A little trouble getting started: Initial slowness in Parkinson’s disease step negotiation

Bradykinesia is a prominent problem for persons with Parkinson’s disease (PD) and has been studied extensively with upper extremity tasks; however there is a lack of research examining bradykinesia in targeted lower extremity tasks related to mobility. Navigating steps and curbs are challenging tasks for older adults and neurologically impaired and thus utilizing these behaviors provides ecological validity to the study of bradykinesia. Herein we assess differences in step negotiation performance between individuals with PD and aged matched older adults. Three-dimensional kinematics and ground reaction forces were collected while 12 participants with PD and 12 older adults performed a single step up onto a platform. Persons with PD spent a significantly greater amount of time in the heel lift phase (P = 0.0003, d = 1.80). Peak vertical foot velocity of the lead foot was also significantly less in PD (P = 0.02, d = 1.05). Lastly, persons with PD displayed reduced sagittal hip and knee range of motion during the trail step (P = 0.01, d = 1.20 and P = 0.02, d = 1.05, respectively). Parkinson’s participants exhibited slight decrement in step negotiation execution. Increased step time and decreased foot velocity and range of motion were attributes associated with Parkinson’s step negotiation performance. Contrary to our hypothesis, in many comparisons, persons with PD during their best medicated state performed comparable to older adults, indicative of successful pharmacotherapy. Rehabilitation efforts can seek to improve performance in motor control tasks such as step negotiation, by restoring the relationship between perceived and actual motor output and enhancing muscle coordination and output as well as ranges of motion.     

Gadolinium-doped hollow CeO2-ZrO2 nanoplatform as multifunctional MRI/CT dual-modal imaging agent and drug delivery vehicle

Developing multifunctional nanoparticle-based theranostic platform for cancer diagnosis and treatment is highly desirable, however, most of the present theranostic platforms are fabricated via complicated structure/composition design and time-consuming synthesis procedures. Herein, the multifunctional Gd/CeO₂-ZrO₂/DOX-PEG nanoplatform with single nano-structure was fabricated through a facile route, which possessed MR/CT dual-model imaging and chemotherapy ability. The nanoplatform not only exhibited well-defined shapes, tunable compositions and narrow size distributions, but also presented a well anti-cancer effect and MR/CT imaging ability. Therefore, the Gd/CeO₂-ZrO₂/DOX-PEG nanoplatform could be applied for chemotherapy as well as dual-model MR/CT imaging.     

Paeoniflorin ameliorates symptoms of experimental Sjogren's syndrome associated with down-regulating Cyr61 expression

Paeoniflorin (PF), an active compound extracted from Paeony root, has been used in therapy of autoimmune diseases with effective clinical efficiency and higher safety. Sjogren's syndrome (SS) is a chronic, systemic, immune-mediated inflammatory disease. In this study, we demonstrated that novel pro-inflammatory factor Cyr61/CCN1 was up-regulated in epithelial cells of salivary glands of primary SS patients and submandibular gland autoantigen-induced experimental SS mice. Blocking Cyr61 expression with special monoclonal antibody improved saliva secretion by ameliorating inflammatory infiltration and cytokines production in vivo. Furthermore, we showed that PF could alleviate inflammation by down-regulating Cyr61 expression in experimental SS mice. In conclusion, our new findings revealed for the first time that Cyr61 involves the pathogenesis of primary SS and PF alleviates SS-like symptoms associated with inhibiting Cyr61 expression, providing new insights into the potential molecular mechanism of PF in primary SS treatment.     

Diagnosis and Management of Knee Osteoarthritis: Chinese Medicine Expert Consensus (2015)

Literature review shows that Chinese medicine and other related treatment are still the main stream treatment of knee osteoarthritis. Currently, there is short of handbook guiding Chinese medicine from evidence-based medical evidence, so it is a top priority to develop a clinical guideline from the expert consensus. After several rounds of discussion during the conference and examination by letter, which has collected opinions from nearly one hundred experts, consensus was reached. Nonpharmacologic interventions include health education, medical exercise, acupuncture, massage, acupotomology, and physiotherapy. Pharmacological interventions are as follows. Topical application includes fumigation, application, hot compressed, ironing and iontophoresis with Chinese herbs, etc. Chinese patent medicine for external use includes plaster, ointment, etc. Western medicine for external use mainly includes emulsion, ointment, plaster and embrocation containing nonsteroidal anti-inflammatory drugs (NSAIDs). Intraarticular injection mainly includes sodium hyaluronic acid, chitosan (for injection) with prudent use of glucocorticoid. Chinese herbal medicine and Chinese patent medicine can be taken referring to syndrome differentiation which mainly includes syndromes of qi stagnation and blood stasis, cold dampness, deficiency of Gan (Liver) and Shen (Kidney), deficiency of qi and blood. Western medicine mainly includes analgesic, NSAIDs, diseases modifying drugs. Surgery procedures mainly include joint irrigation, arthroscopic surgery, osteotomy, arthroplasty, etc.     

Hereditary angioedema in a Jordanian family with a novel missense mutation in the C1-inhibitor N-terminal domain

Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease caused by mutations in the SERPING1 gene. A Jordanian family, including 14 individuals with C1-INH-HAE clinical symptoms, was studied. In the propositus and his parents, SERPING1 had four mutations leading to amino acid substitutions. Two are known polymorphic variants (c.167T>C; p.Val34Ala and c.1438G>A; p.Val458Met), the others are newly described. One (c.203C>T; p.Thr46Ile) is located in the N-terminal domain of the C1-inhibitor protein and segregates with angioedema symptoms in the family. The other (c.800C>T; p.Ala245Val) belongs to the serpin domain, and derives from the unaffected father. DNA from additional 24 family members were screened for c.203C>T mutation in the target gene. All individuals heterozygous for the c.203C>T mutation had antigenic and functional plasma levels of C1-inhibitor below 50% of normal, confirming the diagnosis of type I C1-INH-HAE. Angioedema symptoms were present in 14 of 16 subjects carrier for the c.203T allele. Among these subjects, those carrying the c.800T variation had more severe and frequent symptoms than subjects without this mutation. This family-based study provides the first evidence that multiple amino acid substitutions in SERPING1 could influence C1-INH-HAE phenotype.     

Muscular co-contraction is related to varus thrust in patients with knee osteoarthritis

BackgroundPatients with knee osteoarthritis often present with varus thrust and muscular co-contraction during gait. It is unclear if these adaptations are related. The objective was to examine the relationship between muscle co-contraction and varus thrust during gait in patients with knee osteoarthritis and to determine if these relationships are modulated by disease severity or history of knee ligament rupture.MethodsParticipants (n = 42, 23 women, mean age 58 years) with knee osteoarthritis completed gait trials at self-selected speeds. Varus thrust was measured with an eight camera motion capture system sampled at 100 Hz. Co-contraction ratios were measured with surface electromyography sampled at 2000 Hz over the quadriceps, hamstrings, and gastrocnemius. Disease severity was measured on radiographs and history of anterior cruciate ligament rupture was confirmed on magnetic resonance imaging. Linear regression analyses examined the relationship between varus thrust and co-contraction ratios after controlling for radiographic disease severity and history of anterior cruciate ligament rupture.FindingsHigher vastus lateralis–lateral hamstring (b = 0.081, P < 0.001; R² = 0.353) and vastus medialis–medial hamstring (b = 0.063, P = 0.028; R² = 0.168) co-contraction ratios were associated with greater varus thrust. Quadriceps-gastrocnemius co-contractions ratios were not related to varus thrust (P > 0.05). Radiographic disease severity or history of anterior cruciate ligament injury did not significantly contribute to regression models.InterpretationGreater quadriceps-hamstring co-contraction is associated with greater varus thrust in patients with knee osteoarthritis. Potential explanations include increased co-contraction may provide stability or there is a proprioceptive reflex that is independent of any stabilizing role. Research is needed to test these hypotheses.     

喉鳞癌β-连环蛋白、细胞周期蛋白D1的表达与意义

目的探讨β-连环蛋白、细胞周期蛋白D1（Cyclin D1）在喉鳞癌的表达及其意义.方法采用免疫组织化学SP法检测58例喉鳞癌及10例正常喉上皮组织β-连环蛋白及Cyclin D1的表达.结果10例正常喉上皮β-连环蛋白表达位于细胞膜,细胞质未见表达;Cyclin D1均呈阴性表达.58例喉鳞癌组织中,31例β-连环蛋白细胞质表达,16例细胞核表达;34例Cyclin D1细胞核表达.pN＋的β-连环蛋白细胞质表达阳性率明显高于pN0（P＜0.05）,T3～T4喉癌病例中β-连环蛋白细胞质表达阳性率明显高于T1～T2喉癌病例（P＜0.05）;β-连环蛋白细胞质阳性表达与喉鳞癌部位、分化程度无关（P＞0.05）.Cyclin D1阳性表达仅与喉癌浸润程度相关（P＜0.05）,而与喉癌发生部位、分化程度、淋巴结转移无关（P＞0.05）.31例β-连环蛋白细胞质表达喉癌组织中23例Cyclin D1阳性表达,明显高于β-连环蛋白细胞膜表达者.结论喉鳞癌中β-连环蛋白表达可作为评估喉鳞癌恶性程度的重要生物学指标.     

不同条件对大鼠脑胶质瘤C6细胞HSP70表达的诱导

目的　探索和建立 SD大鼠胶质瘤细胞 (C6 ) HSP70蛋白表达最佳诱导条件。　方法　用 MTT法观察不同热休克条件和 /或药物诱导下 C6细胞生存率 ;用 FCM法检测 C6细胞膜 HSP70蛋白的表达。　结果　 (1) C6细胞在 4 2 ,4 3℃热休克 0～ 12 h的过程中 ,其生存率无明显影响。各种实验用药物 ,只要加上热休克 4 3℃ 2 h,对C6细胞的生存率的影响较单种药物同浓度要明显。 (2 ) C6细胞经 4 3℃热休克 1,2 ,4 ,6 ,8,10 ,12 ,14 ,16 ,2 0 ,2 4 h后 ,其胞膜 HSP70蛋白表达率均较对照组 (平均 4 .72 % )显著增高 (P<0 .0 5 ) ,其中 12 h表达率 (89.15 % )为最高 ,榄香烯 +热休克组又较其他各组高。　结论　一定条件下的热休克及某些药物可诱导 C6细胞膜 HSP70蛋白的表达 ,其中单因素以 4 3℃热休克 12 h表达率为最高 ,多因素以榄香烯 +43℃热休克 2 h表达率为最高