Comparison of the placebo effect between different non-penetrating acupuncture devices and real acupuncture in healthy subjects: a randomized clinical trial

Background

Several studies have used placebo acupuncture methods in recent years as a way for blinding therapeutic effect of acupuncture, however placebo method selection has not followed enough methodological criteria to the point of stabilishing a consensus of what should be the best method to be used. This study aimed to evaluate the effectiveness of three different placebo acupuncture methods for blinding applied in healthy subjects.

Methods

This study was approved by the Ethics Committee of the Federal University of Sergipe with the number 47193015.5.0000.5546 and all individuals participating in the study signed a free and informed consent. For this study, 321 healthy volunteers were randomly divided into seven groups using the abdominal point stomach (ST) 25 and seven groups using the lumbar point bladder (Bl) 52 for stimulation. For real acupuncture procedure, three different methods of placebo acupuncture plus a mix between real acupuncture and placebo applied in the same individual, totaling fourteen groups in this study. Outcome assessments were performed before and immediately after applying the technique. Investigator who assessed variables had no knowledgement about the method was applied. Identification, weight and height were measured before puncture by using. At the end, subjects were asked if they believed they were receiving real or placebo acupuncture.

Results

There was no significant difference between groups for the perception about the type o stimulation (wheter real or placebo puncture). Percentage of subjects who reported to have received real acupuncture in the abdominal point was 69.56% in real group, 86.95% in group Park Sham, 82.60% in needle?+?foam, 91.30% in insertion and removal, 78.26% in real?+?Park Sham, 86.36% in real?+?needle and foam, 86.95% in real?+?insertion and removal, and for the lumbar point was 86.36% in real group, 86.95% in group Park Sham, 69.56% in needle?+?foam, 72% in insertion and removal, 86.95% in real?+?Park Sham, 81.81% in real?+?needle and foam and 78.26% in real?+?insertion and removal.

Conclusion

All placebo acupuncture methods proposed in this study were equally effective for bliding the study participants using either abdominal or lumbar acupoints, and none of the placebo methods presented benefit compared to the other to be used in future clinical trials.

Ethics Committee

Federal University of Sergipe (UFS), number of approval: 47193015.5.0000.5546

Trial registration

ensaiosclinicos.gov.br RBR-3w2p32 Registered in 28th January 2016.

     

A donor splice site mutation in <Emphasis Type="Italic">CISD2</Emphasis> generates multiple truncated,non-functional isoforms in Wolfram syndrome type 2 patients

Background

Mutations in the gene that encodes CDGSH iron sulfur domain 2 (CISD2) are causative of Wolfram syndrome type 2 (WFS2), a rare autosomal recessive neurodegenerative disorder mainly characterized by diabetes mellitus, optic atrophy, peptic ulcer bleeding and defective platelet aggregation. Four mutations in the CISD2 gene have been reported. Among these mutations, the homozygous c.103?+?1G?>?A substitution was identified in the donor splice site of intron 1 in two Italian sisters and was predicted to cause a exon 1 to be skipped.

Methods

Here, we employed molecular assays to characterize the c.103?+?1G?>?A mutation using the patient’s peripheral blood mononuclear cells (PBMCs). 5′-RACE coupled with RT-PCR were used to analyse the effect of the c.103?+?1G?>?A mutation on mRNA splicing. Western blot analysis was used to analyse the consequences of the CISD2 mutation on the encoded protein.

Results

We demonstrated that the c.103?+?1G?>?A mutation functionally impaired mRNA splicing, producing multiple splice variants characterized by the whole or partial absence of exon 1, which introduced amino acid changes and a premature stop. The affected mRNAs resulted in either predicted targets for nonsense mRNA decay (NMD) or non-functional isoforms.

Conclusions

We concluded that the c.103?+?1G?>?A mutation resulted in the loss of functional CISD2 protein in the two Italian WFS2 patients.

     

Temporal lobe anatomy: eight imaging signs to facilitate interpretation of MRI

Purpose

The temporal lobe is anatomically and functionally complex. However, relatively few radiologic signs are described to facilitate recognition of temporal lobe sulci and gyri in clinical practice. We devised and tested 8 radiologic signs of temporal lobe anatomy.

Methods

Images from volumetric magnetization-prepared rapid gradient-echo imaging were analyzed of 100 temporal lobes from 26 female and 24 male patients. Patient age ranged from 1 to 79 years (mean 19 years; standard deviation 16 years). Standardized axial, coronal, and sagittal planes were evaluated and cross-referenced. Eight signs to delineate the superior temporal gyrus, Heschl gyrus (HG), parahippocampal gyrus, rhinal sulcus, collateral sulcus proper, or the occipitotemporal sulcus, or a combination, were evaluated in the sagittal or axial plane. Two neuroradiologists independently evaluated each sign; the sign was considered present only with positive reader agreement.

Results

All 8 signs were present in most patients. The most frequent signs were the posterior insular corner to identify HG in the axial plane (100 %), pointed STG to identify STG in the axial plane (98 %), and parahippocampal Y to identify the posterior parahippocampal gyrus in the sagittal plane (98 %). The frequencies were similar between the right and left cerebral hemispheres.

Conclusions

Temporal lobe gyri and sulci can be reliably identified in multiple planes using anatomic signs.

     

<Emphasis Type="Italic">Helicobacter bilis</Emphasis>-Associated Suppurative Cholangitis in a Patient with X-Linked Agammaglobulinemia

?

Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases.

Purpose

We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis.

Methods

16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis.

Results

Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin.

Conclusion

In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.

     

Glücklich als Paar – glücklicher Schlaf?

Background

Millions of people share a bed with their partner. Sleep und relationship could possibly influence each other.

Objectives

To identify and discuss connections between relationship and sleep quality.

Methods

Review of the literature in electronic databases.

Results

Conflict and violence in relationships lead to decreases in both partners’ sleep quality. Constructive approaches to resolving conflicts is necessary for good sleep, and vice versa. Women prefer partners with sleep-wake rhythms matching their own and report higher relationship satisfactions when the couple’s chronotypes are compatible.

Conclusions

Sleep and circadian rhythms play important roles in relationships. When treating insomnia, the relationship and the partner’s sleep should be taken into account.

     

Ethical Assessment of Human Embryonic Stem Cell Research According to Turkish Muslim Scholars: First Critical Analysis and Some Reflections

Background

Turkey, with a Muslim population of officially over 99 %, is one of the few secular states in the Muslim world. Although state institutions are not based on Islamic juridical and ethical norms, the latter play a significant role in defining people’s attitudes towards controversial issues in the modern world, especially when backed by opinions of Muslim scholars living in Turkey. Accordingly, opinions of Muslim scholars undoubtedly have an important effect on bioethical decisions made by institutions and individuals.

Objective(s)

To explore the ethical positions of Muslim scholars living in Turkey and their arguments used in the ethical assessment of embryonic stem cell research; to discuss the biological-moral tensions arising in medical research on human embryos.

Design

Qualitative study.

Setting

Muslim scholars located in different parts of Turkey.

Methods

Qualitative method, involving the collection of opinions of various scholars, by means of 15 individual semi-structured interviews, evaluated using thematic qualitative analysis.

Results

Positions regarding embryonic stem cell research differ among Muslim scholars in Turkey. On the other hand, even where positions are similar, they are often supported by different arguments.

Conclusion

Despite the heterogeneity of the arguments presented, the dominant position considers embryonic stem cell research as morally acceptable.

     

A comparison of multiple imputation methods for missing data in longitudinal studies

Background

Multiple imputation (MI) is now widely used to handle missing data in longitudinal studies. Several MI techniques have been proposed to impute incomplete longitudinal covariates, including standard fully conditional specification (FCS-Standard) and joint multivariate normal imputation (JM-MVN), which treat repeated measurements as distinct variables, and various extensions based on generalized linear mixed models. Although these MI approaches have been implemented in various software packages, there has not been a comprehensive evaluation of the relative performance of these methods in the context of longitudinal data.

Method

Using both empirical data and a simulation study based on data from the six waves of the Longitudinal Study of Australian Children (N?=?4661), we investigated the performance of a wide range of MI methods available in standard software packages for investigating the association between child body mass index (BMI) and quality of life using both a linear regression and a linear mixed-effects model.

Results

In this paper, we have identified and compared 12 different MI methods for imputing missing data in longitudinal studies. Analysis of simulated data under missing at random (MAR) mechanisms showed that the generally available MI methods provided less biased estimates with better coverage for the linear regression model and around half of these methods performed well for the estimation of regression parameters for a linear mixed model with random intercept. With the observed data, we observed an inverse association between child BMI and quality of life, with available data as well as multiple imputation.

Conclusion

Both FCS-Standard and JM-MVN performed well for the estimation of regression parameters in both analysis models. More complex methods that explicitly reflect the longitudinal structure for these analysis models may only be needed in specific circumstances such as irregularly spaced data.

     

Deficiencies in elements involved in TLR4-receptor signalling in RBL-2H3 cells

Objective

RBL-2H3 cells express Toll-like receptors, including TLR4. This study aims to assess various aspects of the TLR4 pathway.

Methods

RBL-2H3 cells were indirectly stained for cell surface TLR4, 25 CD14 and intracellular MyD88 proteins and analysed through flow cytometry for single-colour staining.

Results

While TLR4-receptors are expressed in RBL-2H3 cells, associated elements involved in the signaling pathway, CD14 and MyD88, are not.

Conclusion

Care should be taken if RBL-2H3 cells are used to study aspects of the innate immune system in mast cells.

     

Picture perfect—how seeking perfection influences sleep and romantic relationships

Background

Studies have shown that sleep quality is negatively affected by perfectionism. Moreover, partner- or relationship-oriented perfectionism negatively influences relationship quality.

Objective

This paper aims to investigate the association of general perfectionism with sleep quality and relationship quality.

Materials and methods

A study assessing perfectionism, sleep quality, and relationship quality was performed via analyzing online questionnaires completed by 489 German adults from the general population.

Results

Participants with impaired sleep showed a higher level of maladaptive perfectionism (concern over mistakes and doubts, parental expectations, and criticism) than participants with good sleep, whereby the severity of sleep problems was not determining. Relationship quality is affected by perfectionism. However, this association is mediated by sleep quality.

Conclusion

Perfectionism is associated with worse sleep quality but not with worse relationship quality when sleep quality is integrated into the model as a mediator.

     

Evaluation of quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging in qualitative diagnosis of hepatic masses

Background

To explore the value of parameters of multiphase dynamic contrast-enhanced magnetic resonance imaging (MDCE-MRI) in the qualitative diagnosis of hepatic masses.

Methods

Eighty patients with hepatic masses were retrospectively analyzed. All the patients underwent MDCE-MRI at 3.0?T MR before treatment. Mean enhancement time (MET), positive enhancement integral (PEI), a maximum slope of increase (MSI), and a maximum slope of decrease (MSD) were measured.

Results

There were significant differences between benign and malignant hepatic masses with respect to MET, PEI, and MSI values. The PEI and MSI values between hemangiomas, hepatocellular carcinomas (HCCs), cholangiocarcinomas, and metastatic tumors had significant differences. The MSD value between metastatic tumors, HCCs, and hemangiomas were significantly different. The area under the curve (AUC) values of the receiver operator characteristic curves for MET, PEI, and MSI were 0.70, 0.72, and 0.80, respectively. The specificity of MET, PEI, and MSI were all 77%, and the sensitivities of MSI was the highest, of which was 82.40%. Logistic regression analysis showed the regression equation to be P?=?1/[1?+?e^{0.008?×?1?+?0.007?×?2–6.707}], and taking the Youden index maximum points as a diagnostic point was 0.2946.

Conclusion

Some parameters of MDCE-MRI have significant roles in differentiating hepatic masses.

     

Micronized palmitoylethanolamide reduces joint pain and glial cell activation

Objective and design

Temporomandibular disorder (TMD) is a common painful condition in the temporomandibular joint (TMJ). Joint inflammation is believed to be a chief cause of pain in patients with TMD, through the release of pro-inflammatory cytokines that induce peripheral sensitization of nerve terminals followed by microglial stimulation.

Materials and subject

TMJ was induced in rats with the injection of complete Freund’s adjuvant (CFA) emulsion into the left TMJ capsule.

Treatment

The present study would assess the effects of micronized palmitoylethanolamide (m-PEA) on glial activation and trigeminal hypersensitivity.

Methods

Ten mg/kg m-PEA or corresponding vehicle was administered 1 h after CFA and mechanical allodynia and edema were evaluated at 24 and 72 h after CFA injection.

Results

CFA-injected animals showed TMJ edema and ipsilateral mechanical allodynia accompanied by a robust growth in GFAP protein-positive satellite glial cells and activation of resident macrophages in the TG. Moreover, m-PEA administration significantly reduced the degree of TMJ damage and pain, macrophage activation in TG and up-regulation of Iba1.

Conclusions

The results confirm that m-PEA could represent a novel approach for monitoring pain during trigeminal nerve sensitization.

     

Histamine intolerance: a metabolic disease?

Objective

To evaluate the evidence regarding the disease concept of histamine intolerance as a state of inadequate histamine inactivation.

Methods

Keyword-based systematic screening of the scientific literature and of public websites focusing on diagnostic and therapeutic procedures.

Results

Histamine intolerance is commonly diagnosed based solely on subjective reporting of symptoms instead of following systematic diagnostic procedures based on objective laboratory and physical parameters. The only effective long-term therapy is avoidance of histamine-containing food.

Conclusions

The concept of histamine intolerance as a metabolic disease is in need of more experimental and clinical evidence and affected patients will benefit from a clear, evidence-based diagnostic and therapeutic regime.

     

Baicalin promotes apoptosis and inhibits proliferation and migration of hypoxia-induced pulmonary artery smooth muscle cells by up-regulating A2a receptor via the SDF-1/CXCR4 signaling pathway

Background

Baicalin is a flavonoid compound that exerts specific pharmacological effect in attenuating the proliferation, migration, and apoptotic resistance of hypoxia-induced pulmonary artery smooth muscle cells (PASMCs). However, the underlying mechanism has not been fully elucidated yet. Although our previous studies had indicated that activation of A2aR attenuates CXCR expression, little is known about the relationship between A2aR and SDF-1/CXCR4 axis in hypoxic PASMCs. In this study, we aimed to investigate the effect of A2aR on the SDF-1/CXCR4 axis in hypoxic PASMCs, the mechanism underlying this effect, and whether baicalin exerts its protective functions though A2aR.

Methods

Rat PASMCs were cultured under normoxia/hypoxia and divided into nine groups: normoxia, hypoxia, hypoxia + AMD3100 (a CXCR4 antagonist), hypoxia + baicalin, hypoxia + negative virus, normoxia + A2aR knockdown, hypoxia + A2aR knockdown, hypoxia + CGS21680 (an A2aR agonist), and hypoxia + A2aR knockdown + baicalin. Lentiviral transfection methods were used to establish the A2aR knockdown model in PASMCs. Cells were incubated under hypoxic conditions for 24 h. Expression levels of A2aR, SDF-1, and CXCR4 were detected using RT-qPCR and western blot. The proliferation and migration rate were observed via CCK-8 and Transwell methods. Cell cycle distribution and cell apoptosis were measured by flow cytometry (FCM) and the In-Situ Cell Death Detection kit (Fluorescein).

Results

Under hypoxic conditions, levels of A2aR, SDF-1, and CXCR4 were significantly increased compared to those under normoxia. The trend of SDF-1 and CXCR4 being inhibited when A2aR is up-regulated was more obvious in the baicalin intervention group. Baicalin directly enhanced A2aR expression, and A2aR knockdown weakened the function of baicalin. SDF-1 and CXCR4 expression levels were increased in the hypoxia + A2aR knockdown group, as were the proliferation and migration rates of PASMCs, while the apoptotic rate was decreased. Baicalin and CGS21680 showed opposite effects.

Conclusions

Our data indicate that baicalin efficiently attenuates hypoxia-induced PASMC proliferation, migration, and apoptotic resistance, as well as SDF-1 secretion, by up-regulating A2aR and down-regulating the SDF-1/CXCR4 axis.

     

Abstracts 2016

Background

Musculoskeletal pain is associated with comorbidity, extensive use of health services, long-term disability and reduced quality of life. The scientific literature on effects of treatment for musculoskeletal pain is inconclusive.

Purpose

The purpose of this study is to compare a multidisciplinary intervention (MI), including use of the novel Interdisciplinary Structured Interview with a Visual Educational Tool (ISIVET), with a brief intervention (BI), on effects on mental and physical symptoms, functioning ability, use of health services and coping in patients sick-listed due to musculoskeletal pain.

Method

Two hundred eighty-four adults aged 18–60, referred to a specialist clinic in physical rehabilitation, were randomized to MI or BI. Patients received a medical examination at baseline and completed a comprehensive questionnaire at baseline, 3 months and 12 months.

Results

Both groups reported improvements in mental and physical symptoms, including pain, and improved functioning ability at 3 and 12 months, but the MI group improved faster than the BI group except from reports of pain, which had a similar course. Significant interactions between group and time were found on mental symptoms (anxiety (p?<?0.05), depression (p?<?0.01), somatization (p?<?0.01)) and functioning ability (p?<?0.01) due to stronger effects in the MI group at 3 months. At 3 and 12 months, the MI group reported significantly less use of health services (general practitioner (p?<?0.05)). At 12 months, the MI group reported better self-evaluated capability of coping with complaints (p?<?0.001) and they took better care of their own health (p?<?0.001), compared to the BI group.

Conclusion

The results indicate that the MI may represent an important supplement in the treatment of musculoskeletal pain.

     

Ontological analysis of SNOMED CT

Background

SNOMED CT is the most comprehensive medical terminology. However, its use for intelligent services based on formal reasoning is questionable.

Methods

The analysis of the structure of SNOMED CT is based on the formal top-level ontology DOLCE.

Results

The analysis revealed several ontological and knowledge-engineering errors, the most important are errors in the hierarchy (mostly from an ontological point of view, but also regarding medical aspects) and the mixing of subsumption relations with other types (mostly 'part of').

Conclusion

The found errors impede formal reasoning. The paper presents a possible way to correct these problems.

     

Role of the immune system in cardiac tissue damage and repair following myocardial infarction

Introduction

The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation.

Results

At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair.

Conclusions

It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

     

A pathway to a stronger research culture in health policy

Background

There are currently limited pathways into a career in health policy research in Australia, due in part to a serious absence of health policy research capability in Australian universities.

Discussion

We define what we consider health policy research and education should comprise. We then examine what is currently on offer and propose ways to strengthen health policy research in Australia.

Summary

This paper, which is part analysis and part commentary, is offered to provoke wider debate about how health policy research can be nurtured in Australia.

     

Angiotensin 1–7, but not the thrombin-cleaved osteopontin C-terminal fragment,attenuates osteopontin-mediated macrophage-induced endothelial-cell inflammation

Objective and design

Evaluating the pro-/anti-inflammatory activity of the C-terminal cleavage product of osteopontin in comparison to angiotensin 1–7.

Material and subjects

Human coronary endothelial cells (hcEC) treated with conditioned media from human U937 macrophages.

Treatment

Macrophages were (pre)treated with C-terminal, full-length or N-terminal osteopontin (OPN-C, OPN-FL, OPN-N, respectively), angiotensin II, angiotensin 1–7 or TNF-α. OPN-C modulatory capacity was compared to that of Ang1–7 in inhibiting subsequent Ag II, OPN-FL or OPN-N-induced macrophage-mediated endothelial inflammation.

Methods

Protein expression of NFκB, IκB, vCAM-1 and iCAM-1 was assessed using western blot. Promotor activation by NFκB was also assessed by dual-luciferase reporter assay.

Results

Conditioned media of macrophages treated with OPN-C induced hcECs’ NfκB activation to a lower degree than OPN-FL or OPN-N. Priming of macrophages with angiotensin 1–7 attenuated the endothelial pro-inflammatory effect induced by subsequent exposure of the macrophages to angiotensin II, OPN-FL or OPN-N. This was evidenced by both NfκB activation and vCAM and iCAM expression. In contrast, priming macrophages with OPN-C did not significantly attenuate the subsequent response to the pro-inflammatory cytokines.

Conclusions

OPN-C induces lower macrophage-induced endothelial inflammation compared to OPN-FL or OPN-N, but unlike angiotensin 1–7, fails to prevent endothelial inflammation induced by subsequent pro-inflammatory macrophage stimulation.

     

Stressful Parental-Bonding Exaggerates the Functional and Emotional Disturbances of Primary Dysmenorrhea

Background

Some evidence suggests that women with primary dysmenorrhea (or painful period) often have traumatic experience with parental attachments, but the exact relationship is still unclear.

Purpose

This study aims to investigate associations between styles of the parental bonding and the detailed aspects of the disorder in Chinese university-student women.

Methods

From university-student women, we have invited 50 primary dysmenorrhea patients and 111 healthy volunteers, to undergo tests of the Functional and Emotional Measure of Dysmenorrhea (FEMD), the Family Relationship Questionnaire (FRQ), and the visual analogue scale for the pain intensity experienced.

Results

Besides the high scores of the FEMD Functional and Emotional scales, the dysmenorrhea patients also scored significantly higher than the healthy controls on the FRQ scales of Paternal Dominance and Maternal Abuse. In patients, the FEMD Emotional scale was negatively predicted by the Paternal Freedom Release scale, and the FEMD Functional scale was positively predicted by the Maternal Dominance scale.

Conclusions

Inappropriate parental bonding or chronic traumatic attachment styles have respective relationships with the functional and emotional disturbances experienced by the primary dysmenorrhea patients.