bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of psychosocial stimulation on the development, growth, and treatment outcome of children with severe acute malnutrition age 6–59 months in southern Ethiopia: a parallel group cluster randomized control trial (EPSoSAMC study)
Authors: Tessema Tesfalem T. , Alamdo Andamlak G. , Yirtaw Tewodrose G. , Deble Fana A. , Mekonen Eyoel B. , Abessa Teklu G. , Lema Tefera B.
Published: December 2019

Background

Severe Acute Malnutrition (SAM) remains a major cause of child mortality. To improve the management and survival of children the World Health Organization (WHO) endorsed the protocol for the management of SAM. The protocol suggested the integration of psychosocial stimulation as part of the medico-nutritional care process to prevent the long-term adverse developmental impact of the SAM. However, there is little scientific evidence behind the recommended stimulation intervention.

Method

A parallel-group cluster-randomized controlled trial will be conducted among 144 children with SAM age 6–59 months in Southern Ethiopia. The study will have two groups where: children with SAM admitted in the intervention health facilities will receive psychosocial stimulation in addition to the routine inpatient care and for 6 months after discharge. Children with SAM admitted in the SC of the control health facilities will receive the routine inpatient care without psychosocial stimulation and home-based follow up for 6 months after discharge. All mothers/ caregivers will also receive uniform health education on child health-related issues. The primary outcome of the study will be child development while the secondary outcomes will include child growth and treatment outcome. All outcomes will be assessed four times: at enrollment, upon discharge from the SC, at 3 and 6 months of follow up. The data will be analyzed using STATA Version 15 Statistical Software. The anthropometric Z-scores and percentile of the median will be calculated child using WHO Anthro Version 3.2.2 Statistical Software. To assess the overall effect of the intervention by controlling other potential contributing factors, a generalized linear mixed model will be used.

Discussion

The present study will have an important contribution in generating supplementary evidence regarding the effect of psychosocial stimulation interventions on the development and growth outcomes of children with SAM. The study will further address the impact of the intervention on treatment outcome indicators that are still under-researched areas requiring new scientific evidence.

Trial registration

Pan African Clinical Trials Registry -PACTR201901730324304. Registered 25 November 2018,https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=5739
Physical rehabilitation in the context of a landslide that occurred in Brazil
Authors: Carvalho M. L. , Freitas C. M. , Miranda E. S.
Published: December 2019

Backgrounds

The efforts to develop research and training on physical rehabilitation in regards to disasters is considered recent worldwide. In the late evening of the 11th up until the 12th of January of 2011, the most massive natural disaster occurred in Brazil with extremely heavy downpour, abrupt flood, as well as landslides on multiple areas of the Mountain Region of Rio de Janeiro. The objective of this research was to investigate the challenges in terms of physical rehabilitation provided by this event

Methods

The cross-sectional mixed method’s study, which was conducted in the city of Nova Friburgo, used two different data sources: hospital records on traumatic injuries pre and post disaster, and interviews with key informants - victims who suffered injuries related to the disaster, professionals from rehabilitation services in the municipality, and also the city’s health service management. Pearson’s chi-squared test was performed to evaluate statistical significance between the week of a given incident and the type of injury. Interviews were transcribed and analysed through content analysis.

Results

A total of 2326 hospital records and 27 interviews were analysed. The proportion of traumatic injury in the municipal emergency service increased from 16% in the prior week, to 40% in the week post-disaster (p <  0.0001). Different injuries were identified: multiple fractures, crushing, amputation, perforation of soft tissues, inhalation of dust and establishment of chronic conditions through stress. Despite this scenario, out of the 16 health professionals interviewed, twelve did not observe an increase in the demand for outpatient rehabilitation services after the disaster. Interviews with the victims revealed that the pathways for care ran into different barriers. From 11 victims interviewed, only one received complete physiotherapy care through the public health services in the city, while all others hired additional assistance, received volunteer services, had assistance in other cities or remained without rehabilitation.

Conclusions

The needs for rehabilitation increased after the disaster; however, the demand was repressed due to different barriers such as competing needs and possible lack of medical referral. Recommendations were made, including the action of performing a search of victims with rehabilitation needs.
Probing the composition of Plasmodium species contained in malaria infections in the Eastern region of Ghana
Authors: Amoah Linda Eva , Donu Dickson , Abuaku Benjamin , Ahorlu Colins , Arhinful Daniel , Afari Edwin , Malm Keziah , Koram Kwadwo Ansah
Published: December 2019

Background

Asymptomatic falciparum and non-falciparum malaria infections are major challenges to malaria control interventions, as they remain a source of continual infection in the community. This becomes even more important as the debate moves towards elimination and eradication. This study sought to quantify the burden of Plasmodium malaria infection in seven communities in the Eastern Region of Ghana.

Methods

The cross-sectional study recruited 729 participants aged 85 years old and below from 7 closely linked communities. Finger pricked blood was used to prepare thick and thin blood smears as well as spot filter paper and an histidine rich protein 2 (HRP2) rapid diagnostic test kit (RDT). Genomic DNA was extracted from the filter paper dry blood spot (DBS) and used in PCR to amplify the Plasmodium 18S rRNA gene using species specific PCR.

Results

96.6% of the participants were identified as afebrile, with axillary temperatures below 37.5 °C. PCR identified 66% of the participants to harbor malaria parasites, with 9 P. malariae and 7 P. ovale mono-infections accounting for 2.2% and P. falciparum combined with either 36 P. malariae or 25 P. ovale infections, accounting for 13.3%. Parasite prevalence by microscopy (32%) was similar to the RDT positivity rate (33%). False positive RDT results ranged from 64.6% in children aged between 5 and 9 years to 10% in adults aged 20 years and above. No significant differences were observed in falciparum and non-falciparum parasite carriage at the community level, however young adults aged between 15 and 19 years had the highest prevalence (34.8% (16/46)) of P. falciparum and P. malariae parasite carriage whilst children aged between 5 and 9 years had the highest level (11.4% (14/123)) of P. ovale carriage.

Conclusion

The high rate of misidentification of non-falciparum parasites and the total absence of detection of P. ovale by microscopy suggests that more sensitive malaria diagnostic tools including molecular assays are required to accurately determine the prevalence of carriers of non-falciparum parasites and low density P. falciparum infections, especially during national surveillance exercises. Additionally, malaria control interventions targeting the non-falciparum species P. malariae and P. ovale parasites are needed.
Back beliefs in patients with low back pain: a primary care cohort study
Authors: Grøn Søren , Jensen Rikke Krüger , Jensen Tue Secher , Kongsted Alice
Published: December 2019

Background

The Back Belief Questionnaire (BBQ) measures beliefs about negative consequences of back pain. The aim of this study was to describe the back beliefs of a large clinical population with low back pain (LBP), to investigate the associations between back beliefs and patient characteristics when care-seeking, and between on-going pain and back beliefs at follow up.

Methods

Patients aged over 18, consulting with LBP with or without radicular pain of all symptom durations, were recruited from chiropractic clinics. The BBQ was completed on the first visit and at 3- and 12-month follow-ups. Sociodemographic- and symptom-related questions were answered at baseline. A BBQ sum score was calculated at all three time points, and linear regression was used to analyse the cross-sectional association between baseline patient characteristics and BBQ scores. Wilcoxon signed-rank test was used to test differences in BBQ scores for patients with and without on-going LBP at 3- and 12-months follow up.

Results

The baseline population consisted of 2295 participants. The median BBQ sum scores at baseline, 3 and 12 months had interquartile ranges of 33 [29–36], 33 [29–37], and 31 [27–35] respectively. Patient characteristics and symptoms were associated with baseline BBQ scores (p < 0.05), but most association were weak. The strongest association was with severe disability (4.0 points (95% CI 3.3–4.6) lower BBQ than no disability). Negative beliefs were related to more severe LBP at baseline and with on-going pain at follow up.

Conclusion

At a population level, back beliefs were generally positive and relatively constant over time, but misconceptions about a poor prognosis were common. Studies exploring individual patterns of back beliefs and associations with clinical outcomes over time are recommended.
A rare case of Sweet syndrome secondary to melioidosis
Authors: Vithoosan Sahathevan , Thanushah Balendran , Piranavan Paramarajan , Gamlaksha Dayal , Karunatilake Harindra , Jayanaga Ananda
Published: December 2019

Background

Melioidosis is an emerging infection in South Asia caused by Burkholderia pseudomallei with various clinical presentations that include pneumonia, bacteraemia, arthritis, and deep-seated abscesses. Various cutaneous manifestations have been described in association with melioidosis. However Sweet Syndrome secondary to melioidosis has not been reported in the literature. Herein we describe the first case of Sweet syndrome secondary to melioidosis.

Case presentation

A 53-year-old previously healthy Sri Lankan female presented with high-grade fever, painful oral ulcers, odynophagia and multiple bilateral cervical lymphadenopathies for 1 month. She also had a loss of appetite and weight. She had oral ulcers and bilateral blepharitis. Dermatological examination revealed multiple tender papules with a mamillated appearance and targetoid lesions with a yellowish centre over the face, upper trunk and upper limbs. She also had multiple tender subcutaneous nodules over the extensor aspect of upper limbs. Her inflammatory markers were significantly elevated. Aspirate from a submental lymph node abscess revealed the growth of Burkholderia pseudomallei. Melioidosis antibody titer was > 10,240. The histology of the skin lesions of the face and left forearm showed a prominent neutrophilic infiltrate in the dermis and the morphological features were in favour of Sweet syndrome with panniculitis. She was started on intravenous meropenem 2 g daily and showed rapid clinical improvement with the disappearance of skin lesions as well as a reduction in inflammatory markers.

Conclusion

Sweet syndrome is an uncommon inflammatory disorder known to be associated with upper respiratory tract and gastrointestinal infections, malignancies and the use of certain drugs. Melioidosis is an emerging infection with various cutaneous manifestations. This is the first case of melioidosis causing the secondary sweet syndrome. It emphasizes the importance of considering melioidosis as a potential aetiology in patients with Sweet syndrome.
Immediate implant placement in anterior teeth with grafting material of autogenous tooth bone vs xenogenic bone
Authors: Wu Dong , Zhou Lin , Lin Jichao , Chen Jiang , Huang Wenxiu , Chen Yonghui
Published: December 2019

Background

The aim of the study was to compare the efficacy of the autogenous tooth bone and xenogenic bone grafted in immediate implant placement with bone defect.

Methods

Thirty patients whose compromised anterior teeth need immediate implant placement were enrolled. Autogenous tooth bone made from the extracted teeth by chair-side or the xenogenic bone were used to repaired bone defect. Clinical examination, radiographic assessment about the horizontal bone change in the level of 0 mm, 3 mm and 6 mm below the implant neck and the marginal bone loss were made immediately, 6 and 12 months after implant placement. Questionnaire of the feelings about the surgery were made at the time of removing the sutures.

Results

All implants achieved the success criteria without any complications at the follow-up period. The percent of the horizontal bone change and the marginal bone loss at 6 and 12 months were almost the same between two groups (P > .05). The horizontal bone loss at the first or the latter 6 months was almost the same (P > .05). But the horizontal bone loss at the 6 mm level was less than the 0 mm and 3 mm levels at 6 and 12 months (P < .05). Meanwhile patients seem more satisfied with the autogenous tooth bone derived from the questionnaire.

Conclusion

The bone volume change in the facial part of the implant after immediate placement is almost the same between two groups. Providing clinical evidence that the autogenous tooth bone made from compromised tooth can be an acceptable bone graft material.
Water-separated part of Chloranthus serratus alleviates lipopolysaccharide- induced RAW264.7 cell injury mainly by regulating the MAPK and Nrf2/HO-1 inflammatory pathways
Authors: Sun Shuping , Du Yunyan , Yin Chuanliu , Suo Xiaoguo , Wang Rui , Xia Rongping , Zhang Xiaoping
Published: December 2019

Background

Chloranthus serratus(Chloranthaceae) has been used to treat bruises, rheumatoid and bone pain. However, the anti-inflammatory mechanisms ofC. serratusin vitro have not been fully elucidated. The present study aimed to explore the anti-inflammatory activity and potential mechanisms ofC. serratus’s separated part of water (CSSPW) in lipopolysaccharide (LPS)-induced RAW264.7 cells.

Methods

The concentrations of CSSPW were optimized by CCK-8 method. Nitric oxide (NO) content was detected by one-step method. The levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Gene expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was detected by real-time quantitative PCR (qPCR). Immunofluorescence and DCFH-DA fluorescent probes were used to detect p65 nuclear translocation and reactive oxygen species (ROS) content, respectively. Western blotting was used to assay the protein expression of mitogen-activated protein kinases (MAPK), nuclear factor-kappa B (NF-κB) and nuclear transcription factor E2 related factor 2/haem oxygenase-1 (Nrf2/HO-1) pathways.

Results

The final concentrations of 15 ng/mL, 1.5 μg/mL and 150 μg/mL were selected as low, medium and high doses of CSSPW, respectively. CSSPW treatment significantly reduced the generation of NO, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandinE2(PGE2), iNOS mRNA and COX-2 mRNA in response to LPS stimulation. Furthermore, the protein expression of the MAPK and NF-κB pathways was suppressed by CSSPW treatment, as well as p65 nuclear translocation and ROS production. In contrast, the protein expression of the Nrf2/HO-1 pathway was markedly upregulated.

Conclusions

CSSPW exerts its anti-inflammatory effect via downregulating the production of pro-inflammatory mediators, inhibiting the activation of NF-κB and MAPK pathways, as well as activating Nrf2/HO-1 pathway in LPS-induced RAW264.7 cells.
Anti-inflammatory effects of a methanol extract of Dictamnus dasycarpus Turcz. root bark on imiquimod-induced psoriasis
Authors: Choi Minjee , Yi Jun Koo , Kim Si-Yong , Ryu Jung Hyun , Lee Jinhee , Kwon Wookbong , Jang Soyoung , Kim Dongjun , Kim MyoungOk , Kim Hyungwoo , Kim Sung Hyun , Choi Seong-Kyoon , Ryoo Zae Young
Published: December 2019

Background

The root bark of Dictamnus dasycarpus Turcz. has been successfully used for the treatment of inflammatory skin conditions such as eczema and pruritus. However, the anti-psoriatic effect of this plant has not until now been investigated.

Methods

The aim of this project was to investigate whether a methanol extract of Dictamnus dasycarpus Turcz. root bark (MEDD) can be used as a therapeutic agent for psoriasis in C57BL/6 mice model of imiquimod (IMQ)-induced psoriasis. IMQ and MEDD was applied to mouse skin continuously for 7 days. The skin phenotype and the levels of inflammatory cytokines, such as interferon (IFN)-γ and interleukin (IL)-17, were analyzed. The immune cell population was determined by flow cytometry, and STAT1 and 3 protein levels were measured.

Results

An alleviation of scaly skin phenotype, immune cell infiltration in the dermis, and epidermal hyperplasia was observed after daily MEDD treatment in the lesion-affected area. It was also found that MEDD reduced IL-17 cytokine levels decreased by 44.37% (p < 0.05), the number of IL-17-producing Th17 cells and γδT cells, and the size of the Th1 population secreting IFN-γ decreased by 45.98, 62.21, and 44.42%, respectively (p < 0.05), compared with the vehicle control group. STAT3 signals, associated with IL-17 are also reduced by MEDD.

Conclusions

An anti-psoriatic effect of MEDD was observed, as determined by decreased skin inflammation, reduced number of inflammatory cytokines, and a smaller population of inflammatory cells. These results contribute to the validation of the use of MEDD in the treatment of psoriasis.
Neighbourhood Team Development to promote resident centred approaches in nursing homes: a protocol for a multi component intervention
Authors: Boscart Veronique M. , Sidani Souraya , Ploeg Jenny , Dupuis Sherry L. , Heckman George , Kim Jessica Luh , d’Avernas Josie , Brown Paul
Published: December 2019

Background

As the demand for nursing home (NH) services increases, older adults and their families expect exceptional services. Neighbourhood Team Development (NTD) is a multi-component intervention designed to train team members (staff) in the implementation of resident-centered care in NH settings. A neighbourhood is a 32-resident home area within a NH. This paper presents the protocol used to implement and evaluate NTD. The evaluation aimed to 1) examine fidelity with which the NTD was implemented across NHs; 2) explore contextual factors associated with implementation and outcomes of the NTD; and 3) examine effects of NTD on residents, team members, family, and organizational outcomes, and the association between level of implementation fidelity and outcomes.

Methods

The study employed a repeated measure, mixed method design. NTD consisted of a 30-month standardised training and implementation plan to modify the physical environment, organize delivery and services and align staff members to promote inter-professional team collaboration and enhanced resident centeredness. Training was centred in each 32-resident neighbourhood or home area. Quantitative and qualitative data were collected with reliable and valid measures over the course of 3 years from residents (clinical outcomes, quality of life, satisfaction with care, perception of person centeredness, opportunities for social engagement), families (satisfaction with care for relative, person centeredness, relationship opportunities), team members (satisfaction with job, ability to provide person centered care, team relationships) and organizations (retention, turnover, staffing, events) in 6 NHs. Mixed models were used for the analysis.

Discussion

The advantages and limitations of the NTD intervention are described. The challenges in implementing and evaluating this multi-component intervention are discussed as related to the complexity of the NH environment.

Trial registration

ClinicalTrials.gov ID: NCT03415217 (January 30, 2018 – Retrospectively registered).
The functional roles of IGF-1 variants in the susceptibility and clinical outcomes of mild traumatic brain injury
Authors: Wang Yu-Jia , Wong Henry Sung-Ching , Wu Chung-Che , Chiang Yung-Hsiao , Chiu Wen-Ta , Chen Kai-Yun , Chang Wei-Chiao
Published: December 2019

Background

Insulin-like growth factor 1 (IGF-1) is an important pleiotropic hormone that exerts neuroprotective and neuroreparative effects after a brain injury. However, the roles of IGF-1 variants in mild traumatic brain injury (mTBI) are not yet fully understood. This study attempted to elucidate the effects of IGF-1 variants on the risk and neuropsychiatric outcomes of mTBI.

Methods

Based on 176 recruited mTBI patients and 1517 control subjects from the Taiwan Biobank project, we first compared the genotypic distributions of IGF-1 variants between the two groups. Then, we analyzed associations of IGF-1 variants with neuropsychiatric symptoms after mTBI, including anxiety, depression, dizziness, and sleep disturbances. Functional annotation of IGF-1 variants was also performed through bioinformatics databases.

Results

The minor allele of rs7136446 was over-represented in mTBI patients compared to community-based control subjects. Patients carrying minor alleles of rs7136446 and rs972936 showed more dizziness and multiple neuropsychiatric symptoms after brain injury.

Conclusions

IGF-1 variants were associated with the risk and neuropsychiatric symptoms of mTBI. The findings highlight the important role of IGF-1 in the susceptibility and clinical outcomes of mTBI.
HSV-1 triggers paracrine fibroblast growth factor response from cortical brain cells via immediate-early protein ICP0
Authors: Hensel Niko , Raker Verena , Förthmann Benjamin , Detering Nora Tula , Kubinski Sabrina , Buch Anna , Katzilieris-Petras Georgios , Spanier Julia , Gudi Viktoria , Wagenknecht Sylvia , Kopfnagel Verena , Werfel Thomas Andreas , Stangel Martin , Beineke Andreas , Kalinke Ulrich , Paludan Søren Riis , Sodeik Beate , Claus Peter
Published: December 2019

Background

Herpes simplex virus-1 (HSV-1) infections of the central nervous system (CNS) can result in HSV-1 encephalitis (HSE) which is characterized by severe brain damage and long-term disabilities. Different cell types including neurons and astrocytes become infected in the course of an HSE which leads to an activation of glial cells. Activated glial cells change their neurotrophic factor profile and modulate inflammation and repair. The superfamily of fibroblast growth factors (FGFs) is one of the largest family of neurotrophic factors comprising 22 ligands. FGFs induce pro-survival signaling in neurons and an anti-inflammatory answer in glial cells thereby providing a coordinated tissue response which favors repair over inflammation. Here, we hypothesize that FGF expression is altered in HSV-1-infected CNS cells.

Method

We employed primary murine cortical cultures comprising a mixed cell population of astrocytes, neurons, microglia, and oligodendrocytes. Astrocyte reactivity was morphometrically monitored by an automated image analysis algorithm as well as by analyses of A1/A2 marker expression. Altered FGF expression was detected by quantitative real-time PCR and its paracrine FGF activity. In addition, HSV-1 mutants were employed to characterize viral factors important for FGF responses of infected host cells.

Results

Astrocytes in HSV-1-infected cortical cultures were transiently activated and became hypertrophic and expressed both A1- and A2-markers. Consistently, a number of FGFs were transiently upregulated inducing paracrine neurotrophic signaling in neighboring cells. Most prominently, FGF-4, FGF-8, FGF-9, and FGF-15 became upregulated in a switch-on like mechanism. This effect was specific for CNS cells and for a fully functional HSV-1. Moreover, the viral protein ICP0 critically mediated the FGF switch-on mechanism.

Conclusions

HSV-1 uses the viral protein ICP0 for the induction of FGF-expression in CNS cells. Thus, we propose that HSV-1 triggers FGF activity in the CNS for a modulation of tissue response upon infection.
Evaluation of a new software prototype for frameless radiosurgery of arteriovenous malformations
Authors: Schmidhalter Daniel , Henzen Dominik , Herrmann Evelyn , Volken Werner , Mackeprang Paul-Henry , Ermis Ekin , Hemmatazad Hossein , Honegger Jonas , Haas Benjamin , Fix Michael K. , Manser Peter
Published: December 2019

Background

In order to locate an arteriovenous malformation, typically, a digital subtraction angiography (DSA) is carried out. To use the DSA for target definition an accurate image registration between CT and DSA is required. Carrying out a non-invasive, frameless procedure, registration of the 2D-DSA images with the CT is critical. A new software prototype is enabling this frameless procedure. The aim of this work was to evaluate the prototype in terms of targeting accuracy and reliability based on phantom measurements as well as with the aid of patient data. In addition, the user’s ability to recognize registration mismatches and quality was assessed.

Methods

Targeting accuracy was measured with a simple cubic, as well as with an anthropomorphic head phantom. Clearly defined academic targets within the phantoms were contoured on the CT. These reference structures were compared with the structures generated within the prototype. A similar approach was used with patient data, where the clinically contoured target served as the reference structure.

An important error source decreasing the target accuracy comes from registration errors between CT and 2D-DSA. For that reason, the tools in BC provided to the user to check these registrations are very important. In order to check if the user is able to recognize registration errors, a set of different registration errors was introduced to the correctly registered CT and 2D-DSA image data sets of three different patients. Each of six different users rated the whole set of registrations within the prototype.

Results

The target accuracy of the prototype was found to be below 0.04 cm for the cubic phantom and below 0.05 cm for the anthropomorphic head phantom. The mean target accuracy for the 15 patient cases was found to be below 0.3 cm.

In the registration verification part, almost all introduced registration errors above 1° or 0.1 cm were detected by the six users. Nevertheless, in order to quantify and categorize the possibility to detect mismatches in the registration process more data needs to be evaluated.

Conclusion

Our study shows, that the prototype is a useful tool that has the potential to fill the gap towards a frameless procedure when treating AVMs with the aid of 2D-DSA images in radiosurgery. The target accuracy of the prototype is similar to other systems already established in clinical routine.
Organotypic brain slice cultures to model neurodegenerative proteinopathies
Authors: Croft C. L. , Futch H. S. , Moore B. D. , Golde T. E.
Published: December 2019

Organotypic slice cultures of brain or spinal cord have been a longstanding tool in neuroscience research but their utility for understanding Alzheimer’s disease (AD) and other neurodegenerative proteinopathies has only recently begun to be evaluated. Organotypic brain slice cultures (BSCs) represent a physiologically relevant three-dimensional model of the brain. BSCs support all the central nervous system (CNS) cell types and can be produced from brain areas involved in neurodegenerative disease. BSCs can be used to better understand the induction and significance of proteinopathies underlying the development and progression of AD and other neurodegenerative disorders, and in the future may serve as bridging technologies between cell culture and in vivo experiments for the development and evaluation of novel therapeutic targets and strategies. We review the initial development and general use of BSCs in neuroscience research and highlight the advantages of these cultures as an ex vivo model. Subsequently we focus on i) BSC-based modeling of AD and other neurodegenerative proteinopathies ii) use of BSCs to understand mechanisms underlying these diseases and iii) how BSCs can serve as tools to screen for suitable therapeutics prior to in vivo investigations. Finally, we will examine i) open questions regarding the use of such cultures and ii) how emerging technologies such as recombinant adeno-associated viruses (rAAV) may be combined with these models to advance translational research relevant to neurodegenerative disorders.
Changes in circulating microRNA after recumbent isometric yoga practice by patients with myalgic encephalomyelitis/chronic fatigue syndrome: an explorative pilot study
Authors: Takakura Shu , Oka Takakazu , Sudo Nobuyuki
Published: December 2019

Background

Yoga is a representative mind-body therapy. Our previous studies have demonstrated that isometric yoga (i.e. yoga programs that we developed so individuals can practice yoga poses with a self-adjustable isometric load) reduces the fatigue of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, the underlying mechanisms remain unclear. Several studies have suggested that the micro-ribonucleic acid (miRNA) expression of ME/CFS patients is different from that of healthy subjects. However, it has not to date been determined if the practice of isometric yoga can affect miRNA expression. Therefore, we sought to investigate if isometric yoga is associated with changes in the expression levels of serum miRNA of patients with ME/CFS.

Methods

The study included nine patients with ME/CFS who failed to show satisfactory improvement after at least 6 months of treatment administered at our hospital. Patients practiced recumbent isometric yoga for 3 months; they met with a yoga instructor every 2 to 4 weeks and participated in daily in-home sessions. The effect of recumbent isometric yoga on fatigue was assessed by comparing pre- and post-intervention scores on the Japanese version of the 11-item Chalder fatigue scale (CFQ 11). Patient blood samples were drawn pre- and post-intervention, just prior to practicing recumbent isometric yoga with an instructor. The serum was used for miRNA array analysis with known human miRNAs.

Results

The average CFQ 11 score decreased significantly (from 25.3 ± 5.5 to 17.0 ± 5.8, p <  0.0001) after practicing recumbent isometric yoga for 3 months. The miRNA microarray analysis revealed that four miRNAs were significantly upregulated, and 42 were downregulated after the intervention period.

Conclusions

This explorative pilot study is the first to demonstrate changes in the serum levels of several miRNAs after regular practice of recumbent isometric yoga. These miRNAs might represent biomarkers for the fatigue-relieving effects of isometric yoga of patients with ME/CFS.

Trial registration

University Hospital Medical Information Network (UMIN CTR) 000023472. Registered Aug 4, 2016.
An evaluation of the teen and Youth Mental Health First Aid training with a CALD focus: an uncontrolled pilot study with adolescents and adults in Australia
Authors: Uribe Guajardo Maria Gabriela , Kelly Claire , Bond Kathy , Thomson Russell , Slewa-Younan Shameran
Published: December 2019

Background

Australia is an ethnically diverse nation with one of the largest refugee resettlement programs worldwide. Evidence suggests that although the risk of developing mental disorders in culturally linguistically diverse (CALD) adolescents may be elevated, professional help-seeking in CALD youth is low. This study sought to evaluate the face-to-face teen (tMHFA) and Youth Mental Health First Aid (YMHFA) training with a CALD focus, which aimed at improving mental health literacy (MHL) and skills in youth and adults assisting adolescents with mental health problems.

Methods

An uncontrolled pre-, post-, and follow-up design was used to measure improvement in MHL measures in year 10 students and adults.

Results

A total of 372 year 10 students from 2 high schools were trained. 308 responded to the pre-training questionnaire, 220 responded to the post-training questionnaire, and 256 completed the 3-month follow-up questionnaire. A total of 34 adults were trained, 32 responded to the pre-questionnaire and 31 responded to the post-training questionnaire and 20 completed the 3-month follow-up questionnaire. Following training, students were more likely to endorse ‘helpful’ adults as valid sources of help (p < 0.001) and these gains were maintained at follow-up (p < 0.01). Significantly higher levels of concordant (helpful) helping intentions were found after training (p < 0.01), and this was maintained at follow-up (p < 0.05). Significant lower levels of discordant (harmful) helping intentions were found after training (p < 0.001), and this was maintained at follow-up (p < 0.01). A significant improvement in adults’ knowledge of youth mental health problems and Youth Mental Health First Aid was noted from pre- to post-training (p < 0.01) and was maintained at follow-up (p < 0.01). Confidence when helping a young person with mental health problems increased significantly after training (p < 0.001) and this was maintained at follow-up (p < 0.05).

Conclusion

Our findings indicated the training led to an improvement in a number of measures of MHL and helpful intentions of both the adolescents and adults evaluated. These results indicate that CALD tMHFA and YMHFA are a recommended way of upskilling those trained and thereby leading to the improvement youth mental health in areas with high proportion of ethnically diverse groups.
Sample size re-estimation in crossover trials: application to the AIM HY-INFORM study
Authors: Wych Julie , Grayling Michael J. , Mander Adrian P.
Published: December 2019

Background

Crossover designs are commonly utilised in randomised controlled trials investigating treatments for long-term chronic illnesses. One problem with this design is its inherent repeated measures necessitate the availability of an estimate of the within-person standard deviation (SD) to perform a sample size calculation, which may be rarely available at the design stage of a trial. Interim sample size re-estimation designs can be used to help alleviate this issue by adapting the sample size mid-way through the trial, using accrued information in a statistically robust way.

Methods

The AIM HY-INFORM study is part of the Informative Markers in Hypertension (AIM HY) Programme and comprises two crossover trials, each with a planned recruitment of 600 participants. The objective of the study is to test whether blood pressure response to first line antihypertensive treatment depends on ethnicity. An interim analysis is planned to reassess the assumptions of the planned sample size for the study. The aims of this paper are: (1) to provide a formula for sample size re-estimation in both crossover trials; and (2) to present a simulation study of the planned interim analysis to investigate alternative within-person SDs to that assumed.

Results

The AIM HY-INFORM protocol sample size calculation fixes the within-person SD to be 8 mmHg, giving > 90% power for a primary treatment effect of 4 mmHg. Using the method developed here and simulating the interim sample size reassessment, if we were to see a larger within-person SD of 9 mmHg at interim, 640 participants for 90% power 90% of the time in the three-period three-treatment design would be required. Similarly, in the four-period four-treatment crossover design, 602 participants would be required.

Conclusions

The formulas presented here provide a method for re-estimating the sample size in crossover trials. In the context of the AIM HY-INFORM study, simulating the interim analysis allows us to explore the results of a possible increase in the within-person SD from that assumed. Simulations show that without increasing the planned sample size of 600 participants, we can reasonably still expect to achieve 80% power with a small increase in the within-person SD from that assumed.

Trial registration

ClinicalTrials.gov, NCT02847338. Registered on 28 July 2016.
eHealth-supported case management for patients with panic disorder or depression in primary care: Study protocol for a cRCT (PREMA)
Authors:   for the PREMA-study group, Lukaschek Karoline , Mergenthal Karola , Heider Dirk , Hanke Alexander , Munski Kathrein , Moschner Anne , Emig Michelle , van den Akker Marjan , Zapf Antonia , Wegscheider Karl , König Hans-Helmut , Gensichen Jochen
Published: December 2019

Background

Panic disorder (PD), frequently occurring with agoraphobia (AG), and depression are common mental disorders in primary care and associated with considerable individual and societal costs. Early detection and effective treatment of depression and PD/AG are of major importance. Cognitive behavioural exposure exercises have been shown to be effective in reducing anxiety and depressive symptoms. Practice team-based case management can improve clinical outcomes for patients with chronic diseases in primary care. The present study aims at evaluating the effects and cost-effectiveness of a primary care team-based intervention using behavioural therapy elements and case management supported by eHealth components in patients with PD/AG or depression compared to treatment as usual.

Methods/design

This is a two-arm cluster-randomized, controlled trial (cRCT). General practices represent the units of randomisation. General practitioners recruit adult patients with depression and PD ± AG according to the International Classification of Diseases, version 10 (ICD-10). In the intervention group, patients receive cognitive behaviour therapy-oriented psychoeducation and instructions to self-managed exposure exercises in four manual-based appointments with the general practitioner. A trained health care assistant from the practice team delivers case management and is continuously monitoring symptoms and treatment progress in ten protocol-based telephone contacts with patients. Practice teams and patients are supported by eHealth components. In the control group, patients receive usual care from general practitioners. Outcomes are measured at baseline (T0), at follow-up after 6 months (T1), and at follow-up after 12 months (T2). The primary outcome is the mental health status of patients as measured by the Mental Health Index (MHI-5). Effect sizes of 0.2 standard deviation (SD) are regarded as relevant. Assuming a drop-out rate of 20% of practices and patients each, we aim at recruiting 1844 patients in 148 primary care practices. This corresponds to 12.5 patients on average per primary care practice. Secondary outcomes include depression and anxiety-related clinical parameters and health-economic costs.

Discussion

If the intervention is more effective than treatment as usual, the three-component (cognitive behaviour therapy, case-management, eHealth) primary care-based intervention for patients suffering from PD/AG or depression could be a valuable low-threshold option that benefits patients and primary care practice teams.

Trial registration

German clinical trials register, DRKS00016622. Registered on February 22nd, 2019.
Individualised behaviour change strategies for physical activity in multiple sclerosis (IPAC-MS): protocol for a randomised controlled trial
Authors: Goulding Farren L. , Evans Charity D. , Knox Katherine B. , Lim Hyun J. , Levin Michael C. , Donkers Sarah J.
Published: December 2019

Background

Multiple sclerosis (MS) is a chronic, degenerative disease of the central nervous system. Because of the long-term and unpredictable nature of the disease, the burden of MS is significant from both a patient and societal perspective. Despite a recent influx of disease-modifying therapies to treat MS, many individuals continue to experience disability that negatively affects productivity and quality of life. Previous research indicates that physical activity has a positive impact on walking function in individuals with MS, in addition to the usual beneficial effects on overall health. However, most people with MS are not active enough to gain these benefits, and a lack of support to initiate and maintain physical activity has been identified as a major barrier. This study will evaluate the impact of a novel intervention involving individualised behaviour change strategies delivered by neurophysiotherapists on increasing physical activity levels in individuals with MS who are currently inactive.

Methods/design

This single-blind, parallel-group, randomised controlled trial will be conducted in Saskatchewan, Canada. Eligible participants include individuals with MS who are ambulatory but identified as currently inactive by the self-reported Godin Leisure-Time Exercise Questionnaire (GLTEQ). The intervention will be delivered by neurophysiotherapists and includes individualised behaviour change strategies aimed at increasing physical activity over a 12-month period. The control group will receive usual care during the 12-month study period. The primary outcome is the change in physical activity level, as measured by the change in the GLTEQ score from baseline to 12 months. Secondary outcomes include the change in patient-reported outcome measures assessing MS-specific symptoms, confidence and quality of life.

Discussion

Physical activity has been identified as a top research priority by the MS community. Findings from this novel study may result in new knowledge that could significantly impact the management and overall health of individuals with MS.

Trial registration

ClinicalTrials.gov, NCT04027114. Registered on 10 July 2019.
Zinc supplementation improves body weight management, inflammatory biomarkers and insulin resistance in individuals with obesity: a randomized, placebo-controlled, double-blind trial
Authors: Khorsandi Hoda , Nikpayam Omid , Yousefi Reyhaneh , Parandoosh Maryam , Hosseinzadeh Nima , Saidpour Atoosa , Ghorbani Arman
Published: December 2019

Background

The present study was designed to determine whether zinc supplementation would increase the effects of restricted calorie diet (RCD) on obesity.

Methods and materials

A randomized, double-blind clinical trial was performed on 40 obese subjects who were randomly assigned to receive zinc supplements (30 mg/day) or placebo for a period of 15-weeks. Both groups were under a restricted calorie diet (~ 300 kcal lower than the estimated energy requirement). Anthropometric measurements, biochemical markers, appetite, and dietary intakes were determined during the study period.

Results

The reductions of body weight, body mass index, waist circumference, and hip circumference were significantly higher in the zinc group compared to the placebo group (P = 0.032, 0.025, 0.003, and 0.0001, respectively). Lower levels of high sensitivity C-reactive protein, apelin, homeostatic model assessment of insulin resistance (HOMA-IR), and appetite score were observed in the zinc group in comparison with the placebo group (P = 0.0001, 0.001, 0.031 and 0.001 respectively).

Conclusion

This study indicates that Zn supplementation with a restricted calorie diet has favorable effects in reducing anthropometric measurements, inflammatory markers, insulin resistance and appetite in individuals with obesity, and may play an effective role in the treatment of obesity.

Trial registration This clinical trial was registered at clinicaltrials.gov at the U.S. National Library of Medicine (NCT02516475).
Reducing effect of insulin resistance on alpha-synuclein gene expression in skeletal muscle
Authors: Khoshi Amirhosein , Goodarzi Golnaz , Mohammadi Rezvan , Arezumand Roghaye , Moghbeli Meysam , Najariyan Mahnaz
Published: December 2019

Background

Alpha-synuclein (SNCA) as the presynaptic protein is expressed in different tissues and prevents insulin-resistance (IR) through increasing glucose-uptake by adipocytes and muscles. However, the effect of insulin metabolism on SNCA expression has scarcely elucidated. In present study we assessed the probable effect of insulin resistance on SNCA expression in muscle C2C12 cells and also skeletal muscle tissues of type 2 diabetic mice.

Materials and methods

Sixteen male C57BL/6 mice were divided into two experimental groups, including control and type 2 diabetic mice with IR (induced by high-fat diet + low-dose streptozotocin). The animals of the study involved the measurements of fasting blood glucose, oral-glucose-tolerance-test, as well as fasting plasma insulin. Moreover, insulin-resistant and insulin-sensitive muscle C2C12 cells were prepared. The insulin-resistance was confirmed by the glucose-uptake assay. Comparative quantitative real time PCR was used to assess theSNCAexpression.

Results

The obtained results have showed a significant ~ 27% decrease inSNCAexpression level in muscle tissue of diabetic mice (P = 0.022). Moreover, there was a significant change ofSNCAexpression in insulin-resistant C2C12 cells (P < 0.001).

Conclusion

Type 2 diabetes due to insulin-resistance can decreaseSNCAgene expression in muscles. In addition to the role of SNCA in cell susceptibility to insulin and glucose uptake, the SNCA expression can also be affected by insulin metabolism.
Pituitary abscess: two case reports
Authors: Nordjoe Yaotse Elikplim , Aubin Igombe Suzanne Rita , Laamrani Fatima Zahra , Jroundi Laila
Published: November 2019

Background

Pituitary abscess is a rare condition with nonspecific symptoms that can be delayed. Proper diagnosis needs to occur preoperatively so that the management can be set up accordingly. Accurate diagnosis is challenging because many differential diagnoses can exhibit the same magnetic resonance imaging features.

Case presentation

We report two cases of pituitary abscess. The first patient was a 66-year-old Arab woman who underwent a surgical procedure for a pituitary macroadenoma and presented 3 months later with chronic headaches and panhypopituitarism. A pituitary abscess was found on the follow-up magnetic resonance imaging. The second patient was a 64-year-old Arab man with no medical history who presented with a chiasmal syndrome with headaches and panhypopituitarism. Brain magnetic resonance imaging showed a heterogeneous pituitary mass that turned out to be a pituitary abscess intraoperatively. These two patients were treated with hormone substitution, endoscopic transsphenoidal drainage, and antibiotherapy, with excellent outcomes.

Conclusions

Pituitary abscess is a rare and serious condition. Preoperative diagnosis can be challenging because of the many existing differential diagnoses upon imaging. Magnetic resonance imaging is the mainstay technique of imaging due to its multimodal nature. These cases demonstrate the variable patterns of a pituitary abscess seen on magnetic resonance imaging and the potential difficulties in achieving an accurate diagnosis preoperatively due to many other conditions potentially exhibiting the same magnetic resonance imaging features.
Priming primary care providers to engage in evidence-based discussions about cannabis with patients
Authors: Kansagara Devan , Becker William C. , Ayers Chelsea , Tetrault Jeanette M.
Published: December 2019

Cannabis use has become increasingly common in the U.S. in recent years, with legalization for medical and recreational purposes expanding to more states. With this increase in use and access, providers should be prepared to have more conversations with patients about use. This review provides an overview of cannabis terminology, pharmacology, benefits, harms, and risk mitigation strategies to help providers engage in these discussions with their patients. Current evidence for the medical use of cannabis, cannabis-related diagnoses including cannabis use disorder (CUD) and withdrawal syndromes, and the co-use of opioids and cannabis are discussed. It is crucial that providers have the tools and information they need to deliver consistent, evidence-based assessment, treatment, prevention and harm-reduction, and we offer practical guidance in these areas.