of hypertension in most infants with lung disease. Several potential mechanisms of hypertension in this patient population have been recently proposed. This review focuses on the recent epidemiologic data on prevalence of hypertension in neonates with bronchopulmonary dysplasia, reviews the typical clinical course, and discusses available strategies for management of infants with bronchopulmonary dysplasia that develop hypertension.
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