bluuebunny/crossref_metadata_2025 huggingface dataset:
Indications and diagnostic yield of small-bowel capsule endoscopy in a real-world setting
Authors: Kharazmi André Artan , Aslani Saeid , Kristiansen Malene Fey , Dahl Eva Efsen , Berner-Hansen Mark
Published: June 2020

Background

Indications and diagnostic yield of small-bowel video capsule endoscopy (SB-VCE) are communicated in recent clinical academic guidelines. However, guidelines are based mainly on relatively few, small, selection-biased studies at experienced centers, and thus we lack information on indications and diagnostic yield of SB-VCE in the real-world community setting. The aim of the study was to evaluate indications and diagnostic yield of SB-VCE in the real-world community setting.

Methods

Our local VCE clinical database was used to identify patients undergoing SB-VCE procedures over a 7-year period (2011–2018). Patients were broadly referred and underwent SB-VCE using PillCam™ SB 2 and SB 3 capsule systems. Procedures were reviewed by local endoscopists, who had undergone similar formal SB-VCE review training. Medical reports of the procedures were composed as such. We retrospectively reviewed all reports and gathered data regarding indications and findings. Diagnostic yield was considered positive if SB-VCE visualized any type of clinically significant pathological finding.

Results

536 SB-VCE procedures in 516 patients were included in final assessment. Patient mean (± SD) age was 50 ± 20 years with approximately even female/male ratio (275:241). The overall proportion of positive findings was 42% (225/536). The two main indications were obscure gastrointestinal bleeding (occult/anemia or overt/active, OGIB) of 46% (246/536) and definite/suspected Crohn’s disease (CD) of 39% (210/536). Positive SB-VCE findings were obtained in 44% (108/246) of procedures with indication of OGIB and in 50% (104/210) of procedures with indication of CD.

Conclusions

The indications for SB-VCE are largely consistent with guidelines but with an apparently relatively low diagnostic yield in our real-world community setting.
“Study protocol for the ≥65 years NOrthern jutland Cohort of Fall risk Assessment with Objective measurements (the NOCfao study)”
Authors: Villumsen Morten , Grarup Bo , Christensen Steffan Wittrup Mc Phee , Palsson Thorvaldur Skuli , Hirata Rogerio Pessoto
Published: June 2020

Background

Accidental falls are common among community-dwellers, probably due to the level of physical activity and impaired postural stability. Today, fall risk prediction tools’ discriminative validity are only moderate. In order to increase the accuracy, multiple variables such as highly validated objective field measurements of physical activity and impaired postural stability should be adressed in order to predict falls. The main aim of this paper is to describe the ≥65 years NOrthern jutland Cohort of Fall risk Assessment with Objective measurements (NOCfao) investigating the association between physical activity and impaired postural stability and the risk of fall episodes among community-dwelling older adults.

Methods

The study consists of a baseline session where the participants are asked to respond to three questionnaires, perform physical tests (i.e., measuring strength in the upper and lower extremities, balance, and walking speed), participate in an assessment of pain sensitivity, and to wear an ankle mounted pedometer for measuring physical activity for 5 days. Subsequently, the fall incidences and the circumstances surrounding the falls during the previous 1 to 2 months will be recorded throughout a one-year follow-up period.

Discussion

This study will add to the present-day understanding of the association between physical activity and impaired postural stability and the risk of fall episodes among community-dwelling older adults. These data will provide valid and reliable information on the relationship between these variables and their significance for community-dwelling older adults.

Trial registration

ClinicalTrials.gov identifier: NCT2995317. Registered December 13th, 2016.
A Chinese case of Nakajo–Nishimura syndrome with novel compound heterozygous mutations of the PSMB8 gene
Authors: Jia Tao , Zheng Yi , Feng Cheng , Yang Tielin , Geng Songmei
Published: June 2020

Background

Nakajo-Nishimura syndrome (NNS) is an autosomal recessive heredity disorder, one of a spectrum of autoinflammatory diseases named proteasome-associated autoinflammatory syndrome (PRAAS) caused by mutations of PSMB8 gene. NNS is characterized by pernio-like skin rashes, intermittent fever, and long clubbed fingers and toes with joint contractures, partially with progressive lipomuscular atrophy, emaciation, hepatosplenomegaly and basal ganglion calcification.

Case presentation

We presented a sporadic case of NNS with compound heterozygous mutations in the PSMB8 gene. The 4-year-old boy was affected by progressive erythematous plaques on his nose and gradually involved hands and feet later with characteristic appearance of long clubbed fingers. The repetitive periodic intermittent fever was recorded. By gene sequencing, novel compound heterozygous mutations c.373C > T (p.R125C) and c.355G > A (p.D119N) in the PSMB8 gene were found. The patient responded well to low dosage of oral methylprednisolone.

Conclusions

We reported novel compound heterozygous mutations in PSMB8 in a sporadic Chinese NNS patient.
The morphological characteristics of hippocampus and thalamus in mesial temporal lobe epilepsy
Authors: Wu Dongyan , Chang Feiyan , Peng Dantao , Xie Sheng , Li Xiaoxuan , Zheng Wenjing
Published: June 2020

Background

Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy, which is frequently characterized by hippocampal sclerosis (HS). Accumulating studies have suggested widespread cortico-cortical connections related to MTLE. The role of subcortical structures involved in general epilepsy has been extensively investigated, but it is still limited in MTLE. Our purpose was to determine the specific morphological correlation between sclerotic hippocampal and thalamic sub-regions, using quantitative analysis, in MTLE.

Methods

In this study, 23 MTLE patients with unilateral hippocampal sclerosis and 24 healthy controls were examined with three-dimensional T1 MRI. Volume quantitative analysis in the hippocampus and thalamus was conducted and group-related volumetric difference was assessed. Moreover, vertex analysis was further performed using automated software to delineate detailed morphological patterns of the hippocampus and thalamus. The correlation was used to examine whether there is a relationship between volume changes of two subcortical structures and clinical characteristics.

Results

The patients had a significant volume decrease in the sclerotic hippocampus (p < 0.001). Compared to controls, obvious atrophic patterns were observed in the bilateral hippocampus in MTLE (p < 0.05). Only small patches of shrinkage were noted in the bilateral thalamus (p < 0.05). Moreover, the volume change of the hippocampus had a significant positive correlation with that of the thalamus (P < 0.001). Intriguingly, volume changes of the hippocampus and thalamus were correlated with the duration of epilepsy (hippocampus: P = 0.024; thalamus: P = 0.022). However, only volume changes of thalamus possibly differentiated between two prognostic groups in patients (P = 0.026).

Conclusions

We demonstrated the morphological characteristics of the hippocampus and thalamus in MTLE, providing new insights into the interrelated mechanisms between the hippocampus and thalamus, which have potential clinical significance for refining neuromodulated targets.
Bilateral multiple serous retinal detachments after treatment with nivolumab: a case report
Authors: Miyamoto Reina , Nakashizuka Hiroyuki , Tanaka Koji , Wakatsuki Yu , Onoe Hajime , Mori Ryusaburo , Kawamura Akiyuki
Published: June 2020

Background

Immune checkpoint inhibitors have recently been widely used for advanced cancers and are known to cause ocular complications. We herein report a case developing bilateral serous retinal detachments, without ocular inflammation, after starting nivolumab treatment.

Case presentation

A 73-year-old man was referred to our hospital, having become aware of metamorphopsia 2 months after starting nivolumab (anti-programmed cell death protein 1 monoclonal antibody) for malignant melanoma of the nasal cavity. The initial corrected visual acuity of the right eye was 20/20, and that of the left eye was 20/16. There were no inflammatory findings in the anterior segment or the vitreous. Vitelliform lesions were found in the macular area of both ocular fundi, consistent with serous retinal detachment and subretinal deposits. Swept source optical coherence tomography showed diffuse thickening of the outer photoreceptor segment and thickening of the choroid. Two months after the initial diagnosis, multiple vitelliform lesions were noted, and the fundus findings had worsened. Indocyanine green fluorescein angiography showed delayed inflow in the peripapillary and posterior pole regions in the early phase of imaging. Fundus autofluorescence showed hyperautofluorescence consistent with most of the vitelliform lesions on color fundus photography.

Conclusions

Nivolumab may have impaired the pumping and phagocytosis functions of retinal pigment epithelial cells, resulting in bilateral serous retinal detachments and thickening of the photoreceptor outer segment. This is the first case report, to our knowledge, describing multiple bilateral serous retinal detachments and outer segment thickening without inflammation in a patient treated with nivolumab.
Femoral migration of the cementless Oxford which caused the bearing dislocation: a report of two cases
Authors: Inui Hiroshi , Taketomi Shuji , Yamagami Ryota , Kawaguchi Kohei , Tanaka Sakae
Published: June 2020

Background

There are no previous reports on the complications around the femoral component of cementless Oxford unicompartmental knee arthroplasty (UKA). However, we experienced two cases of femoral migration to the proximal side, which caused bearing dislocations after cementless Oxford UKA.

Case presentation

Case1. In an 82-year-old woman, bearing dislocation occurred 13 months postoperatively because of femoral migration that was resolved with an revision surgery to cemented component and thicker mobile insert.

Case2. In a 52-year-old man, first bearing dislocation occurred 7 months postoperatively. Five months after revising the insert to a thicker one, another dislocation occurred mainly because of the femoral migration. Eventually, a revision to total knee arthroplasty was necessary.

Conclusions

The inferred main reasons of femoral migration of cementless Oxford were osteoporosis for the first case and early return to high performance sports activity for the second case. Although several merits of using cementless prosthesis, particularly better fixation and lesser radiolucency than cemented prosthesis, have been reported, surgeons should pay attention to the patient’s bone quality and advise a slow return to high-level physical activity.
Chemopreventive effect of Betulinic acid via mTOR -Caspases/Bcl2/Bax apoptotic signaling in pancreatic cancer
Authors: Guo Yangyang , Zhu Hengyue , Weng Min , Wang Cheng , Sun Linxiao
Published: June 2020

Background

Pancreatic cancer is aggressive with no symptoms until the advanced stage reached. The increased resistance of pancreatic cancer to chemotherapy demonstrates a dilemma in the clinical field. Hence, it is a matter of great urgency to develop an effective drug to treat patients with pancreatic cancer. Betulinic acid is a major triterpene isolated from spina date seed. Several studies have suggested its low toxicity and side effects to patients with malaria and inflammation. However, relevant studies on betulinic acid in inhibiting cancer were insufficient and the molecular mechanism was unclear. This study aimed to systematically explore the potential anti-cancer functions of betulinic acid in pancreatic cancer, and investigate its underlying molecular mechanism.

Methods

The Counting Kit-8 assay, colony formation, transwell invasion assay, wound healing assay, flow cytometry and xenograft nude mice model were used to evaluate the effect of betulinic acid on the proliferation, invasion and migration ability of pancreatic cancer cells.

Results

Our results showed that betulinic acid obviously suppressed pancreatic cancer both in vitro and in vivo in a dose-dependent manner. We also determined that betulinic acid inhibited pancreatic cancer by specifically targeting mTOR signaling rather than Nrf2 or JAK2.

Conclusions

These findings clarify that betulinic acid is a potential and valuable anticancer agent for pancreatic cancer, and indicate the specific molecular target of betulinic acid.
The impacts of quality improvement on maternal and newborn health: preliminary findings from a health system integrated intervention in four Ethiopian regions
Authors: Hagaman Ashley K. , Singh Kavita , Abate Mehiret , Alemu Haregeweyni , Kefale Abera Biadgo , Bitewulign Befikadu , Estifanos Abiy Seifu , Kiflie Abiyou , Mulissa Zewdie , Tiyo Hillina , Seman Yakob , Tadesse Meseret Zelalem , Magge Hema
Published: June 2020

Background

Quality improvement (QI) methods are effective in improving healthcare delivery using sustainable, collaborative, and cost-effective approaches. Systems-integrated interventions offer promise in terms of producing sustainable impacts on service quality and coverage, but can also improve important data quality and information systems at scale.

Methods

This study assesses the preliminary impacts of a first phase, quasi-experimental, QI health systems intervention on maternal and neonatal health outcomes in four pilot districts in Ethiopia. The intervention identified, trained, and coached QI teams to develop and test change ideas to improve service delivery. We use an interrupted time-series approach to evaluate intervention effects over 32-months. Facility-level outcome indicators included: proportion of mothers receiving four antenatal care visits, skilled delivery, syphilis testing, early postnatal care, proportion of low birth weight infants, and measures of quality delivery of childbirth services.

Results

Following the QI health systems intervention, we found a significant increase in the rate of syphilis testing (ß = 2.41, 95% CI = 0.09,4.73). There were also large positive impacts on health worker adherence to safe child birth practices just after birth (ß = 8.22, 95% CI = 5.15, 11.29). However, there were limited detectable impacts on other facility-usage indicators. Findings indicate early promise of systems-integrated QI on the delivery of maternal health services, and increased some service coverage.

Conclusions

This study preliminarily demonstrates the feasibility of complex, low-cost, health-worker driven improvement interventions that can be adapted in similar settings around the world, though extended follow up time may be required to detect impacts on service coverage. Policy makers and health system workers should carefully consider what these findings mean for scaling QI approaches in Ethiopia and other similar settings.
Caffeine prevents hyperoxia-induced lung injury in neonatal mice through NLRP3 inflammasome and NF-κB pathway
Authors: Chen Shangqin , Wu Qiuping , Zhong Dingjuan , Li Changchong , Du Lizhong
Published: June 2020

Background

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants and hyperoxia exposure is a major cause. In hyperoxic lung injury animal model, alveolar simplification and pro-inflammatory cells infiltration are the main pathophysiologic changes. Caffeine is a drug used to treat apnea in premature infants. Early use of caffeine can decrease the rate and the severity of BPD while the mechanisms are still unclear. The purpose of this study was to evaluate the effects of caffeine on inflammation and lung development in neonatal mice with hyperoxic lung injury and to explore the possible mechanism.

Methods

Following 14 d of 75% oxygen exposure in newborn mouse, the BPD model was established. Caffeine at a dose of 1 g/L was added in drinking water to nursing mouse. We measured the concentration of caffeine in serum and oxidative stress in lung by commercially available kits. Adenosine 2A receptor (A2AR) expression and lung inflammation were measured by Immunohistochemistry and western blotting. Apoptosis and surfactant protein-C (SFTPC) levels were measured by immunofluorescence. The inflammasome and NF-κB pathway proteins were assessed by western blotting.

Results

We found that the caffeine concentration in plasma at present dose significantly decreased the expression of A2AR protein in mice lung. Caffeine treatment significantly reduced oxidative stress, improved weight gain, promoted alveolar development, attenuated inflammatory infiltration and lung injury in hyperoxia-induced lung injury mice. Moreover, caffeine decreased the cell apoptosis in lung tissues, especially the Type II alveolar epithelial cell. The expression of NLRP3 inflammasome protein and NF-κB pathway were significantly inhibited by caffeine treatment.

Conclusion

Caffeine treatment can protect hyperoxia-induced mice lung from oxidative injury by inhibiting NLRP3 inflammasome and NF-κB pathway.
Health care trajectories and barriers to treatment for patients with end-stage renal disease without health insurance in Mexico: a mixed methods approach
Authors: Agudelo-Botero Marcela , González-Robledo María Cecilia , Reyes-Morales Hortensia , Giraldo-Rodríguez Liliana , Rojas-Russell Mario , Mino-León Dolores , Ocampo-Morales Dayan Irene , Valdez-Ortiz Rafael
Published: June 2020

Background

Mexico has the sixth-highest premature death rate from chronic kidney disease (CKD) in the world. From 1990 to 2017, the age-standardized CKD mortality rate jumped from 28.7 to 58.1 per 100,000 inhabitants, making it the second-leading cause of death that year. Medical care for the disease is inequitable, as those without health insurance have limited access to renal replacement therapy (RRT). The objective of this study is to describe the healthcare trajectories of patients with end-stage renal disease (ESRD) in a public hospital in Mexico City and the barriers they face in receiving peritoneal dialysis and haemodialysis.

Methods

This study uses a convergent mixed methods approach and is predominantly qualitative. Patients completed 199 surveys, and 42 semi-structured interviews with patients having ESRD and their families were conducted. The quantitative data were analysed using descriptive statistics, and the qualitative data were processed using a phenomenological approach.

Results

It was found that 76.9% of the patients received peritoneal dialysis or haemodialysis as their first RRT. Over 30% began their treatment at least a month after a health professional prescribed it. Almost 50% had been hospitalized for complications related to the disease in the previous year, and 36% had uncertainties about their treatment. Close to 64% of the haemodialysis patients received treatment intermittently. Barriers to accessing treatment, information, contact with health services, and treatment availability were identified. Patients and their families encountered economic and emotional difficulties at every phase of their search for medical care and treatment.

Conclusion

Mexico urgently needs to implement public policies related to CKD that are primarily directed at its prevention but should also implement policies directed at slowing its progression, reducing its complications, and providing funding for uninsured patients who require RRT. These policies must be based on the perspectives of human rights and equality, and the perspectives of patients, their families and the general population should be included in the policy creation process.
Perceptions of barriers and levers of health-enhancing physical activity policies in mid-size French municipalities
Authors: Noël Racine A. , Garbarino J. M. , Corrion K. , D’Arripe-Longueville F. , Massiera B. , Vuillemin A.
Published: June 2020

Background

Policy is one of the levers for initiating structural change to foster the promotion of health-enhancing physical activity (HEPA). To this end, policy-makers have to deal with complex ecosystems embedded in specific contexts. However, limited research has been conducted on this topic at the local level. The purpose of this study was to identify the perceived barriers and levers of HEPA policies according to department heads and elected officials across various sectors in mid-size French municipalities.

Methods

This study used a mixed method primarily based on an adaptation of the concept mapping approach. A list of statements completing the sentence: ‘In a mid-size municipal context, to develop HEPA policies, it is necessary to …’ was submitted to key informants of 17 mid-sized French cities. Key informants in each municipality first rated the importance of each statement without considering their local context; they then rated the feasibility of each statement given their local context. In both cases, they used a Likert scale ranging from 1 to 6.

Results

A total of 23 municipal department heads and 10 elected officials from the sport (n= 14), health (n= 10) and social (n =9) sectors in 11 mid-size French cities participated in this study. A list of 84 statements, sorted into 16 categories, was rated by participants according to their importance (M =4.52,SD =0.86) and their feasibility (M =3.77,SD =0.74). Potential barriers to (n =10) and levers of (n =38) HEPA policy development were identified. These results varied according to the position and sector of the participants.

Conclusions

The results suggest that local contextual factors can affect the development of HEPA policies in mid-size French municipalities. The different perceptions of the potential levers and barriers according to sector might affect intersectoral collaboration. This study contributes by enhancing understanding of how local HEPA policies are developed in the French context.
Differences in immune-related gene expressions and tumor-infiltrating lymphocytes according to chemotherapeutic response in ovarian high-grade serous carcinoma
Authors: Choi Kyung Un , Kim Ahrong , Kim Jee Yeon , Kim Ki Hyung , Hwang Chungsu , Lee So Jung , Park Won Young , Jung Sejin , Choi Hye Jeong , Kim Kyungbin
Published: June 2020

Background

High-grade serous carcinoma (HGSC) of the ovary is the most common subtype of epithelial ovarian cancer (EOC) and has an overall poor prognosis. There is increasing awareness of the importance of immune cell populations and tumor-infiltrating lymphocytes (TILs) in various immune pathways in the tumor microenvironment. The present study evaluated immune-related gene expressions and TIL levels, as well as associated chemotherapeutic responses, to elucidate the correlation between gene expression and TIL levels in HGSC.

Materials and methods

Fresh tissue samples from 12 HGSC patients were included in this study. Depending on their response to adjuvant chemotherapy, the patients were divided into two groups: chemosensitive (CS) or chemoresistant (CR). The expression levels of 770 genes were analyzed using the nCounter® PanCancer Immune Profiling Panel of the NanoString nCounter® Analysis System. Quantitative real-time polymerase chain reaction (qPCR) was performed to validate the NanoString data obtained. The TIL levels in representative sections were examined via hematoxylin and eosin staining. Gene and TIL levels were subsequently correlated with the chemotherapeutic response.

Results

Several genes were differentially expressed in the two study groups. Eleven representative genes were selected for further evaluation. Of those, 9 genes (IRF1, CXCL9, LTB, CCL5, IL-8, GZMA, PSMB9, CD38, and VCAM1) were significantly overexpressed in the CS group; whereas expressions of 2 genes (CD24 and CD164) were increased in the CR group. Results of qPCR were consistent with those of the NanoString nCounter® analysis. Stromal TIL levels were significantly associated with adjuvant chemotherapeutic response (p = 0.001).

Conclusions

Significant differences between the CS and CR groups were observed in the expression levels of immune-related genes. Immune-related gene expressions were significantly higher in the CS group, which also had higher levels of TILs. We, therefore, suggest that, in patients with HGSC, immune-related gene expressions and TIL levels may be associated with chemotherapeutic sensitivity.
Multiple cross displacement amplification-a more applicable technique in detecting Pseudomonas aeruginosa of ventilator-associated pneumonia (VAP)
Authors: Wang Juxiang , Chen Huimin , Lin Xiaomin , Ji Chengyi , Chen Bin
Published: June 2020

Background

Early and rapid identification of Pseudomonas aeruginosa (P. aeruginosa) in patients with suspected ventilator-associated pneumonia (VAP) provides theoretical clinical advantages in therapeutic optimization strategies.

Methods

The P. aeruginosa-multiple cross displacement amplification (PA-MCDA) assay was conducted at an isothermal temperature during the amplification stage, and products were visually detected by color changes. The entire process was completed within 1 h. A total of 77 strains, including P. aeruginosa species and various other species of non-P. aeruginosa, were used to evaluate PA-MCDA assays. Bronchoalveolar lavage fluid (BALF) of suspected VAP patients was examined by the MCDA assay.

Results

The MCDA assay exhibited a 100% analytical specificity in detecting PA from all 77 strains, and the limit of detection was as low as 100 fg DNA per reaction. A temperature of 65 °C was recommended as standard during the amplification stage. The agreement between PA-MCDA and bacteria culture was 91.18% (κ = 0.787; p = 0.000) in the identification of P. aeruginosa in BALF from suspected VAP. The PA-MCDA assay showed values of 92.31%, 90.78%, 77.41%, and 97.18% for sensitivity, specificity, positive predictive value, and negative predictive value, respectively. PA-MCDA had a higher detective rate of P. aeruginosa than bacteria culture in patients with antipseudomonal therapy.

Conclusions

The instrument-free platform of the MCDA assay makes it a simple, rapid, and applicable procedure for “on-site” diagnosis and point-of-care testing for the presence of P. aeruginosa without the need for specific bacterial culture.
Direct-seq: programmed gRNA scaffold for streamlined scRNA-seq in CRISPR screen
Authors: Song Qingkai , Ni Ke , Liu Min , Li Yini , Wang Lixia , Wang Yingying , Liu Yingzheng , Yu Zhenxing , Qi Yinyao , Lu Zhike , Ma Lijia
Published: June 2020

CRISPR-based genome perturbation provides a new avenue to conveniently change DNA sequences, transcription, and epigenetic modifications in genetic screens. However, it remains challenging to assay the complex molecular readouts after perturbation at high resolution and at scale. By introducing an A/G mixed capture sequence into the gRNA scaffold, we demonstrate that gRNA transcripts could be directly reverse transcribed by poly (dT) primer together with the endogenous mRNA, followed by high-content molecular phenotyping in scRNA-seq (Direct-seq). With this method, the CRISPR perturbation and its transcriptional readouts can be profiled together in a streamlined workflow.
An update on the incidence of human giardiasis in Scotland, 2011–2018
Authors: Ferguson Lynne C. , Smith-Palmer Alison , Alexander Claire L.
Published: June 2020

Background

Giardia duodenalis is one of the most common parasites in the UK to cause diarrhoeal illness. Giardiasis is likely to be significantly under-reported in the UK as laboratory testing is largely based on examining stool samples from individuals with a recent travel history. This results in the majority of locally-acquired cases going undetected. To increase awareness of giardiasis, we describe data gathered from cases reported within Scotland during 2011–2018.

Methods

All of the 21 Scottish National Health Service (NHS) diagnostic microbiology laboratories performed microscopy examination to detect Giardia cysts in stools, from mostly travel-related cases. The exception was one laboratory that implemented an antigen-based enzyme immunoassay in 2015. This resulted in every submitted stool being tested for Giardia. Laboratory-confirmed cases of giardiasis were reported to Health Protection Scotland (HPS) via the Electronic Communication of Surveillance in Scotland (ECOSS) during the eight-year period. Data for calculating the incidence per 100,000 of the population were obtained from the National Records of Scotland mid-2018 population estimates in Scotland.

Results

A total of 1631 Scottish cases were reported during 2011–2018 (8-year mean: 204; range: 166–269). National Health Service Grampian, Borders and Lothian reported the highest incidence of Giardia (9.8, 7.5 and 6.7 per 100,000, respectively), all of which were above the Scottish mean incidence (3.8 per 100,000). Following the implementation of antigen testing in NHS Grampian during 2015, reports significantly increased 3.6-fold (P = 0.005). The highest incidence of giardiasis occurred in the 20–49 years age group (mean 5.4 per 100,000). Of interest, the mean incidence of giardiasis was significantly higher in males than in females (4.8 versus 3.1 per 100,000, respectively; P < 0.0001).

Conclusions

This report highlights the need to capture enhanced information on every laboratory-confirmed case of giardiasis to gain a better understanding of the local sources and transmission pathways occurring in Scotland. In addition, implementing sensitive, automated technologies across UK NHS diagnostic microbiology laboratories to permit the efficient, routine testing of every submitted stool for Giardia, should be encouraged to ensure all cases are identified and treated appropriately.
Nutrition as an etiological factor causing diseases in endangered huemul deer
Authors: Flueck Werner T.
Published: June 2020

Objectives

Distinct diseases prevent endangered huemul deer (Hippocamelus bisulcus) recovery. Fundamental etiological factors include nutriments, a mayor component of habitat quality. Undernutrition affects growth, skeletal development, osteopathology, reproduction and immunocompetence: this paper amplifies data corroborating micro-nutrient deficiencies among huemul.

Results

In Argentina, 57% huemul cadavers exhibited osteopathology, with new cases reported here. Recently, 86% live huemul had osteopathology: cranial lesions involved antemortem tooth loss, reducing feeding efficiency and body condition, with starvation deaths. This population had tissues well deficient compared to other cervids, averaging 0.28 ppm selenium, 4.98 ppm copper, whereas for manganese 55% were deficient (2.52 ppm) and 45% adequate (42.79 ppm). Recently, lesions in one Chilean huemul were interpreted to stem from parapoxvirus. That population also has cases with cranial osteopathologies, high disease susceptibility (parapoxvirus, parasitism, foot lesions), crippled antlers, and low density, indicative of marginal habitat and primary etiological factors like undernutrition and immunosuppression. The reported atypical symptoms attributed to parapoxvirus may relate to probable diagnostic limitations, but does support presence of nutritional deficiencies. Patagonia has selenium deficient plants and livestock, including severe muscular dystrophy, and soil levels in extant huemul areas considered very deficient. Moreover, 73% of Chilean huemul were selenium deficient and 64% severely deficient with concomitant cranial osteopathology.
The signature of HBV-related liver disease in peripheral blood mononuclear cell DNA methylation
Authors: Li Kang , Qin Ling , Jiang Sanjie , Li Ang , Zhang Chi , Liu Guihai , Sun Jianping , Sun Huanqing , Zhao Yan , Li Ning , Zhang Yonghong
Published: June 2020

Background

Hepatitis B virus (HBV)-related liver disease induces liver damage by hepatic immune and inflammatory response. The association between aberrant peripheral blood mononuclear cell (PBMC) DNA methylation and progression of liver disease and fibrosis remains unclear.

Results

Here we applied Infinium 450 K BeadChip investigating PBMC genome-wide methylation profiling of 48 HBV-related liver disease patients including 24 chronic hepatitis B (CHB), 14 compensated liver cirrhosis (LC), and 10 decompensated liver cirrhosis (DLC). In total, there were 7888 differentially methylated CpG sites (36.06% hypermethylation, 63.94% hypomethylation) correlate with liver disease progression. LC was difficult to be diagnosed, intermediating between CHB and DLC. We used least absolute shrinkage and selection operator (LASSO)-logistic regression method to perform a LC predictive model. The predicted probability (P) of having LC was estimated by the combined model: P = 1/(1 − e−x), where X = 11.52 − 2.82 × (if AST within the normal range − 0.19 × (percent methylation of cg05650055) − 0.21 × (percent methylation of cg17149911 ). Pyrosequencing validation and confusion matrix analysis was used for internal testing, area under receiver operating characteristic curve (AUROC) of model was 0.917 (95% CI, 0.80–0.977). On the fibrosis progress, there were 1705 genes in LC compared with CHB, whose differentially methylated CpG sites loading within the “promoter” regions (including TSS1500, TSS200, 5′UTR, and the 1st exon of genes) subject into the enrichment analysis using Ingenuity Pathway Analysis (IPA). There were 113 enriched immune-related pathways indicated that HBV-related liver fibrosis progression caused epigenetic reprogramming of the immune and inflammatory response.

Conclusions

These data support idea that development of HBV-related chronic liver disease is linked with robust and broad alteration of methylation in peripheral immune system. CpG methylation sites serve as relevant biomarker candidates to monitor and diagnose LC, providing new insight into the immune mechanisms understanding the progression of HBV-related liver fibrosis and cirrhosis.
Exosomes derived from mesenchymal stem cells inhibit neointimal hyperplasia by activating the Erk1/2 signalling pathway in rats
Authors: Liu Zhihui , Wu Chao , Zou Xinliang , Shen Weiming , Yang Jiacai , Zhang Xiaorong , Hu Xiaohong , Wang Haidong , Liao Yi , Jing Tao
Published: June 2020

Background

Restenosis is a serious problem in patients who have undergone percutaneous transluminal angioplasty. Endothelial injury resulting from surgery can lead to endothelial dysfunction and neointimal formation by inducing aberrant proliferation and migration of vascular smooth muscle cells. Exosomes secreted by mesenchymal stem cells have been a hot topic in cardioprotective research. However, to date, exosomes derived from mesenchymal stem cells (MSC-Exo) have rarely been reported in association with restenosis after artery injury. The aim of this study was to investigate whether MSC-Exo inhibit neointimal hyperplasia in a rat model of carotid artery balloon-induced injury and, if so, to explore the underlying mechanisms.

Methods

Characterization of MSC-Exo immunophenotypes was performed by electron microscopy, nanoparticle tracking analysis and western blot assays. To investigate whether MSC-Exo inhibited neointimal hyperplasia, rats were intravenously injected with normal saline or MSC-Exo after carotid artery balloon-induced injury. Haematoxylin-eosin staining was performed to examine the intimal and media areas. Evans blue dye staining was performed to examine re-endothelialization. Moreover, immunohistochemistry and immunofluorescence were performed to examine the expression of CD31, vWF and α-SMA. To further investigate the involvement of MSC-Exo-induced re-endothelialization, the underlying mechanisms were studied by cell counting kit-8, cell scratch, immunofluorescence and western blot assays.

Results

Our data showed that MSC-Exo were ingested by endothelial cells and that systemic injection of MSC-Exo suppressed neointimal hyperplasia after artery injury. The Evans blue staining results showed that MSC-Exo could accelerate re-endothelialization compared to the saline group. The immunofluorescence and immunohistochemistry results showed that MSC-Exo upregulated the expression of CD31 and vWF but downregulated the expression of α-SMA. Furthermore, MSC-Exo mechanistically facilitated proliferation and migration by activating the Erk1/2 signalling pathway. The western blot results showed that MSC-Exo upregulated the expression of PCNA, Cyclin D1, Vimentin, MMP2 and MMP9 compared to that in the control group. Interestingly, an Erk1/2 inhibitor reversed the expression of the above proteins.

Conclusion

Our data suggest that MSC-Exo can inhibit neointimal hyperplasia after carotid artery injury by accelerating re-endothelialization, which is accompanied by activation of the Erk1/2 signalling pathway. Importantly, our study provides a novel cell-free approach for the treatment of restenosis diseases after intervention.
Bone marrow mesenchymal stem cell-derived endothelial cells increase capillary density and accelerate angiogenesis in mouse hindlimb ischemia model
Authors: Yao Ziping , Liu Huihui , Yang Min , Bai Yun , Zhang Bihui , Wang Chengen , Yan Ziguang , Niu Guochen , Zou Yinghua , Li Yuan
Published: June 2020

Background

Mesenchymal stem cells (MSCs) can improve limb perfusion and increase vessel density in a murine model of hindlimb ischemia. But low engraftment rate of those cells limited their therapeutic effect. Endothelial cells (ECs) play an important role in neovascularization. And MSCs can differentiate into ECs in vitro. The aim of this study is to investigate if EC differentiation of MSCs in vitro before transplantation is effective in improving therapeutic outcomes in the treatment of ischemic disease in a murine ischemia animal model.

Methods

MSCs were isolated from the bone marrow of EGFP-transgenic mice by density gradient centrifugation. The identity of the MSCs was determined by their cluster of differentiation (CD) marker profile by flow cytometry. Inducing medium containing a few cytokines was applied to induce the MSCs to differentiate into ECs. Endothelial differentiation was quantitatively evaluated using flow cytometry, quantitative real-time PCR (qRT-PCR), immunofluorescence, Matrigel tube formation assay, and Dil-labeled acetylated low-density lipoprotein uptake assay. Mouse hindlimb ischemia model was made by excision of the femoral artery. Uninduced EGFP+ MSCs, induced EGFP+ MSCs, and PBS were intramuscularly injected into the gastrocnemius following ischemia no later than 24 h after operation. Restoration of blood flow and muscle function was evaluated by laser Doppler perfusion imaging. Immunofluorescence was conducted to evaluate the engraftment of transplanted MSCs. Histological analysis was performed to evaluate blood vessel formation.

Results

Induced EGFP+ MSCs expressed endothelial markers and exhibited tube formation capacity. Mice in the induced EGFP+ MSCs group had a better blood perfusion recovery, enhanced vessel densities, higher engraftment, and improved function of the ischemic limb than those in the uninduced EGFP+ MSCs or PBS groups.

Conclusions

This study reveals that after short-term pre-treatment in the EC-inducing medium, induced MSCs acquire stronger vessel formation capability and enhanced angiogenic therapeutic effect in the murine hindlimb ischemia model.
Plasma membrane vesicles of human umbilical cord mesenchymal stem cells ameliorate acetaminophen-induced damage in HepG2 cells: a novel stem cell therapy
Authors: Lin Mei-jia , Li Shuang , Yang Lu-jun , Ye Dan-yan , Xu Li-qun , Zhang Xin , Sun Ping-nan , Wei Chi-ju
Published: June 2020

Background

Acetaminophen (APAP) overdose is the common cause of acute liver failure (ALF) due to the oxidative damage of multiple cellular components. This study aimed to investigate whether plasma membrane vesicles (PMVs) from human umbilical cord mesenchymal stem cells (hUCMSCs) could be exploited as a novel stem cell therapy for APAP-induced liver injury.

Methods

PMVs from hUCMSCs were prepared with an improved procedure including a chemical enucleation step followed by a mechanical extrusion. PMVs of hUCMSCs were characterized and supplemented to hepatocyte cultures. Rescue of APAP-induced hepatocyte damage was evaluated.

Results

The hUCMSCs displayed typical fibroblastic morphology and multipotency when cultivated under adipogenic, osteogenic, or chondrogenic conditions. PMVs of hUCMSCs maintained the stem cell phenotype, including the presence of CD13, CD29, CD44, CD73, and HLA-ABC, but the absence of CD45, CD117, CD31, CD34, and HLA-DR on the plasma membrane surface. RT-PCR and transcriptomic analyses showed that PMVs were similar to hUCMSCs in terms of mRNA profile, including the expression of stemness genes GATA4/5/6, Nanog, and Oct1/2/4. GO term analysis showed that the most prominent reduced transcripts in PMVs belong to integral membrane components, extracellular vesicular exosome, and extracellular matrix. Immunofluorescence labeling/staining and confocal microscopy assays showed that PMVs enclosed cellular organelles, including mitochondria, lysosomes, proteasomes, and endoplasmic reticula. Incorporation of the fusogenic VSV-G viral membrane glycoprotein stimulated the endosomal release of PMV contents into the cytoplasm. Further, the addition of PMVs and a mitochondrial-targeted antioxidant Mito-Tempo into cultures of APAP-treated HepG2 cells resulted in reduced cell death, enhanced viability, and increased mitochondrial membrane potential. Lastly, this study demonstrated that the redox state and activities of aminotransferases were restored in APAP-treated HepG2 cells.

Conclusions

The results suggest that PMVs from hUCMSCs could be used as a novel stem cell therapy for the treatment of APAP-induced liver injury.
Regional SUV quantification in hybrid PET/MR, a comparison of two atlas-based automatic brain segmentation methods
Authors: Ruan Weiwei , Sun Xun , Hu Xuehan , Liu Fang , Hu Fan , Guo Jinxia , Zhang Yongxue , Lan Xiaoli
Published: June 2020

Background

Quantitative analysis of brain positron-emission tomography (PET) depends on structural segmentation, which can be time-consuming and operator-dependent when performed manually. Previous automatic segmentation usually registered subjects’ images onto an atlas template (defined as RSIAT here) for group analysis, which changed the individuals’ images and probably affected regional PET segmentation. In contrast, we could register atlas template to subjects’ images (RATSI), which created an individual atlas template and may be more accurate for PET segmentation. We segmented two representative brain areas in twenty Parkinson disease (PD) and eight multiple system atrophy (MSA) patients performed in hybrid positron-emission tomography/magnetic resonance imaging (PET/MR). The segmentation accuracy was evaluated using the Dice coefficient (DC) and Hausdorff distance (HD), and the standardized uptake value (SUV) measurements of these two automatic segmentation methods were compared, using manual segmentation as a reference.

Results

The DC of RATSI increased, and the HD decreased significantly (P < 0.05) compared with the RSIAT in PD, while the results of one-way analysis of variance (ANOVA) found no significant differences in the SUVmean and SUVmax among the two automatic and the manual segmentation methods. Further, RATSI was used to compare regional differences in cerebral metabolism pattern between PD and MSA patients. The SUVmean in the segmented cerebellar gray matter for the MSA group was significantly lower compared with the PD group (P < 0.05), which is consistent with previous reports.

Conclusion

The RATSI was more accurate for the caudate nucleus and putamen automatic segmentation and can be used for regional PET analysis in hybrid PET/MR.
KLF13 suppresses the proliferation and growth of colorectal cancer cells through transcriptionally inhibiting HMGCS1-mediated cholesterol biosynthesis
Authors: Yao Weilong , Jiao Yue , Zhou Yanhua , Luo Xiaoya
Published: June 2020

Background

Colorectal cancer (CRC) is the fourth most deadly malignancy throughout the world. Extensive studies have shown that Krüppel-like factors (KLFs) play essential roles in cancer development. However, the function of KLF13 in CRC is unclear.

Methods

The Cancer Genome Atlas database was applied to analyze the expression of KLF13 in CRC and normal tissues. Lentivirus system was used to overexpress and to knock down KLF13. RT-qPCR and Western blot assays were performed to detect mRNA and protein expression. CCK-8, colony formation, cell cycle analysis and EdU staining were used to assess the in vitro function of KLF13 in CRC cells. Xenografter tumor growth was used to evaluate the in vivo effect of KLF13 in CRC. Cholesterol content was measured by indicated kit. Transcription activity was analyzed by luciferase activity measurement. ChIP-qPCR assay was performed to assess the interaction of KLF13 to HMGCS1 promoter.

Results

KLF13 was downregulated in CRC tissues based on the TCGA database and our RT-qPCR and Western blot results. Comparing with normal colorectal cells NCM460, the CRC cells HT-26, HCT116 and SW480 had reduced KLF13 expression. Functional experiments showed that KLF13 knockdown enhanced the proliferation and colony formation in HT-29 and HCT116 cells. Opposite results were observed in KLF13 overexpressed cells. Furthermore, KLF13 overexpression resulted in cell cycle arrest at G0/G1 phase, reduced EdU incorporation and suppressed tumor growth of HCT116 cells in nude mice. Mechanistically, KLF13 transcriptionally inhibited HMGCS1 and the cholesterol biosynthesis. Knockdown of HMGCS1 suppressed cholesterol biosynthesis and the proliferation of CRC cells with silenced KLF13. Furthermore, cholesterol biosynthesis inhibitor significantly retarded the colony growth in both cells.

Conclusions

Our study reveals that KLF13 acts as a tumor suppressor in CRC through negatively regulating HMGCS1-mediated cholesterol biosynthesis.
The effects of park-based interventions on health: a systematic review protocol
Authors: Wallace Deshira D. , Derose Kathryn P. , Han Bing , Cohen Deborah A.
Published: June 2020

Background

Public parks serve as spaces within neighborhoods for encouraging a variety of physical and mental health-related behaviors. Over the past decade, there have been a number of interventions conducted in public parks, often aimed at improving an aspect of mental or physical health. A common type of park-based interventions is aimed at increasing physical activity among adults and children.

Methods

We will conduct a systematic review of peer-reviewed articles on the effects of park-based interventions on physical and mental health outcomes of adults and youth (children and adolescents). An electronic search will be conducted in four electronic databases: Web of Science, PubMed/MEDLINE, Cochrane Library, and Scopus. Manual hand-searching of reference lists from studies identified as relevant by experts and of systematic reviews resulting from the search strategy will be conducted to further identify articles of interest. Inclusion criteria are peer-reviewed, quantitative studies, studies detailing an intervention conducted in a park setting, which was at the person-level or place-level, and studies published in English or Spanish. A three-stage approach will be used to screen title and abstracts and full-text articles against the inclusion and exclusion criteria and, lastly, extract data from eligible studies. Study quality will be assessed by the Cochrane Risk of Bias and the Community Guide’s Guide to Community Preventive Services tools. Extracted data will be summarized narratively and meta-analysis will be conducted, if appropriate.

Discussion

We aim to find relevant studies proving evidence for park-based intervention studies and their effects on health-related outcomes for youth and adults. The evidence obtained from the included studies will help guide future studies on park-based interventions. The study results will be submitted to a peer-reviewed journal for electronic dissemination.

Systematic review registration

Systematic review registration: PROSPERO CRD42018109165.