Freezing of gait subtypes have different cognitive correlates in Parkinson's disease

BackgroundFreezing of gait (FOG) is a major concern for Parkinson's disease (PD) patients because it is a leading cause of falls and is associated with poor quality of life. The pathophysiology is unknown but it is hypothesized that it relates to cognitive abnormalities; particularly executive and visuospatial dysfunction. However, prior results have been discrepant. Pharmacologic subtypes of FOG include those that are responsive and unresponsive to levodopa.ObjectiveTo determine whether executive and visuospatial dysfunction are associated specifically with the levodopa unresponsive subtype of FOG.Methods135 PD subjects completed a single assessment included FOG questionnaire, UPDRS motor scale, comprehensive cognitive battery and measure of hallucinations. Analyses compared unresponsive (n = 16), responsive (n = 20) and no FOG (n = 99) subtypes.ResultsThe unresponsive subtype had a significantly older age of onset of PD than the responsive group (p = .03) and had worse motor scores (p = .003) than the no FOG group. Longer disease duration was associated with the responsive group compared to the no FOG group (p = .002). The unresponsive FOG group had significantly poorer visuospatial ability (p = .001) and executive functioning (p = .02) than both the no and responsive FOG subgroups. These latter groups were not significantly different. The responsive FOG group was associated with the presence of hallucinations.ConclusionAside from pharmacological differences, unresponsive FOG is associated with executive and visuospatial dysfunction implicating frontostriatal pathways while responsive FOG is associated with hallucinations suggesting involvement of posterior cortical regions. Further study and treatment of FOG should include appropriate subtype classification.     

Dynamic chromatin loops bridge health and disease in the nuclear landscape

The genome is dynamically organized in the nuclear space in a manner that reflects and influences nuclear functions. Developmental processes that govern the formation and maintenance of epigenetic memories are also tightly linked to adaptive changes in the physical and functional landscape of the nuclear architecture. Biological and biophysical principles governing the three-dimensional folding of chromatin are therefore central to our understanding of epigenetic regulation during adaptive responses and in complex diseases, such as cancer. Accumulating evidence points to the direction that global alterations in nuclear architecture and chromatin folding conspire with unstable epigenetic states of the primary chromatin fiber to drive the phenotypic plasticity of cancer cells.     

Hepatic ischemia-reperfusion increases circulating bone marrow-derived progenitor cells and tumor growth in a mouse model of colorectal liver metastases

BackgroundHepatic pedicle clamping is often required to reduce blood loss and transfusion during liver resection. However, the question remains whether use of hepatic pedicle clamping promotes tumor growth. Endothelial progenitor cells (EPCs) are mobilized from bone marrow in response to tissue ischemia, which allows neovascularization of ischemic tissue. It has been suggested that EPCs are involved in tumor progression. We hypothesized that hepatic ischemia reperfusion (I/R)-induced mobilization of EPCs could enhance growth of microscopic tumor, therefore promoting liver metastasis in a mouse model of colorectal cancer.Materials and methodsWe used mouse models of hepatic I/R and hind limb ischemia. For comparison, we studied mice that underwent limb ischemia as positive controls of EPC mobilization. At day 0, we divided 40 mice into four groups: hepatic I/R, hind limb ischemia, combined hepatic I/R and hind limb ischemia, and control (sham midline incision laparotomy). At day 2, we induced liver metastasis in all mice by injecting CT-26 cells into the spleen. Time-dependent circulating EPCs were determined by flow cytometry. We evaluated liver metastasis and microvascular density on day 21.ResultsThe number of circulating progenitor cells increased rapidly in the ischemic groups compared with the control group. Hepatic I/R significantly increased tumor outgrowth compared with the control group. Increased tumor growth was associated with enhanced CD31-positive microvascular density in liver tissue.ConclusionsHepatic I/R leads to mobilization of bone marrow–derived EPCs and enhanced intra-hepatic angiogenesis, which is associated with increased tumor burden in an animal model of colorectal liver metastasis.     

Exploration of simulation-based medical education for undergraduate students

Over the past decades, extensive studies have underscored the growing importance of simulation-based medical education (SBME) for medical students. However, the underlying influence of SBME on undergraduate students is yet to be investigated. This work is a single-center cohort study involving 1178 undergraduate students who were divided into a control group and an SBME group. All participants gave their written informed consent. We compared the theoretical and practical achievements of these 2 groups and distributed a feedback questionnaire. Results show that SBME significantly improves the practical or theoretical achievements of students (P < .001). The humanistic care (improvement rate: 69.2%) and doctor–patient communication (improvement rate: 56.3%) performances of these studies were vastly improved. The students in the SBME group tend to allocate more time to communicating with others. SBME is an effective teaching method that can improve the reflective capacity and communication skills of undergraduate medical students, thereby resulting in their relatively improved performance.     

Evaluation of adalimumab biosimilar candidate (HS016) in Chinese patients with active ankylosing spondylitis based on a health survey: sub-analysis of a phase 3 study

Clinical Rheumatology - The equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to...     

Comparison of the efficacy and safety of the adalimumab biosimilar TQ-Z2301 and adalimumab for the treatment of Chinese patients with active ankylosing spondylitis: a multi-center,randomized, double-blind,phase III clinical trial

Clinical Rheumatology - To assess the clinical equivalence of TQ-Z2301, a biosimilar of adalimumab, to the reference adalimumab in the treatment of Chinese patients with active ankylosing...     

成人小脑髓母细胞瘤MR成像和NSE表达水平

目的:探讨成人小脑髓母细胞瘤的MRI表现及神经元特异性烯醇化酶(Neuron-Specific Enolase,NSE)特点。方法:对17例经手术病理证实的成人小脑髓母细胞瘤的MR表现进行分析。免疫组化法检测肿瘤组织中NSE表达。ELISA试剂盒检测血清NSE水平。结果 :髓母细胞瘤均位于小脑半球,其中右侧11例,左侧6例,部分累及小脑蚓部,肿瘤形状多不规则,小脑皮髓质同时受累,实质部分多分布性,10例为男性,发病年龄最大者为64岁。肿瘤实性部分与小脑灰质比较,T1WI为略低信号,T2WI为等或稍高信号。髓母NSE表达水平和强度显著高于正常人脑组织细胞瘤(P<0.01),17例髓母细胞瘤中NSE大部分呈强阳性表达。病理学显示光学显微镜下组织是原始的、未分化的肿瘤细胞,核梭形,形成许多菊形团瘤细胞。部分组织体积较小,向髓母细胞分化。局部分化为神经节细胞。结论:成人小脑髓母细胞瘤的MRI表现有一定的特征性,能够与其他小脑肿瘤相鉴别。NSE可作为小脑髓母细胞瘤的神经损伤指标。     

Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre,randomised, double-blinded trial

Purpose

Recent clinical data suggest that terlipressin, a vasopressin analogue, may be more beneficial in septic shock patients than catecholamines. However, terlipressin’s effect on mortality is unknown. We set out to ascertain the efficacy and safety of continuous terlipressin infusion compared with norepinephrine (NE) in patients with septic shock.

Methods

In this multicentre, randomised, double-blinded trial, patients with septic shock recruited from 21 intensive care units in 11 provinces of China were randomised (1:1) to receive either terlipressin (20–160 µg/h with maximum infusion rate of 4 mg/day) or NE (4–30 µg/min) before open-label vasopressors. The primary endpoint was mortality 28 days after the start of infusion. Primary efficacy endpoint analysis and safety analysis were performed on the data from a modified intention-to-treat population.

Results

Between 1 January 2013 and 28 February 2016, 617 patients were randomised (312 to the terlipressin group, 305 to the NE group). The modified intention-to-treat population comprised 526 (85.3%) patients (260 in the terlipressin group and 266 in the NE group). There was no significant difference in 28-day mortality rate between the terlipressin group (40%) and the NE group (38%) (odds ratio 0.93 [95% CI 0.55–1.56]; p?=?0.80). Change in SOFA score on day 7 was similar between the two groups: ??7 (IQR ??11 to 3) in the terlipressin group and ??6 (IQR ??10 to 5) in the NE group. There was no difference between the groups in the number of days alive and free of vasopressors. Overall, serious adverse events were more common in the terlipressin group than in the NE group (30% vs 12%; p?<?0.001).

Conclusions

In this multicentre, randomised, double-blinded trial, we observed no difference in mortality between terlipressin and NE infusion in patients with septic shock. Patients in the terlipressin group had a higher number of serious adverse events.

Trial registration

This trial is registered at ClinicalTrials.gov: ID NCT01697410.