bluuebunny/crossref_metadata_2025 huggingface dataset:
A1 reactive astrocytes and a loss of TREM2 are associated with an early stage of pathology in a mouse model of cerebral amyloid angiopathy
Authors: Taylor Xavier , Cisternas Pablo , You Yanwen , You Yingjian , Xiang Shunian , Marambio Yamil , Zhang Jie , Vidal Ruben , Lasagna-Reeves Cristian A.
Published: July 2020

Background

Cerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. The mechanisms underlying the contribution of CAA to neurodegeneration are not currently understood. Although CAA is highly associated with the accumulation of amyloid beta (Aβ), other amyloids are known to associate with the vasculature. Alzheimer’s disease (AD) is characterized by parenchymal Aβ deposition, intracellular accumulation of tau, and significant neuroinflammation. CAA increases with age and is present in 85–95% of individuals with AD. A substantial amount of research has focused on understanding the connection between parenchymal amyloid and glial activation and neuroinflammation, while associations between vascular amyloid pathology and glial reactivity remain understudied.

Methods

Here, we dissect the glial and immune responses associated with early-stage CAA with histological, biochemical, and gene expression analyses in a mouse model of familial Danish dementia (FDD), a neurodegenerative disease characterized by the vascular accumulation of Danish amyloid (ADan). Findings observed in this CAA mouse model were complemented with primary culture assays.

Results

We demonstrate that early-stage CAA is associated with dysregulation in immune response networks and lipid processing, severe astrogliosis with an A1 astrocytic phenotype, and decreased levels of TREM2 with no reactive microgliosis. Our results also indicate how cholesterol accumulation and ApoE are associated with vascular amyloid deposits at the early stages of pathology. We also demonstrate A1 astrocytic mediation of TREM2 and microglia homeostasis.

Conclusion

The initial glial response associated with early-stage CAA is characterized by the upregulation of A1 astrocytes without significant microglial reactivity. Gene expression analysis revealed that several AD risk factors involved in immune response and lipid processing may also play a preponderant role in CAA. This study contributes to the increasing evidence that brain cholesterol metabolism, ApoE, and TREM2 signaling are major players in the pathogenesis of AD-related dementias, including CAA. Understanding the basis for possible differential effects of glial response, ApoE, and TREM2 signaling on parenchymal plaques versus vascular amyloid deposits provides important insight for developing future therapeutic interventions.
Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies
Authors: Dijkhoff Irini M. , Drasler Barbara , Karakocak Bedia Begum , Petri-Fink Alke , Valacchi Giuseppe , Eeman Marc , Rothen-Rutishauser Barbara
Published: July 2020

Background

Air pollution is killing close to 5 million people a year, and harming billions more. Air pollution levels remain extremely high in many parts of the world, and air pollution-associated premature deaths have been reported for urbanized areas, particularly linked to the presence of airborne nano-sized and ultrafine particles.

Main text

To date, most of the research studies did focus on the adverse effects of air pollution on the human cardiovascular and respiratory systems. Although the skin is in direct contact with air pollutants, their damaging effects on the skin are still under investigation. Epidemiological data suggested a correlation between exposure to air pollutants and aggravation of symptoms of chronic immunological skin diseases. In this study, a systematic literature review was conducted to understand the current knowledge on the effects of airborne particulate matter on human skin. It aims at providing a deeper understanding of the interactions between air pollutants and skin to further assess their potential risks for human health.

Conclusion

Particulate matter was shown to induce a skin barrier dysfunction and provoke the formation of reactive oxygen species through direct and indirect mechanisms, leading to oxidative stress and induced activation of the inflammatory cascade in human skin. Moreover, a positive correlation was reported between extrinsic aging and atopic eczema relative risk with increasing particulate matter exposure.
Incorporating operational research in programmes funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria in four sub-Saharan African countries
Authors: Camacho Salvador , Maher Dermot , Kamau Edward Mberu , Saric Jasmina , Segura Luis , Zachariah Rony , Wyss Kaspar
Published: July 2020

Background

The current study builds upon a previous situation analysis of the extent to which grants from the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) are being utilized to support operational research and implementation research (OR/IR) activities in recipient countries. The objective of this follow-up study was to identify approaches and pathways to implement an OR component into grants to the Global Fund, in four sub-Saharan African countries. Special focus was given to the Structured Operational Research and Training IniTiative (SORT IT).

Methods

The conceptual framework was based on an analysis to identify elements supporting and blocking the integration of OR, called force field analysis, and a behavioural change assessment covering aspects such as opportunity, motivation, capability and triggers to do the integration. Data were collected through online surveys and stakeholder interviews both via telephone/online conference tools and in person in four countries with a high burden of malaria and tuberculosis. These countries were Ghana, Sierra Leone, the United Republic of Tanzania and Zimbabwe. The stakeholders included programme managers, implementation partners, representatives from international organisations, academic and governmental research institutions and other individuals involved in the countries’ needs assessment and National Strategic Plan development.

Results

We identified opportunities to integrate OR into the countries’ programmes during the funding process, the country’s needs assessment being the most important one, including the need of OR-related capacity. Both the force field analysis and the behavioural change assessment showed that the necessary elements to integrate OR were present in the countries. Motivation, capability and efficiency were found to be a managerial value omnipresent across stakeholders. However, those elements were influenced by the tendency to favour tangible assets over any abstract ones, such as increasing organisational capacity in OR.

Conclusions

In each of the countries assessed, there is potential to integrating OR into the programmes supported by the Global Fund. However, given the relative lack of OR-related capacity and skills encountered, a capacity strengthening tool, such as SORT IT, would be of benefit helping to identify and carry forward OR activities sustainably.
Fibro-adipose vascular anomaly (FAVA): three case reports with an emphasis on the mammalian target of rapamycin (mTOR) pathway
Authors: Hori Yumiko , Hirose Katsutoshi , Aramaki-Hattori Noriko , Suzuki Sachi , Nakayama Robert , Inoue Masanori , Matsui Takahiro , Kohara Masaharu , Toyosawa Satoru , Morii Eiichi
Published: July 2020

Background

Fibro-adipose vascular anomaly (FAVA) is a new entity of vascular anomalies with somatic and mosaic gain-of-function mutations of the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). PIK3CA mutation excessively activates mammalian target of rapamycin (mTOR) pathway, which promotes angiogenesis and lymphangiogenesis. Histologically, FAVA is composed of intramuscular fibrous and adipose tissues with venous malformation (VM). Although sirolimus known as a mTOR inhibitor has good response to FAVA, expression pattern of the mTOR pathway was still unclear. Herein, we immunohistochemically investigated three novel FAVA patients with an emphasis on the mTOR pathway (p-S6K1, p-4EBP1 and p-AKT).

Case presentation

Case 1: A 10-year-old female had complained of pain in the left thigh since she was 6-year-old. Under the clinical diagnosis of VM, she underwent surgical resection for the lesion. Case 2: A 29-year-old female patient had complained of discomfort and mild pain in the left shoulder since she was 18-year-old. After childbirth, she had severe ongoing pain and contracture of the shoulder. Under clinical diagnosis of VM, surgical resection was performed. Case 3: A 53-year-old female had complained of pain and knee restriction after surgical treatment of a knee tumor at the age of 31. Under the clinical diagnosis of atypical lipomatous tumor or high grade liposarcoma, surgical resection was performed. Histologically, all three patients presented with characteristic features of fibrous and adipose tissues with abnormal vessels within the skeletal muscle, leading to diagnosis of FAVA. Although VM has been reported as an important finding in FAVA, immunohistological findings demonstrated that abnormal vessels comprised complex of VM and lymphatic malformation (LM) in all cases. Furthermore, besides vascular malformation, abnormal fibrous and adipose tissues of FAVA expressed mTOR pathway components.

Conclusions

We presented three new cases of FAVA. Histological and immunohistochemical analyses revealed that VM and LM complex was an important finding in FAVA, and that the mTOR pathway components were expressed in abnormal fibrous tissue, adipose tissue and vascular malformation. These findings suggested that FAVA might be a mesenchymal malformation caused by PI3K/AKT/mTOR pathway.
Mistakes from the HIV pandemic should inform the COVID-19 response for maternal and newborn care
Authors: Gribble Karleen , Mathisen Roger , Ververs Mija-tesse , Coutsoudis Anna
Published: July 2020

Background

In an effort to prevent infants being infected with SARS-CoV-2, some governments, professional organisations, and health facilities are instituting policies that isolate newborns from their mothers and otherwise prevent or impede breastfeeding.

Weighing of risks is necessary in policy development

Such policies are risky as was shown in the early response to the HIV pandemic where efforts to prevent mother to child transmission by replacing breastfeeding with infant formula feeding ultimately resulted in more infant deaths. In the COVID-19 pandemic, the risk of maternal SARS-CoV-2 transmission needs to be weighed against the protection skin-to-skin contact, maternal proximity, and breastfeeding affords infants.

Conclusion

Policy makers and practitioners need to learn from the mistakes of the HIV pandemic and not undermine breastfeeding in the COVID-19 pandemic. It is clear that in order to maximise infant health and wellbeing, COVID-19 policies should support skin-to-skin contact, maternal proximity, and breastfeeding.
Effects of type 1 diabetes mellitus on lumbar disc degeneration: a retrospective study of 118 patients
Authors: Chen Rui , Liang Xinjie , Huang Tianji , Zhong Weiyang , Luo Xiaoji
Published: July 2020

Background

The study aimed to investigate the correlation between type 1 diabetes (T1D) and lumbar disc degeneration (LDD).

Methods

A retrospective analysis of 118 patients with T1D recruited from January 2014 to March 2019 was performed, and multivariate logistic regression was used to analyse the incidence of T1D; the age, sex, and body mass index (BMI) of the patients; the disease duration and the glycosylated haemoglobin and venous blood glucose levels. All patients who suffered low back pain were assessed by MRI using the Pfirrmann grading system.

Results

A total of 118 patients with an average age of 36.99 ± 17.01 (8–85 years) were reviewed. The mean hospitalization duration, venous glucose fluctuation range, glycated haemoglobin level, highest venous glucose level, venous glucose level, and disease course duration were 13.98 ± 10.16 days, 14.99 ± 5.87 mmol/L, 9.85 ± 2.52 mmol/L, 25.29 ± 7.92 mmol/L, 13.03 ± 5.75 mmol/L and 7.30 ± 8.41 years. The average Pfirrmann scores of the different discs were 2.20 ± 0.62 (L1–2), 2.35 ± 0.67 (L2–3), 2.90 ± 0.45 (L3–4), 4.20 ± 0.52 (L4–5) and 4.10 ± 0.72 (L5–S1). The patients with T1D showed severe disc degeneration. The male sex, glycosylated haemoglobin, venous glucose and venous glucose fluctuations were significantly associated with LDD (P < 0.05).

Conclusions

Glycosylated haemoglobin, the male, venous glucose and the venous glucose fluctuation range were risk factors for LDD.
Robot-assisted orthopedic surgery in the treatment of adult degenerative scoliosis: a preliminary clinical report
Authors: Chen Xiuyuan , Feng Fan , Yu Xiaosheng , Wang Shurong , Tu Zhipeng , Han Yingchao , Li Quan , Chen Hao , Chen Zhi , Lao Lifeng , Shen Hongxing
Published: July 2020

Study design

A single-institution, retrospective cohort study.

Objective

To compare the accuracy and short-term clinical outcomes of pedicle screw placement between robot-assisted (RA) and freehand (FH) technique in the treatment of adult degenerative scoliosis (ADS).

Methods

From February 2018 to October 2019, 97 adult patients with degenerative scoliosis admitted to our department were retrospectively reviewed. Thirty-one patients received robot-assisted pedicle screw placement (RA group), and 66 patients underwent freehand pedicle screw placement (FH group). Patient demographics and short-term clinical outcomes were recorded and compared between two groups. Gertzbein-Robbins grading system was adopted to evaluate the accuracy of pedicle screw placement by means of postoperative CT scan. Short-term clinical outcomes consist of operative time, intraoperative blood loss, length of hospital stay (LOS), radiological parameters, Scoliosis Research Society-22 (SRS-22) scores before the operation, 6 months after operation, adverse events, and revisions.

Results

The accuracy of screw placement was higher than that of the FH group (clinically acceptable 98.7% vs. 92.2%; P< 0.001). Intraoperative blood loss of the RA group was less than those in the FH group (499 vs. 573 ml; P < 0.001). Operative time (283.1 vs. 291.9 min; P = 0.31) and length of stay (12.8 vs. 13.7 days; P = 0.36) were compared between RA and FH groups. In terms of radiological parameters, both of groups were improved postoperatively. The SRS-22 scores at 6 months after operation from both groups were better than those before operation. For surgery-related complication, one case had pressure sores in the RA group while two cases developed dural tears in the FH group. No revision was required in both groups.

Conclusion

Combined with other surgical correction modalities, robot-assisted pedicle screw fixation is an effective and safe method of treating degenerative scoliosis. Due to its satisfactory surgical outcomes such as higher accuracy and less trauma, it provides a good alternative for clinical practice.

Level of evidence

3.
Cardiac myxoma misdiagnosed as infective endocarditis: a case of Carney complex
Authors: Kim Chang Hun , Je Hyung Gon , Ju Min Ho , Lee Chee-Hoon
Published: July 2020

Background

Infective endocarditis and cardiac myxoma have common features including fever, systemic embolism and intra-cardiac masses. For this reason, these diseases are often misdiagnosed one for another despite proper imaging studies. Herein, we report a case of suspected infective endocarditis in a patient with acute stroke, fever and a mass adjacent to the mitral valve.

Case presentation

A 24-year-old male patient presented with recurrent fever and stroke. In view of a history of Cushing syndrome and a mobile mass in the left atrium, infective endocarditis was highly suspected. He was transferred for emergency cardiac surgical intervention. During surgery, intraoperative transesophageal echocardiography revealed a 7 cm mass attached to the interatrial septum. The mass was excised through right mini-thoracotomy and pathological examination confirmed the presence of a myxoma. Based on the above clinical findings and genetic analysis, the diagnosis of Carney complex was confirmed.

Conclusions

Infective endocarditis and cardiac myxoma have common features and can be misdiagnosed. If a young patient presenting with embolic stroke had a history of an endocrine neoplasm, Carney complex should be considered in the differential diagnosis of infective endocarditis.
Herb–drug interactions between the medicinal mushrooms Lingzhi and Yunzhi and cytotoxic anticancer drugs: a systematic review
Authors: Lam Chun Sing , Cheng Lok Pui , Zhou Li Min , Cheung Yin Ting , Zuo Zhong
Published: July 2020

Background

Lingzhi and Yunzhi are medicinal mushrooms commonly used with cytotoxic chemotherapy in cancer patients in Asian countries. The current systematic review aims to identify potential pharmacokinetic or pharmacodynamic interactions from the existing literature to ensure their effective and safe combination usage in cancer patients.

Methods

A systematic search was conducted on nine major Chinese and English databases, including China Journal Net, Allied and Complementary Medicine Database, and Ovid MEDLINE®, etc., to identify clinical, animal, and in-vitro studies that evaluate the effect of combined use of Lingzhi or Yunzhi with cytotoxic drugs. The Jadad scale was used to assess the quality of clinical studies.

Results

This search identified 213 studies, including 77 clinical studies that reported on the combined use of cytotoxic drugs with Yunzhi (n = 56) or Lingzhi (n = 21). Majority of these clinical studies demonstrated modest methodological quality. In clinical practice, the most commonly used cytotoxic drugs with Lingzhi were cisplatin, 5-fluorouracil (5-FU) and paclitaxel, whereas Tegafur/uracil (UFT)/Tegafur, 5-FU, and mitomycin were the ones used more often with Yunzhi. Only two clinical pharmacokinetic studies were available showing no significant interactions between Polysaccharide K (PSK) and Tegafur. From the pharmacodynamic interactions perspective, combination uses of Yunzhi/Lingzhi with cytotoxic drugs in clinical practice could lead to improvement in survival (n = 31) and quality of life (n = 17), reduction in tumor lesions (n = 22), immune modulation (n = 38), and alleviation of chemotherapy-related side effects (n = 14) with no reported adverse effects.

Conclusion

Our findings suggest that the clinical combination use of Lingzhi or Yunzhi with cytotoxic drugs could enhance the efficacy and ameliorate the adverse effects of cytotoxic drugs, leading to improved quality of life in cancer patients. More high quality clinical studies including pharmacokinetic herb-drug interactions studies are warranted to verify these observations and mechanisms involved. Based on the high quality clinical data, pharmacoepidemiology methods and bioinformatics or data mining could be adopt for further identification of clinical meaningful herb-drug interactions in cancer therapies.
Cortactin deacetylation by HDAC6 and SIRT2 regulates neuronal migration and dendrite morphogenesis during cerebral cortex development
Authors: Kim Ji-ye , Hwang Hee-Gon , Lee Joo-Yong , Kim Minkyu , Kim Jeong-Yoon
Published: July 2020

Abstracts

Proper dendrite morphogenesis and neuronal migration are crucial for cerebral cortex development and neural circuit formation. In this study, we sought to determine if the histone deacetylase HDAC6 plays a role in dendrite development and neuronal migration of pyramidal neurons during cerebral cortex development. It was observed that knockdown of HDAC6 leads to defective dendrite morphogenesis and abnormal Golgi polarization in vitro, and the expression of wild type cortactin or deacetyl-mimetic cortactin 9KR rescued the defective phenotypes of the HDAC6 knockdown neurons. This suggests that HDAC6 promotes dendritic growth and Golgi polarization through cortactin deacetylation in vitro. We also demonstrated that ectopic expression of SIRT2, a cytoplasmic NAD+ − dependent deacetylase, suppresses the defects of HDAC6 knockdown neurons. These results indicate that HDAC6 and SIRT2 may be functionally redundant during dendrite development. Neurons transfected with both HDAC6 and SIRT2 shRNA or acetyl-mimetic cortactin 9KQ showed slow radial migration compared to the control cells during cerebral cortex development. Furthermore, a large portion of cortactin 9KQ-expressing pyramidal neurons at layer II/III in the cerebral cortex failed to form an apical dendrite toward the pial surface and had an increased number of primary dendrites, and the percentage of neurons with dendritic Golgi decreased in cortactin 9KQ-expressing cells, compared to control neurons. Taken together, this study suggests that HDAC6 and SIRT2 regulate neuronal migration and dendrite development through cortactin deacetylation in vivo.
LncRNA CTBP1-AS2 regulates miR-216a/ PTEN to suppress ovarian cancer cell proliferation
Authors: Cui Kaiying , Zhu Genhai
Published: July 2020

Background

We analyzed TCGA dataset and observed the downregulation of CTBP1-AS2 in ovarian cancer (OC), while the function of CTBP1-AS2 has only been investigated in diabetes and cardiomyocyte hypertrophy, but not in cancer biology. We therefore analyzed the involvement of CTBP1-AS2 in OC.

Result

We found that CTBP1-AS2 was downregulated in OC and predicted poor survival. CTBP1-AS2 in luciferase activity assay interacted with miR-216a, while overexpression of CTBP1-AS2 and miR-216a had no significant effects on the expression of each other. However, increased expression level of PTEN, a target of miR-216a, was observed after CTBP1-AS2 overexpression. Increased proliferation rate of OC cells was observed after the overexpression of miR-216a. CTBP1-AS2 and PTEN overexpression resulted in the reduced proliferation rate of OC cells and reduced effects of miR-216a overexpression.

Conclusion

CTBP1-AS2 regulates miR-216a/PTEN to suppress OC cell proliferation.
Mechanical chest compression devices in the helicopter emergency medical service in Switzerland
Authors: Pietsch Urs , Reiser David , Wenzel Volker , Knapp Jürgen , Tissi Mario , Theiler Lorenz , Rauch Simon , Meuli Lorenz , Albrecht Roland
Published: July 2020

Background

Over the past years, several emergency medical service providers have introduced mechanical chest compression devices (MCDs) in their protocols for cardiopulmonary resuscitation (CPR). Especially in helicopter emergency medical systems (HEMS), which have limitations regarding loading weight and space and typically operate in rural and remote areas, whether MCDs have benefits for patients is still unknown. The aim of this study was to evaluate the use of MCDs in a large Swiss HEMS system.

Materials and methods

We conducted a retrospective observational study of all HEMS missions of Swiss Air rescue Rega between January 2014 and June 2016 with the use of an MCD (Autopulse®). Details of MCD use and patient outcome are reported from the medical operation journals and the hospitals’ discharge letters.

Results

MCDs were used in 626 HEMS missions, and 590 patients (94%) could be included. 478 (81%) were primary missions and 112 (19%) were interhospital transfers. Forty-nine of the patients in primary missions were loaded under ongoing CPR with MCDs. Of the patients loaded after return of spontaneous circulation (ROSC), 20 (7%) experienced a second CA during the flight. In interhospital transfers, 102 (91%) only needed standby use of the MCD. Five (5%) patients were loaded into the helicopter with ongoing CPR. Five (5%) patients went into CA during flight and the MCD had to be activated. A shockable cardiac arrhythmia was the only factor significantly associated with better survival in resuscitation missions using MCD (OR 0.176, 95% confidence interval 0.084 to 0.372,p < 0.001).

Conclusion

We conclude that equipping HEMS with MCDs may be beneficial, with non-trauma patients potentially benefitting more than trauma patients.
Probiotics’ efficacy in paediatric diseases: which is the evidence? A critical review on behalf of the Italian Society of Pediatrics
Authors: Martinelli Massimo , Banderali Giuseppe , Bobbio Marisa , Civardi Elisa , Chiara Alberto , D’Elios Sofia , Lo Vecchio Andrea , Olivero Mattia , Peroni Diego , Romano Claudio , Stronati Mauro , Turra Renato , Viola Irene , Staiano Annamaria , Villani Alberto
Published: July 2020

During the last decade several paediatric studies have been published with different possible indications for probiotics, leading to a global increase of probiotics’ market. Nevertheless, different study designs, multiple single/combined strains and small sample size still leave many uncertainties regarding their efficacy. In addition, different regulatory and quality control issues make still very difficult the interpretation of the clinical data. The objective of this review is to critically summarise the current evidence on probiotics’ efficacy and safety on a different number of pathologies, including necrotizing enterocolitis, acute infectious diarrhoea, allergic diseases and functional gastrointestinal disorders in order to guide paediatric healthcare professionals on using evidence-based probiotics’ strains. To identify relevant data, literature searches were performed including Medline-PubMed, the Cochrane Library and EMBASE databases. Considering probiotics strain-specific effects, the main focus was on individual probiotic strains and not on probiotics in general.
Proposal for a new therapeutic high dosage of Pidotimod in children with periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome: a randomized controlled study
Authors: Manti Sara , Filosco Federica , Parisi Giuseppe Fabio , Finocchiaro Giuseppe Germano , Papale Maria , Giugno Andrea , Barone Patrizia , Leonardi Salvatore
Published: July 2020

Background

Despite to PFAPA syndrome is considered a benign and self-limited condition in childhood its impact on patients and families can be remarkable in many cases. Currently, the therapeutic options for managing are non-specific and no consensus exists about the best treatment to use. Pidotimod has been suggested as a new potential treatment in PFAPA syndrome for its immunodulatory effects. We conducted a preliminary, prospective, controlled, open, cross-over trial to assess the efficacy and the safety of Pidotimod in the treatment of children with PFAPA syndrome.

Methods

22 children with PFAPA syndrome were randomly allocated to treatment with pidotimod (with 2 vials of 400 mg daily) in combination with betamethasone 0.5–1 mg on need, based on parents/caregivers’ decision (group A) or betamethasone 0.5-1 mg on need, based on parents/caregivers’ decision (group B). Each treatment period was for 3 months (Phase 1), after that patients were switched to the other arm for other 3 months (Phase 2). Efficacy was expressed in terms of number of episodes of fever, pharyngitis, or aphthous stomatitis, as well as the additional use of betamethasone on need. Safety and tolerability of the Pidotimod were evaluated on the basis of the number and type of adverse events (AEs) recorded during the treatment.

Results

Patients receiving Pidotimod and use betametasone showed a significant decrease in frequency of fevers (p = 0.002); number of episodes of pharyngitis (p = 0.049); aphthous stomatitis (p = 0.036) as well as the betamethasone use on need (p = 0.007). Overall, 19/22 (86.4%) showed benefits from Pidotimod administration. The safety profile of Pidotimod was excellent as no serious adverse events have been reported in the treated groups.

Conclusions

We firstly showed that high dosage of Pidotimod could be an effective and safe to reduce the PFAPA attacks in children.
Expression levels of circulating miRNAs as biomarkers during multimodal treatment of rectal cancer - TiMiSNAR-mirna: a substudy of the TiMiSNAR Trial (NCT03962088)
Authors: Monsellato Igor , Garibaldi Elisabetta , Cassinotti Elisa , Baldari Ludovica , Boni Luigi , Elmore Ugo , Delpini Roberto , Rosati Riccardo , Perinotti Roberto , Alongi Filippo , Bertocchi Elisa , Gori Stefania , Ruffo Giacomo , Pernazza Graziano , Pulighe Fabio , De Nisco Carlo , Morpurgo Emilio , Contardo Tania , Mammano Enzo , Perna Federico , Menegatti Benedetta , Coratti Andrea , Buccianti Piero , Balestri Riccardo , Ceccarelli Cristina , Cavaliere Davide , Solaini Leonardo , Ercolani Giorgio , Traverso Elena , Fusco Vittorio , Torri Valter , Orecchia Sara
Published: July 2020

Background

Neoadjuvant chemoradiotherapy followed by surgery is the mainstay treatment for locally advanced rectal cancer, leading to significant decrease in tumor size (downsizing) and a shift towards earlier disease stage (downstaging). Extensive histopathological work-up of the tumor specimen after surgery including tumor regression grading and lymph node status helped to visualize individual tumor sensitivity to chemoradiotherapy, retrospectively. As the response to neoadjuvant chemoradiotherapy is heterogeneous, however, valid biomarkers are needed to monitor tumor response. A relevant number of studies aimed to identify molecular markers retrieved from tumor tissue while the relevance of blood-based biomarkers is less stringent assessed. MicroRNAs are currently under investigation to serve as blood-based biomarkers. To date, no screening approach to identify relevant miRNAs as biomarkers in blood of patients with rectal cancer was undertaken. The aim of the study is to investigate the role of circulating miRNAs as biomarkers in those patients included in the TiMiSNAR Trial (NCT 03465982). This is a biomolecular substudy of TiMiSNAR Trial (NCT03962088).

Methods

All included patients in the TiMiSNAR Trial are supposed to undergo blood collection at the time of diagnosis, after neoadjuvant treatment, after 1 month from surgery, and after adjuvant chemotherapy whenever indicated.

Discussion

TiMiSNAR-MIRNA will evaluate the association of variation between preneoadjuvant and postneoadjuvant expression levels of miRNA with pathological complete response. Moreover, the study will evaluate the role of liquid biopsies in the monitoring of treatment, correlate changes in expression levels of miRNA following complete surgical resection with disease-free survival, and evaluate the relation between changes in miRNA during surveillance and tumor relapse.

Trial registration

Clinicaltrials.gov NCT03962088. Registered on 23 May 2019.
Efficacy of acupuncture for treatment of intermittent claudication in patients with degenerative lumbar spinal stenosis: protocol for a randomized controlled trial
Authors: Zhou Jing , Liu Sixing , Sun Yuanjie , Wang Weiming , Liu Zhishun
Published: July 2020

Background

Degenerative lumbar spinal stenosis (DLSS) is a common condition secondary to degenerative changes. Acupuncture may be effective for treating DLSS. However, there is a lack of sufficient evidence showing the efficacy of acupuncture. The aim of this study is to assess the efficacy and safety of acupuncture for relieving neurogenic claudication in patients with DLSS.

Methods

A total of 196 patients will be randomly assigned to an acupuncture group or a sham acupuncture group at a ratio of 1:1. Patients will receive 18 sessions of treatment for 6 continuous weeks. The primary outcome will be the change in the Modified Roland-Morris Disability Questionnaire score from baseline to week 6. The secondary outcomes will include the change in the scores from baseline for the Numerical Rating Scale, Swiss Spinal Stenosis Questionnaire, and Anxiety and Depression Scale. Additionally, the expectancy of acupuncture, blinding, and safety will also be assessed. All analysis will be performed based on intention-to-treat.

Discussion

The aim of this study is to evaluate the efficacy and safety of acupuncture for the treatment of neurogenic claudication in patients with DLSS. A limitation of this study is that acupuncturists cannot be blinded according to the characteristics of acupuncture, which may introduce some bias.

Trial registration

ClinicalTrials.gov NCT03784729 and protocol ID 2018-161-KY. Registered on 18 December 2018.
A single early-in-life antibiotic course increases susceptibility to DSS-induced colitis
Authors: Ozkul Ceren , Ruiz Victoria E. , Battaglia Thomas , Xu Joseph , Roubaud-Baudron Claire , Cadwell Ken , Perez-Perez Guillermo I. , Blaser Martin J.
Published: July 2020

Background

There is increasing evidence that the intestinal microbiota plays a crucial role in the maturation of the immune system and the prevention of diseases during childhood. Early-life short-course antibiotic use may affect the progression of subsequent disease conditions by changing both host microbiota and immunologic development. Epidemiologic studies provide evidence that early-life antibiotic exposures predispose to inflammatory bowel disease (IBD).

Methods

By using a murine model of dextran sodium sulfate (DSS)-induced colitis, we evaluated the effect on disease outcomes of early-life pulsed antibiotic treatment (PAT) using tylosin, a macrolide and amoxicillin, a beta-lactam. We evaluated microbiota effects at the 16S rRNA gene level, and intestinal T cells by flow cytometry. Antibiotic-perturbed or control microbiota were transferred to pups that then were challenged with DSS.

Results

A single PAT course early-in-life exacerbated later DSS-induced colitis by both perturbing the microbial community and altering mucosal immune cell composition. By conventionalizing germ-free mice with either antibiotic-perturbed or control microbiota obtained 40 days after the challenge ended, we showed the transferrable and direct effect of the still-perturbed microbiota on colitis severity in the DSS model.

Conclusions

The findings in this experimental model provide evidence that early-life microbiota perturbation may increase risk of colitis later in life.
Therapeutic potential of CKD-506, a novel selective histone deacetylase 6 inhibitor, in a murine model of rheumatoid arthritis
Authors: Park Jin Kyun , Jang Yu Jin , Oh Bo Ram , Shin Jieun , Bae Daekwon , Ha Nina , Choi Young il , Youn Gi Soo , Park Jinseu , Lee Eun Young , Lee Eun Bong , Song Yeong Wook
Published: July 2020

Objectives

Histone deacetylase (HDAC) 6 promotes inflammation. We investigated the anti-arthritic effects of CKD-506, a novel HDAC6 inhibitor, in vitro and in a murine model of arthritis as a novel treatment option for rheumatoid arthritis (RA).

Methods

HDAC6 was overexpressed in mouse peritoneal macrophages and RAW 264.7 cells, and the effects of a HDAC6 inhibitor CKD-506 on cytokine production and activity of NF-κB and AP-1 signaling were examined. Peripheral blood mononuclear cells (PBMCs) from RA patients and fibroblast-like synoviocytes (FLS) were activated in the presence of CKD-506. Next, regulatory T cells (Tregs) were induced from RA patients and co-cultured with healthy effector T cells (Teffs) and cell proliferation was analyzed by flow cytometry. Finally, the effects of the inhibitor on the severity of arthritis were assessed in a murine model of adjuvant-induced arthritis (AIA).

Results

Overexpression of HDAC6 induced macrophages to produce TNF-α and IL-6. The inhibitory effect of CKD-506 was mediated via blockade of NF-κB and AP-1 activation. HDAC6 inhibition reduced TNF-α and IL-6 production by activated RA PBMCs. CKD-506 inhibited production of MMP-1, MMP-3, IL-6, and IL-8 by activated FLS. In addition, CKD-506 inhibited proliferation of Teffs directly and indirectly by improving iTreg function. In AIA rats, oral CKD-506 improved clinical arthritis in a dose-dependent manner. A combination of sub-therapeutic CKD-506 and methotrexate exerted a synergistic effect.

Conclusion

The novel HDAC6 inhibitor CKD-506 suppresses inflammatory responses by monocytes/macrophages, improves Treg function, and ameliorates arthritis severity in a murine model of RA. Thus, CKD-506 might be a novel and effective treatment option for RA.
The effect of increasing heel height on lower limb symmetry during the back squat in trained and novice lifters
Authors: Sayers Mark G. L. , Hosseini Nasab S. H. , Bachem Caroline , Taylor William R. , List Renate , Lorenzetti Silvio
Published: July 2020

Background

Symmetry during lifting is considered critical for allowing balanced power production and avoidance of injury. This investigation assessed the influence of elevating the heels on bilateral lower limb symmetry during loaded (50% of body weight) high-bar back squats.

Methods

Ten novice (mass 67.6 ± 12.4 kg, height 1.73 ± 0.10 m) and ten regular weight trainers (mass 66.0 ± 10.7 kg, height 1.71 ± 0.09 m) were assessed while standing on both the flat level floor and on an inclined board. Data collection used infra-red motion capture procedures and two force platforms to record bilateral vertical ground reaction force (GRFvert) and ankle, knee and hip joint kinematic and kinetic data. Paired t-tests and statistical parametric mapping (SPM1D) procedures were used to assess differences in discrete and continuous bilateral symmetry data across conditions.

Results

Although discrete joint kinematic and joint moment symmetry data were largely unaffected by raising the heels, the regular weight trainers presented greater bilateral asymmetry in these data than the novices. The one significant finding in these discrete data showed that raising the heels significantly reduced maximum knee extension moment asymmetry (P = 0.02), but in the novice group only. Time-series analyses indicated significant bilateral asymmetries in both GRFvert and knee extension moments mid-way though the eccentric phase for the novice group, with the latter unaffected by heel lift condition. There were no significant bilateral asymmetries in time series data within the regular weight training group.

Conclusions

This investigation highlights that although a degree of bilateral lower limb asymmetry is common in individuals performing back squats, the degree of this symmetry is largely unaffected by raising the heels. Differences in results for discrete and time-series symmetry analyses also highlight a key issue associated with relying solely on discrete data techniques to assess bilateral symmetry during tasks such as the back squat.
The effects of intravitreal adalimumab injection on pseudophakic macular edema
Authors: Farvardin Mohsen , Namvar Ehsan , Sanie-Jahromi Fatemeh , Johari Mohammad Karim
Published: July 2020

Objective

Pseudophakic macular edema is a frequent complication following cataract surgery. Inflammation is a major etiologic factor in the development of pseudophakic cystoid macular edema. Tumor necrosis factor-alpha has an important role in ocular inflammation. Adalimumab (Humira) is an inhibitor of tumor necrosis factor-alpha that has been approved in the United States. An open-label, uncontrolled, prospective, interventional study of five consecutive patients (5 eyes) with cystoid macular edema who were treated with off-label intravitreal adalimumab at Khalili Hospital was conducted. Slit-lamp examination and optical coherence tomography were done for all patients.

Results

No statistically significant difference was detected between best corrected visual acuity and central macular thickness before and after injection in pseudophakic macular edema. One patient developed uveitis approximately 2 weeks after injection. Based on the results, adalimumab does not appear to be an effective treatment for pseudophakic macular edema, and it may cause uveitis. Caution should be exercised when using this drug.

Trial registration Iranian Registry of Clinical Trials IRCT2016100430130N1, 2016.12.03, Retrospectively registered
Effects of different abiotic stresses on carotenoid and fatty acid metabolism in the green microalga Dunaliella salina Y6
Authors: Wu Mingcan , Zhu Rongfang , Lu Jiayang , Lei Anping , Zhu Hui , Hu Zhangli , Wang Jiangxin
Published: July 2020

Purpose

Under different abiotic-stress conditions, the unicellular green microalga Dunaliella salina accumulates large amounts of carotenoids which are accompanied by fatty acid biosynthesis. Carotenoids and fatty acids both possess long carbon backbones; however, the relationship between carotenoid and fatty acid metabolism is controversial and remains poorly understood in microalgae.

Methods

In this study, we investigated the growth curves and the β-carotene, lutein, lipid, and fatty acid contents of D. salina Y6 grown under different abiotic-stress conditions, including high light, nitrogen depletion, and high salinity.

Results

Both high-salinity and nitrogen-depleted conditions significantly inhibited cell growth. Nitrogen depletion significantly induced β-carotene accumulation, whereas lutein production was promoted by high light. The accumulation of lipids did not directly positive correlate with β-carotene and lutein accumulation under the three tested abiotic-stress conditions, and levels of only a few fatty acids were increased under specific conditions.

Conclusion

Our data indicate that cellular β-carotene accumulation in D. salina Y6 positive correlates with accumulation of specific fatty acids (C16:0, C18:3n3, C14:0, and C15:0) rather than with total fatty acid content under different abiotic stress conditions.
Respective stemness and chondrogenic potential of mesenchymal stem cells isolated from human bone marrow, synovial membrane, and synovial fluid
Authors: Neybecker Paul , Henrionnet Christel , Pape Elise , Grossin Laurent , Mainard Didier , Galois Laurent , Loeuille Damien , Gillet Pierre , Pinzano Astrid
Published: July 2020

Background

MSCs isolated from bone marrow (BM-MSCs) have well-established chondrogenic potential, but MSCs derived from the synovial membrane (SM-MSCs) and synovial fluid (SF-MSCs) are thought to possess superior chondrogenicity. This study aimed to compare the in vitro immunophenotype and trilineage and chondrogenic potential of BM-MSCs to SM-MSCs and SF-MSCs.

Methods

MSCs were isolated from bone marrow (BM-MSCs), synovial membrane (SM-MSCs), and synovial fluid (SF-MSCs) extracted from the hips (BM) and knees (SM and SF) of advanced OA patients undergoing arthroplasty. Flow cytometric analysis was used at P2 to evaluate cell stemness. The trilinear differentiation test was performed at P2. At P3, MSC-seeded collagen sponges were cultured in chondrogenic medium for 28 days. Chondrogenic gene expression was quantified by qRT-PCR. Finally, the implants were stained to assess the deposition of proteoglycans and type II collagen.

Results

Despite variability, the immunophenotyping of BM-MSCs, SM-MSCs, and SF-MSCs was quite similar. All cell types were positive for the expression of stem cell markers and negative for exclusion markers. Additionally, chondrogenic differentiation and hypertrophy were more pronounced in BM-MSCs (ACAN,SOX9,COL2B, andCOL10A) than in SF-MSCs, with SM-MSCs having intermediate characteristics. Concerning matrix synthesis, the three cell types were equipotent in terms of GAG content, while BM-MSC ECM synthesis of type II collagen was superior.

Conclusions

Chondrogenic MSCs are easily collected from SM and SF in advanced human OA, but in vitro chondrogenesis that is superior to age-matched BM-MSCs should not be expected. However, due to intra-articular priming, SF-MSCs did not overexpress hypertrophic gene.
Transcriptional profiling reveals altered biological characteristics of chorionic stem cells from women with gestational diabetes
Authors: Chen Liyun , Wang Chung-Teng , Forsyth Nicholas R. , Wu Pensee
Published: July 2020

Background

Gestational diabetes (GDM) is a common complication of pregnancy. The impact of pregnancy complications on placental function suggests that extraembryonic stem cells in the placenta may also be affected during pregnancy. Neonatal tissue-derived stem cells, with the advantages of their differentiation capacity and non-invasive isolation processes, have been proposed as a promising therapeutic avenue for GDM management through potential cell therapy approaches. However, the influence of GDM on autologous stem cells remains unclear. Thus, studies that provide comprehensive understanding of stem cells isolated from women with GDM are essential to guide future clinical applications.

Methods

Human chorionic membrane-derived stem cells (CMSCs) were isolated from placentas of healthy and GDM pregnancies. Transcriptional profiling was performed by DNA microarray, and differentially regulated genes between GDM- and Healthy-CMSCs were used to analyse molecular functions, differentiation, and pathway enrichment. Altered genes and biological functions were validated via real-time PCR and in vitro assays.

Results

GDM-CMSCs displayed, vs. Healthy-CMSCs, 162 upregulated genes associated with increased migration ability, epithelial development, and growth factor-associated signal transduction while the 269 downregulated genes were strongly linked to angiogenesis and cellular metabolic processes. Notably, significantly reduced expression of detoxification enzymes belonging to the aldehyde dehydrogenase gene families (ALDH1A1/1A2, ALDH2, ALDH3) accounted for downregulation across several metabolic pathways. ALDH activity and inhibitor assays indicated that reduced gene expression of ALDHs affected ALDH enzymatic functions and resulted in oxidative stress dysregulation in GDM-CMSCs.

Conclusion

Our combined transcriptional analysis and in vitro functional characterisation have provided novel insights into fundamental biological differences in GDM- and Healthy-CMSCs. Enhanced mobility of GDM-CMSCs may promote MSC migration toward injured sites; however, impaired cellular metabolic activity may negatively affect any perceived benefit.
MicroRNA-503-3p affects osteogenic differentiation of human adipose-derived stem cells by regulation of Wnt2 and Wnt7b under cyclic strain
Authors: Luo Yadong , Ding Xu , Ji Huan , Li Meng , Song Haiyang , Li Sheng , Wang Chenxing , Wu Heming , Du Hongming
Published: July 2020

Background

MicroRNAs (miRNAs) play a role in regulating osteogenic differentiation (OD) of mesenchymal stem cells by inhibiting mRNAs translation under cyclic strain. miR-503-3p was downregulated in OD of human adipose-derived stem cells (hASCs) in vivo under cyclic strain in our previous study, while it might target the Wnt/β-catenin (W-β) pathway. In this study, we explored miR-503-3p’s role in OD of hASCs under cyclic strain.

Methods

OD of hASCs was induced by cyclic strain. Bioinformatic and dual luciferase analyses were used to confirm the relationship between Wnt2/Wnt7b and miR-503-3p. Immunofluorescence was used to detect the effect of miR-503-3p on Wnt2/Wnt7b and β-catenin in hASCs transfected with miR-503-3p mimic and inhibitor. Mimic, inhibitor, and small interfering RNA (siRNA) transfected in hASCs to against Wnt2 and Wnt7b. Quantitative real-time PCR (RT-PCR) and western blot were used to examine the OD and W-β pathway at the mRNA and protein levels, respectively. Immunofluorescence was performed to locate β-catenin. ALP activity and calcium were detected by colorimetric assay.

Results

Results of immunophenotypes by flow cytometry and multi-lineage potential confirmed that the cultured cells were hASCs. Results of luciferase reporter assay indicated that miR-503-3p could regulate the expression levels of Wnt2 and Wnt7b by targeting their respective 3′-untranslated region (UTR). Under cyclic strain, gain- or loss-function of miR-503-3p studies by mimic and inhibitor revealed that decreasing expression of miR-503-3p could significantly bring about promotion of OD of hASCs, whereas increased expression of miR-503-3p inhibited OD. Furthermore, miR-503-3p high-expression reduced the activity of the W-β pathway, as indicated by lowering expression of Wnt2 and Wnt7b, inactive β-catenin in miR-503-3p-treated hASCs. By contrast, miR-503-3p inhibition activated the W-β pathway.

Conclusions

Collectively, our findings indicate that miR-503-3p is a negative factor in regulating W-β pathway by Wnt2 and Wnt7b, which inhibit the OD of hASCs under cyclic strain.