A combination therapy of massage and stretching increases parasympathetic nervous activity and improves joint mobility in patients affected by fibromyalgia

Objective: to investigate how therapeutic mas-sage, combined with stretching, can really con-tribute to the treatment of fibromyalgia (FM) symptoms. Design: Feasibility study. Setting: A single center. Participants: Twenty women having a preexisting diagnosis of FM based on American College of Rheumatology criteria were recruited. Intervention: Subjects received a total of 18 sessions of light massage administered by a physical therapist twice a week and then performed passive stretching exercises. Main out-come measures: heart rate (HR) and Heart Rate variability (HRV), the assessment of joint flexi-bility through elettrogoniometer, the Fibromyal-gia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI), and the Borg scale or Rating of Perceived exertion (RPE). Evalua-tions were conducted at the screening visit (T0), immediately at the end of the session of mas-sage (T1) and after completion of 18 sessions (T2). Results: HRV showed an improvement in terms of decreased sympathetic tone and in-crease of parasympathetic tone at the end of treatment. Also joint flexibility showed a sig-nificant improvement at T2 compared with the screening. FIQ, PSQI, RPE did not change. Conclusions: the findings highlight the excellent compliance of FM patients to the combined therapy of massage and stretching, showing an amelioration of muscle stiffness and an improvement of autonomic nervous system with a decrease of sympathetic tone and an increase of parasympathetic tone. The questionnaires did not show any ameliorations, probably because in these patients the perception of quality of life is distorted compared with more objective pa-rameters, such as muscle rigidity, the articular mobility and the autonomic nervous system.

Kv7 channels a potential therapeutic target in fibromyalgia: A hypothesis

Fibromyalgia is characterized by the primary symptomsof persistent diffuse pain, fatigue, sleep disturbance and cognitive dysfunction. Persistent pain conditions, such as fibromyalgia, are often refractory to current available therapies. An involvement of K^+ channels in the pathophysiology of fibromyalgia is emerging and supported by drug treatments for this condition exhibiting action at these molecular processes. K^+ channels constitute potential novel target candidates for pain therapy offering peripheral and/or central actions. The Kv7 channel activators, flupirtine and retigabine, have exhibited pharmacological profiles compatible to the requirements needed for use as a therapeutic approach to fibromyalgia. Clinical trials to address the multidimensional challenges of fibromyalgia with flupirtine and retigabine will provide important insight to the role of K^+ channels in this condition.

Role of Cognitive Behavioral Therapy in Fibromyalgia: A Systematic Review

A literature search of articles from 2002-2019 was performed using Medline, Embase, Cochrane, LILACS, IBECS, CRD, and Epistemonikos databases, to analyze the effects of Cognitive-Behavioral Therapy (CBT) in the treatment of fibromyalgia. Twenty-seven articles were selected in which CBT was performed exclusively by specialist physicians, associated or not with conventional pharmacological treatment and/or physical exercise. In most articles, CBT worked with self-knowledge and cognitive restructuring, attempting to reduce pain perception, and it showed a general improvement in daily activities by decreasing patient’s limitations, such as morning stiffness. The literature showed significant correlations of CBT in pain processing over time. When CBT was compared to conventional pharmacological therapy, a certain superiority of CBT could be observed concerning the quality of life, catastrophizing, and acceptance of pain. However, when they were simultaneously applied, this improvement in quality of life was not observed.

纤维肌痛综合征生物标记物的筛选及免疫细胞浸润分析

背景:纤维肌痛综合征作为常见风湿病,其发病与中枢敏化及免疫异常有关,但具体过程尚未阐明,缺乏特异性诊断标志物,不断探索该病的发病机制具有重要的临床意义。目的:基于加权基因共表达网络分析(WGCNA)等生物信息学方法和机器学习算法筛选纤维肌痛综合征潜在的诊断相关标志基因,并分析其免疫细胞浸润特征。方法:对来自基因表达综合数据库(GEO)的纤维肌痛综合征数据集转录谱进行差异分析和WGCNA分析,整合筛选出差异共表达基因,进一步采用机器学习套索回归(LASSO)算法、支持向量机递归特征消除(SVM-RFE)机器学习算法来识别核心生物标志物,并绘制受试者工作特征(ROC)曲线以评估诊断价值。最后,采用单样本基因集富集分析(ssGSEA)和基因集富集分析(GSEA)评估纤维肌痛综合征的免疫细胞浸润情况及通路富集。结果与结论:①对GSE67311数据集按照log2|(FC)|>0,P<0.05的条件进行差异分析后获得8个下调的差异表达基因;进行WGCNA分析后获得正相关性最高(r=0.22,P=0.04)的模块(MEdarkviolet)内含基因497个,负相关性最高(r=-0.41,P=6×10-5)的模块(MEsalmon2)内含基因19个;将差异表达基因与WGCNA的2个高相关性模块基因取交集,获得7个基因。②对上述7个基因进行LASSO回归算法筛选出4个基因,进行SVM-RFE机器学习算法筛选出5个基因,两者取交集后确定了3个核心基因,分别为重组1号染色体开放阅读框150蛋白(germinal center associated signaling and motility like,GCSAML)、整合素β8(Integrin beta-8,ITGB8)和羧肽酶A3(carboxypeptidase A3,CPA3);绘制3个核心基因的ROC曲线下面积分别为0.744,0.739,0.734,提示均具有很好的诊断价值,可作为纤维肌痛综合征的生物标志物。③免疫浸润分析结果显示,与对照组相比纤维肌痛综合征患者记忆B细胞、CD56 bright NK细胞和肥大细胞显著下调(P<0.05),且与上述3个生物标志物显著正相关(P<0.05)。④富集分析结果提示,纤维肌痛综合征的富集途径包括9条,主要与嗅觉传导、神经活性配体-受体相互作用及感染等通路密切相关。⑤上述结果显示,纤维肌痛综合征的发生发展与多基因参与、免疫调节异常及多个通路失调有关,但这些基因与免疫细胞之间的相互作用,以及它们与各通路之间的关系尚需进一步研究。

Multi-scale Distribution Pattern of Natural Ramet Population in the Rhizomatous Herb ,Thermopsis lanceolata

Thedistributionpatternofnaturalrametpopulationintherhizomatousherb ,Thermopsislanceolata R .Br.,at 5scales (0 .2m ,0 .4m ,0 .6m ,0 .8mand 1.0m)wasinvestigatedusinggridsamplingand spatialauto_correlationanalysis (Moran’sI)inMaowususandlandofInnerMongoliaofChina .Theresult showedthattherametpopulationhadnon_randomdistributionpatternatfourscales (0 .2m ,0 .4m ,0 .6m and 1.0m) .Themostfrequentlyobservedpatternwascontagiousatthescaleof 0 .2m .Thegenethadsym podialgrowthandnearlyphalanxarchitecture .Thebranchingangleoftherhizomeswasfrom 10°to 30° .The densityoftherametpopulationwasfrom 35to 131ramets·m- 2 .Themeanheightoframetswasbetween 11.0 cmand 2 5.9cm .Thebiomassoftherametpopulationwas 2 6 3.6 3g·m- 2 and 30 6 .19g·m- 2 inthetwo plots,respectively .33.71%and 4 4 .97%ofthebiomassallocationtorhizomeswereobservedandthe biomassallocationtorootswas 2 9.91%and 2 9.95%andthattoleaveswas 2 5.12 %and 36 .35%inthetwo plots ,respectively .Theratioofroottoshootwas 0 .4 4inbothplotswhiletheratioofbelow_toabove_ground biomasswas 2 .12and 3.59,respectively .

Effects of oral tacrolimus as a rapid induction therapy in ulcerative colitis

AIM:To determine the efficacy and safety of rapid induction therapy with oral tacrolimus without a meal in steroid-refractory ulcerative colitis(UC)patients.METHODS:This was a prospective,multicenter,observational study.Between May 2010 and August 2012,49 steroid-refractory UC patients(55 flare-ups)were consecutively enrolled.All patients were treated with oral tacrolimus without a meal at an initial dose of 0.1mg/kg per day.The dose was adjusted to maintain trough whole-blood levels of 10-15 ng/m L for the first 2 wk.Induction of remission at 2 and 4 wk after tacrolimus treatment initiation was evaluated using Lichtiger’s clinical activity index(CAI).RESULTS:The mean CAI was 12.6±3.6 at onset.Within the first 7 d,93.5%of patients maintained high trough levels(10-15 ng/m L).The CAI significantly decreased beginning 2 d after treatment initiation.At 2wk,73.1%of patients experienced clinical responses.After tacrolimus initiation,31.4%and 75.6%of patients achieved clinical remission at 2 and 4 wk,respectively.Treatment was well tolerated.CONCLUSION:Rapid induction therapy with oral tacrolimus shortened the time to achievement of appropriate trough levels and demonstrated a high remission rate 28 d after treatment initiation.Rapid induction therapy with oral tacrolimus appears to be a useful therapy for the treatment of refractory UC.

Hybrid vs sequential therapy for eradication of Helicobacter pylori in Taiwan: a prospective randomized trial

AIM: To evaluate the efficacy of sequential vs hybrid therapy in patients with Helicobacter pylori(H. pylori) infection.METHODS: From March 2013 to May 2014,one hundred and seventy-five H. pylori infected patients who had not been treated for H. pylori before wererandomized to receive either sequential therapy(rabeprazole 20 mg and amoxicillin 1 g twice daily for 5 d,followed by rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg twice daily for 5 d) or hybrid therapy(rabeprazole 20 mg and amoxicillin 1 g for 7 d,followed by rabeprazole 20 mg,amoxicillin 1 g,clarithromycin 500 mg and metronidazole 500 mg twice daily for 7 d). H. pylori status was confirmed by positive results of both rapid urease test and histology examination or a positive result of culture. Eradication efficacy was assessed by follow-up endoscopy with rapid urease test and histological examination 8 wk after the end of anti-H. pylori therapy,or 13C-urea breath test at least 4 wk after completion of treatment. The primary outcome was H. pylori eradication by intension-to-treat(ITT) and per-protocol(PP) analyses.RESULTS: One hundred and sixty-seven patients(83 patients in the sequential group and 84 patients in the hybrid group) completed the study. The compliance rates were 97.6% and 97.7% for the two groups,respectively. The eradication rate was 78.2% for the sequential group and 92% for the hybrid group by ITT analysis(P = 0.01). The eradication rate was 81.9% for the sequential group and 96.4% for the hybrid group by PP analysis(P = 0.01). Univariate analysis for the clinical and bacterial factors did not identify any risk factors associated with treatment failure. Severe adverse events were observed in 2.3% of patients in the sequential group and 2.4% of those in the hybrid group.CONCLUSION: Due to a grade A(> 95%) success rate for H. pylori eradication by PP analysis,similar compliance and adverse events,hybrid therapy seems to be an appropriate eradication regimen in Taiwan.

Pramipexole, a dopamine D3/D2 receptor-preferring agonist, attenuates reserpine-induced fibromyalgia-like model in mice

Fibromyalgia(FM) is a complex pathology described as persistent hyperalgesia including somatic and mood dysfunctions, depression and anxiety. Although the etiology of FM is still unknown, a significant decrease in biogenic amines is a common characteristic in its pathogenesis. Here, our main objective was to investigate the role of dopamine D3/D2 receptor during the reserpine-induced pain in mice. Our results showed that pramipexole(PPX) – a dopaminergic D3/D2 receptor agonist – inhibited mechanical allodynia and thermal sensitivity induced by reserpine. Relevantly, PPX treatment decreased immobility time and increased the number of grooming in the forced swimming test and splash test, respectively. Animals that received PPX remained longer in the open arms than the reserpine group using elevated plusmaze apparatus. The repeated PPX administration, given daily for 4 days, significantly blocked the mechanical and thermal allodynia during FM model, similarly to pregabalin, although it failed to affect the reserpine-induced thermal nociception. Reserpine administration induced significant downregulation of dopamine concentration in the central nervous system, and repeated treatment with PPX restored dopamine levels in the frontal cortex and spinal cord tissues. Moreover, PPX treatment inhibited oxidants production such as DCFH(2′,7′-dichlorodihydrofluorescein) and nitrite, also decreased oxidative damage(carbonyl), and upregulated the activity of superoxide dismutase in the spinal cord. Together, our findings demonstrated the ability of dopamine D3/D2 receptor-preferring agonist in reducing pain and mood dysfunction allied to FM in mice. All experimental protocols were approved by the Universidade Federal de Santa Catarina(UFSC) Ethics Committee(approval No. 2572210218) on May 10, 2018.

Thermal Fatigue Behaviour of Co-Based Alloy Coating Obtained by Laser Surface Melt-Casting on High Temperature Alloy

A thermal fatigue behaviour of Co-based alloy coating obtained by laser surface meltcasting on the high temperature alloy GH33 was studied.The results show that after each time of thermal cycling,the final residual stress was formed in the melt-casting layer which is attributed to the thermal stress and structural stress.Through the first 50 times of thermal cycling,the morphology of coating still inherits the laser casting one,but the dendrites get bigger;After the second 50 times of thermal cycling,corrosion pits emerge from coating,and mostly in the places where coating and substrate meet.The fatigue damage type of coating belongs to stress corrosion.

SYNTHESIS AND THERMAL STABILITY OF NANOCOMPOSITE nc-TiN/a-TiB_2 THIN FILMS

Several nc-TiN/a-TiB2 thin films comprised of nanocrystalline (nc-) TiN and amor phous (a-) TiB2 phases were deposited on Si(100) at room temperature by reactive unbalanced dc magnetron sputtering, followed by vacuum annealed at 400, 600, 80 0 and 1000℃ for 1h, respectively. Effects of B content on microstructure, mecha nical behaviors and thermal microstructure stability have been investigated by X -ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and nanoindentation measurements. The results indicated that B addition greatly affected both microstructure and mechanical behavior of nc-Ti N/a-TiB2 thin films. With increasing B content the grain size decreased. A maxim um hardness value of about 33GPa was obtained at B content of about 19at.%. The improved mechanical properties of nc-TiN/a-TiB2 films with the addition of B int o TiN were attributed to their densified microstructure with development of fine grain size. Only addition of sufficient B could restrain grain growth during an nealing. High B content resulted in high microstructure stability. The crystalli zation of amorphous matrix occurred at about 800℃, forming TiB or TiB2 crystall ite, depending on B content. Before that no change in bonding configuration was found.

The Impact of Fibromyalgia on Daily Women: A Contribution to Nursing Assistants

Objective: To evaluate the impact of fibromyalgia in daily and associated factors in women treated at the polyclinic in Paraná. Method: A descriptive, cross-sectional study was conducted with individualized data for 52 women ≥ 50 years from the policlinic of the Curitiba of Paraná State, Brazil. Data were collected an online survey and the quality of life was assessed by one specific instrument, the Fibromyalgia Impact Questionnaire (FIQ). Verbal or written informed consent was obtained from all participants. Results: A total of 157 patients completed the survey. The average age was approximately 50 years (range 29 - 77 years). The most frequent comorbidities were depression (61.5%) and (19%) arthrosis. Conclusion: The understanding of the commodities associated with fibromyalgia helps health professionals to reach the patient efficiently in their orientations about nursing care in women with fibromyalgia.

THERMAL DECOMPOSITION BEHAVIOR OF AMMONIUM THIO TUNGSTATE in H_2

The ther m al deco m position mechanism of a m m oniu m thiotungstate of the size of 63 ～75 μmin H2 has been investigated by D T A and X R D methods . The ther m al deco m position activationenergies and the orders of a m m oniu m thiotu ngstate were calculated by means of Kissinger , Freem an Carroll and Coast Redfern m ethods . It w as also obtained that therm al deco m posi tion is cond ucted according to four reaction equations :( N H4) 2 W S4· H2 O(s) ( N H4) 2 W S4(s) + H2 O(g) W S2(s) + 2 N H3(g) + H2(g) + 2 S(s) + H2 O(g) W S2(s) + 2 N H3(g) + 2 H2 S(g) + H2 O(g) W S2(s) + W(s) + 2 N H3(g) + 2 H2 S(g) + H2 O(g) .

CXC chemokines and chemokine receptors in gastric cancer: From basic findings towards therapeutic targeting

Gastric cancer is the fourth most common cancer,and the second-highest cause of cancer-related deaths worldwide.Despite extensive research to identify novel diagnostic and therapeutic agents,patients with advanced gastric cancer suffer from a poor quality of life and poor prognosis,and treatment is dependent mainly on conventional cytotoxic chemotherapy.To improve the quality of life and survival of gastric cancer patients,a better understanding of the underlying molecular pathologies,and their application towards the development of novel targeted therapies,is urgently needed.Chemokines are a group of small proteins associated with cytoskeletal rearrangements,the directional migration of several cell types during development and physiology,and the host immune response via interactions with G-protein coupled receptors.There is also growing evidence to suggest that chemokines not only play a role in the immune system,but are also involved in the development and progression of tumors.In gastric cancer,CXC chemokines and chemokine receptors regulate the trafficking of cells in and out of the tumor microenvironment.CXC chemokines and their receptors can also directly influence tumorigenesis by modulating tumor transformation,survival,growth,invasion and metastasis,as well as indirectly by regulating angiogenesis,and tumor-leukocyte interactions.In this review,we will focus on the roles of CXC chemokines and their receptors in the development,progression,and metastasis of gastric tumors,and discuss their therapeutic potential for gastric cancer.

Simultaneous modulated accelerated radiation therapy for esophageal cancer:A feasibility study

AIM: To establish the feasibility of simultaneous modulated accelerated radiation therapy (SMART) in esophageal cancer (EC).

Emerging pharmacological strategies for the treatment of fibromyalgia

Fibromyalgia(FM) has been described as a chronic clinical condition related to multisensory hypersensitivitypresenting with a complex of symptoms dominated by chronic widespread pain associated with the existence of a range of co-morbidities, such as fatigue, sleep disturbance, cognitive impairment, anxiety and depression. Current treatments include drugs that target serotonin and noradrenaline levels within the central nervous system, e.g., tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, and voltage-gated calcium channel subunit ligands, e.g., gabapentin and pregabalin. Investigation of a range of novel targets, such as melatoninergic, cannabinoid, dopamine, NMDA, angiotensin, orexin and opioid receptors, and ion channels, in addition revisiting bioamine modulation and subunits has provided efficacy outcomes that improve the health status of patients with FM. Nevertheless, modest and limited efficacy is often observed reflecting the heterogeneity of FM with existence of subpopulations of patients, the contribution of peripheral and central components to the pathophysiology, and the extensive range of accompanying co-morbidities. The complexity and multidimensional nature of FM is emphasized by the diversity of pharmacological targets gaining interest. Clues to underlying mechanisms which offer themselves as novel and potential targets for new medications are being provided by advances in the understanding of the pathophysiology of FM.

Frequency and prognostic role of mucosal healing in patients with Crohn's disease and ulcerative colitis after one-year of biological therapy

AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn&#x02019;s disease (CD) and ulcerative colitis (UC).

Forgiveness education in fibromyalgia: A qualitative inquiry

The purpose of this qualitative study was to assess perspectives on the acceptability and the potential applicability of a forgiveness education in patients with fibromyalgia. The concept and tools of forgiveness were presented to thirteen women (age: 40 - 54 years) with a previous diagnosis of fibromyalgia. Subjects participated in 1 of 2 focus groups following a 90-minute education session in which forgiveness was presented as an emotion-focused coping strategy to deal with interpersonal stressors. Qualitative assessment of focus group discussions reveals 3 themes: 1) forgiveness is healthy and reduces pain, 2) forgiveness is within a patient’s personal control, and 3) forgiveness education is similar to other types of patient education and is well received. Our results suggest that forgiveness education is acceptable and feasible in patients with fibromyalgia. This justifies further exploration of forgiveness as an emotion-focused self- management strategy to decrease psychological distress.

Orofacial pain and fibromyalgia pain:Being aware of comorbid conditions

Orofacial pain originating from myofascial pain of temporomandibular disorders is the second most common source of pain, after tooth pain. However, diagnosis of myofascial pain is challenging due to its characteristic referral pattern. Furthermore, pain arising from structures in the orofacial region may be a presentation of fibromyalgia and treatment directed at temporomandibular disorders fails to alleviate the pain. Similarly, patients with fibromyalgia may present with pain in the orofacial region. The physician in this case should be aware of temporomandibular disorders, its characteristic findings and treatment approaches that might be included in the treatment plan.

Association of COL1A1 rs180012 SNP and Fibromyalgia Suggests the Implication of Collagen Structure in Musculoskeletal Pain

Fibromyalgia (FM) is a complex, chronic condition, which causes widespread musculoskeletal pain, fatigue and a variety of other symptoms. Many polymorphisms related to neuroendocrine system function as the ApoE isoforms, Val158Met polymorphism in COMT, as well as a 44 bp deletion located in 5-HTTLPR, have been studied. Other polymorphisms have been related to inflammatory response such as the 70 bp VNTR in IL-4 or to citokine levels. Furthermore, some studies focused on finding out new FM related SNPs, have been performed by genome wide association scan (GWAS). The target of this work was to study a possible linkage of a collagen type I polymorphism (COL1A1 rs180012 SNP) affecting bone mineralization, with fibromyalgia. Results obtained show a clear association of ss homozygous genotype with FM patients no dependent on bone mineralization.

Early-Stage Juvenile Fibromyalgia in a 12-Year-Old Girl

Juvenile fibromyalgia (JFM) is often diagnosed at a later stage. Therefore, little is known about its early phase. A 12-year-old girl with persistent lumbago without fever consulted an orthopedist, but imaging studies showed no abnormalities and analgesics were ineffective. She therefore visited our pediatric clinic. On digital palpation, she had pain in 13 of the 18 tender point sites of fibromyalgia. The blood test results were unremarkable. A medical interview revealed character tendencies often seen in patients with JFM;she was serious-minded, uncompromising, and showed excessive concern for others. Furthermore, psychological stress for the approaching annual sports day might have built up. All factors considered, early-stage JFM was the probable diagnosis. The patient accepted the diagnosis and understood that the disease may be psychogenic. Getting through the sports day cured her symptoms. This case highlights the importance of initial care, including a detailed explanation, in those with JFM.