bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the efficacy of two doses of vitamin D supplementation on glycemic, lipidemic and oxidative stress biomarkers during pregnancy: a randomized clinical trial
Authors: Motamed Soudabe , Nikooyeh Bahareh , Kashanian Maryam , Chamani Maryam , Hollis Bruce W. , Neyestani Tirang R.
Published: October 2020

Background

Vitamin D deficiency during pregnancy is common and is likely to be associated with metabolic complications in the mother. The aim of this study was to assess the efficacy of two doses of vitamin D supplementation during pregnancy on maternal and cord blood vitamin D status and metabolic and oxidative stress biomarkers.

Methods

The eligible pregnant women (n = 84) invited to participate in the study and randomly allocated to one of the two supplementation groups (1000 IU/d vitamin D and 2000 IU/d).

Biochemical assessments of mothers including serum concentrations of 25(OH)D, calcium, phosphate, iPTH, fasting serum sugar (FBS), insulin, triglyceride, total cholesterol, LDL-C, HDL-C, malondialdehyde (MDA) and total antioxidant capacity (TAC) were done at the beginning and 34 weeks of gestation. Cord blood serum concentrations of 25(OH)D, iPTH, MDA and TAC were assessed at delivery as well. To determine the effects of vitamin D supplementation on metabolic markers 1-factor repeated-measures analysis of variance (ANOVA) was used. Between groups comparisons was done by using Independent-samples Student’st-test or Mann-Whitney test.P < 0.05 was considered as significant.

Results

Supplementation with 1000 IU/d and 2000 IU/d vitamin D resulted in significant changes in vitamin D status over pregnancy (24.01 ± 21.7,P < 0.001 in 1000 IU/d group and 46.7 ± 30.6 nmol/L,P < 0.001 in 2000 IU/d group). Daily intake of 2000 compared with 1000 IU/d tended to increase the serum concentration of HDL-C (10 ± 8.37,P < 0.001 in 1000 IU/d group and 9.52 ± 11.39 mg/dL,P < 0.001 in 2000 IU/d group). A significant decrement in serum concentration of iPTH observed in both groups (− 4.18 ± 7.5,P = 0.002 in 1000 IU/d group and − 8.36 ± 14.17,P = 0.002 in 2000 IU/d group).

Conclusions

Supplementation with 2000 IU/d vitamin D as compared with 1000 IU/d, is more effective in promoting vitamin D status and HDL-C serum concentration and in decreasing iPTH over pregnancy.

Trial registration

This trial is registered atclinicaltrials.gov(NCT03308487). Registered 12 October 2017 ‘retrospectively registered’.
Analyses of the local control of pulmonary Oligometastases after stereotactic body radiotherapy and the impact of local control on survival
Authors: Yamamoto Takaya , Niibe Yuzuru , Aoki Masahiko , Shintani Takashi , Yamada Kazunari , Kobayashi Mitsuru , Yamashita Hideomi , Ozaki Masatoki , Manabe Yoshihiko , Onishi Hiroshi , Yahara Katsuya , Nishikawa Atsushi , Katsui Kuniaki , Oh Ryoong-Jin , Terahara Atsuro , Jingu Keiichi
Published: October 2020

Background

Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicentre retrospective study was to investigate factors affecting the local control (LC) of pulmonary oligometastases treated by stereotactic body radiotherapy (SBRT) and to investigate the impact of LC on survival.

Methods

The inclusion criteria included 1 to 5 metastases, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED10) of the SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses.

Results

Data of 1378 patients with 1547 tumours from 68 institutions were analysed. The median follow-up period was 24.2 months. The one-year, 3-year and 5-year LC rates were 92.1, 81.3 and 78.6%, respectively, and the 1-year, 3-year and 5-year overall survival rates were 90.1, 60.3 and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumour diameter (p = 0.011), type A dose calculation algorithm (p = 0.005), shorter overall treatment time of SBRT (p = 0.035) and colorectal primary origin (p < 0.001 excluding oesophagus origin) were significantly associated with a lower LC rate. In the survival analysis, local failure (p < 0.001), worse performance status (1 vs. 0, p = 0.013; 2–3 vs. 0, p < 0.001), oesophageal primary origin (vs. colorectal origin, p = 0.038), squamous cell carcinoma (vs. adenocarcinoma, p = 0.006) and increased maximum tumour diameter (p < 0.001) showed significant relationships with shorter survival.

Conclusions

Several factors of oligometastases and SBRT affected LC. LC of pulmonary oligometastases by SBRT showed a significant survival benefit compared to patients with local failure.
Cross-sectional study of the anthropometric characteristics of children with congenital Zika syndrome up to 12 months of life
Authors: Carvalho-Sauer Rita de Cássia Oliveira de , Costa Maria da Conceição Nascimento , Paixão Enny S. , de Jesus Silva Natanael , Barreto Florisneide Rodrigues , Teixeira Maria Gloria
Published: October 2020

Background

Little is known about physical development of children with Congenital Zika Syndrome (CZS). This study aims to evaluate the anthropometric characteristics of children with CZS up to 12 months.

Methods

This is a cross-sectional study developed with 46 children with CZS living in Bahia. We used the Public Health Events Register, Live Births Information System and Childcare Records of Primary Health Care Services. Descriptive analysis was performed by distributing absolute and relative frequencies and median and interquartile range. The Weight/Age (W/A), Length/Age (L/A), Weight/Length (W/L) and Head Circumference/Age (HC/A) indexes were calculated for each month and expressed in z-score values, and the results were evaluated individually and by group average. Values between ≥ − 2 and ≤ 2 standard deviations were used as reference. T-Student and Spearman’s Correlation Tests were applied to verify the existence of any relationship between maternal and children’s variables with the anthropometric indexes weight/age and height/age at birth and at 3, 6 and 12 months of age.

Results

The studied children had high proportions of low birth weight (23.9%), dysphagia (56.8%) and seizures (53.5%). The mean z-score for the HC/A index at birth was − 3.20 and remained below − 3 z-scores throughout the assessed period. The analysis of the indices equivalent to every single child’s anthropometric measurement showed a deficit in 20.4% of the W/A, 39.1% of the L/A, 9.2% of the W/L and 85.7% of the HC/A measurements. Distribution of the mean values of these anthropometric indices revealed a risk of delayed stature growth (L/A < -1 z-score). There was a statistically significant association between L/A at 12 months and dysphagia (p = 0.0148) and a positive correlation between breastfeeding time and W/A. No statistically significant correlation was found between any other tested variables.

Conclusions

We observed a deficit in the HC/A index, which is a common feature in CZS, but also a high proportion of W/A and L/A deficit. The average group z-score highlighted the risk of delay in stature growth for age, which calls attention to the need for health interventions, as this condition exposes them to a higher risk of morbidity and mortality.
Study protocol of comprehensive risk evaluation for anorexia nervosa in twins (CREAT): a study of discordant monozygotic twins with anorexia nervosa
Authors: Seidel Maria , Ehrlich Stefan , Breithaupt Lauren , Welch Elisabeth , Wiklund Camilla , Hübel Christopher , Thornton Laura M. , Savva Androula , Fundin Bengt T. , Pege Jessica , Billger Annelie , Abbaspour Afrouz , Schaefer Martin , Boehm Ilka , Zvrskovec Johan , Rosager Emilie Vangsgaard , Hasselbalch Katharina Collin , Leppä Virpi , Sjögren Magnus , Nergårdh Ricard , Feusner Jamie D. , Ghaderi Ata , Bulik Cynthia M.
Published: October 2020

Background

Anorexia nervosa (AN) is a severe disorder, for which genetic evidence suggests psychiatric as well as metabolic origins. AN has high somatic and psychiatric comorbidities, broad impact on quality of life, and elevated mortality. Risk factor studies of AN have focused on differences between acutely ill and recovered individuals. Such comparisons often yield ambiguous conclusions, as alterations could reflect different effects depending on the comparison. Whereas differences found in acutely ill patients could reflect state effects that are due to acute starvation or acute disease-specific factors, they could also reflect underlying traits. Observations in recovered individuals could reflect either an underlying trait or a “scar” due to lasting effects of sustained undernutrition and illness. The co-twin control design (i.e., monozygotic [MZ] twins who are discordant for AN and MZ concordant control twin pairs) affords at least partial disambiguation of these effects.

Methods

Comprehensive Risk Evaluation for Anorexia nervosa in Twins (CREAT) will be the largest and most comprehensive investigation of twins who are discordant for AN to date. CREAT utilizes a co-twin control design that includes endocrinological, neurocognitive, neuroimaging, genomic, and multi-omic approaches coupled with an experimental component that explores the impact of an overnight fast on most measured parameters.

Discussion

The multimodal longitudinal twin assessment of the CREAT study will help to disambiguate state, trait, and “scar” effects, and thereby enable a deeper understanding of the contribution of genetics, epigenetics, cognitive functions, brain structure and function, metabolism, endocrinology, microbiology, and immunology to the etiology and maintenance of AN.
A case report of idiopathic pleuroparenchymal fibroelastosis with severe respiratory failure in pregnancy
Authors: Sekine Aiko , Seo Kohei , Matsukura Satoshi , Sato Masaaki , Shinozaki-Ushiku Aya , Ogura Takashi , Kitami Akihiko , Kadokura Mitsutaka , Dohi Satoshi , Ichizuka Kiyotake , Nagatsuka Masaaki
Published: October 2020

Background

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare lung disease that manifests as parenchymal fibrosis of the upper lung lobe and pleura. There have been no reports of IPPFE complicating pregnancy. Here, we report a case of IPPFE that deteriorated rapidly during pregnancy.

Case presentation

A 29-year-old woman presented with dyspnea and dry cough at 19 weeks of gestation. IPPFE with acute exacerbation was suspected on chest computed tomography (CT). Despite steroid treatment, her condition progressed. A cesarean section was performed at 28 weeks of gestation. On postoperative day 26, she underwent living-donor lung transplantation. She was discharged a year after transplantation.

Conclusion

Our experience suggested that when pregnancy is complicated by PPFE, the disease may deteriorate rapidly. In this case, even though IPPFE with acute exacerbation was diagnosed during pregnancy, live birth was achieved, and the mother survived after lung transplantation. Lung transplantation should be considered in these patients because, once advanced, pulmonary lesions may be irreversible.
Beliefs, attitude, and knowledge of the Iranian physiatrists towards neuromusculoskeletal ultrasound and common barriers in its application
Authors: Khodadadi Leyla , Karimzade Afshin , Rayegani Seyed Mansoor , Jafarian Nafisseh , Raeissadat Seyed Ahmad , Yasrebi Sina , Babaei-Ghazani Arash , Eftekharsadat Bina
Published: October 2020

Background

Regarding the increasing application of neuromusculoskeletal sonography among medical specialties, specifically physiatrists, this study aims to assess the knowledge and skill level of these specialists in neuromusculoskeletal sonography in Iran.

Methods

This descriptive, cross-sectional study was performed in 2018. The utilized questionnaire developed based on previous studies in collaboration with 6 university lecturers of Shaheed Beheshti, Iran, and Tabriz medical universities and a physiatrist from Hacettepe University (Turkey); it included questions entailing demographic data, knowledge, and performance levels. Its validity and reliability were evaluated through face validation, pilot study, and the Cronbach α calculated via SPSS. Data extraction and analysis were also performed by SPSS-25.

Results

Of 364 questionnaires distributed, 300 were properly filled and entered into the study, of which, 38% were filled by clinical residents, 10% university lecturers, and 52% other categories (e.g. private sector).

The average number of musculoskeletal patient visits was 140.6 ± 119 and the mean number of musculoskeletal sonographies requested was 8.2 ± 5.2 per month (the three most common indications reported as the shoulder, carpal tunnel syndrome, and tendon injuries).

95% of the participants considered the importance of sonography for physiatrists to be “very high” or “high”; with the most valuable applications “as a guide for procedures (90%), its diagnostic utility (68%), and follow up/evaluating the response to treatment (45%). 86% of physiatrists reported they had participated in musculoskeletal sonography courses, 60% during residency, and the rest through workshops.

Also, the participants mentioned safety (83%), the possibility of performing simultaneous diagnosis and intervention procedures (70%), repeatability (58%), and dynamic imagery (52%) as the major advantages of musculoskeletal ultrasound.

Conclusion

a large number of doctors consider musculoskeletal sonography to be essential for physiatrists, though insufficient education on the subject and the low number of ultrasound devices are some of the obstacles in enhancing the use of this technology in PM&R setting. Presenting certified specific training courses during residency, provision of necessary rotations, using the capacities of the PM&R scientific committee, and the private sector for running workshops and professional training courses are suggested for enhancing the knowledge and skills of neuromusculoskeletal sonography.
Association of surgical approach and prolonged opioid prescriptions in patients undergoing major pelvic cancer procedures
Authors: Krimphove Marieke J. , Chen Xi , Marchese Maya , Friedlander David F. , Fields Adam C. , Roa Lina , Pucheril Daniel , Kibel Adam S. , Melnitchouk Nelya , Urman Richard D. , Kluth Luis A. , Dasgupta Prokar , Trinh Quoc-Dien
Published: October 2020

Background

The rise in deaths attributed to opioid drugs has become a major public health problem in the United States and in the world. Minimally invasive surgery (MIS) is associated with a faster postoperative recovery and our aim was to investigate if the use of MIS was associated with lower odds of prolonged opioid prescriptions after major procedures.

Methods

Retrospective study using the IBM Watson Health Marketscan® Commerical Claims and Encounters Database investigating opioid-naïve cancer patients aged 18–64 who underwent open versus MIS radical prostatectomy (RP), partial colectomy (PC) or hysterectomy (HYS) from 2012 to 2017. Propensity weighted logistic regression analyses were used to estimate the independent effect of surgical approach on prolonged opioid prescriptions, defined as prescriptions within 91–180 days of surgery.

Results

Overall, 6838 patients underwent RP (MIS 85.5%), 4480 patients underwent PC (MIS 61.6%) and 1620 patients underwent HYS (MIS 41.8%). Approximately 70–80% of all patients had perioperative opioid prescriptions. In the weighted model, patients undergoing MIS were significantly less likely to have prolonged opioid prescriptions in all three surgery types (Odds Ratio [OR] 0.737, 95% Confidence Interval [CI] 0.595–0.914, p = 0.006; OR 0.728, 95% CI 0.600–0.882, p = 0.001; OR 0.655, 95% CI 0.466–0.920, p = 0.015, respectively).

Conclusion

The use of the MIS was associated with lower odds of prolonged opioid prescription in all procedures examined. While additional studies such as clinical trials are needed for further confirmation, our findings need to be considered for patient counseling as postoperative differences between approaches do exist.
Odontoid fractures: impact of age and comorbidities on surgical decision making
Authors: Rizvi Syed Ali Mujtaba , Helseth Eirik , Rønning Pål , Mirzamohammadi Jalal , Harr Marianne Efskind , Brommeland Tor , Aarhus Mads , Høstmælingen Christina Teisner , Ølstørn Håvard , Rydning Pål Nicolay Fougner , Mejlænder-Evjensvold Magnus , Utheim Nils Christian , Linnerud Hege
Published: October 2020

Background

Surgical fixation is recommended for type II and III odontoid fractures (OFx) with major translation of the odontoid fragment, regardless of the patient’s age, and for all type II OFx in patients aged ≥50 years. The level of compliance with this recommendation is unknown, and our hypothesis is that open surgical fixation is less frequently performed than recommended. We suspect that this discrepancy might be due to the older age and comorbidities among patients with OFx.

Methods

We present a prospective observational cohort study of all patients in the southeastern Norwegian population (3.0 million) diagnosed with a traumatic OFx in the period from 2015 to 2018.

Results

Three hundred thirty-six patients with an OFx were diagnosed, resulting in an overall incidence of 2.8/100000 persons/year. The median age of the patients was 80 years, and 45% were females. According to the Anderson and D’Alonzo classification, the OFx were type II in 199 patients (59%) and type III in 137 patients (41%). The primary fracture treatment was rigid collar alone in 79% of patients and open surgical fixation in 21%. In the multivariate analysis, the following parameters were significantly associated with surgery as the primary treatment: independent living, less serious comorbidities prior to the injury, type II OFx and major sagittal translation of the odontoid fragment. Conversion from external immobilization alone to subsequent open surgical fixation was performed in 10% of patients. Significant differences the in conversion rate were not observed between patients with type II and III fractures. The level of compliance with the treatment recommendations for OFx was low. The main deviation was the underuse of primary surgical fixation for type II OFx. The most common reasons listed for choosing primary external immobilization instead of primary surgical fixation were an older age and comorbidities.

Conclusion

Major comorbidities and an older age appear to be significant factors contributing to physicians’ decision to refrain from the surgical fixation of OFx. Hence, comorbidities and age should be considered for inclusion in the decision tree for the choice of treatment for OFx in future guidelines.
Acupuncture for ulcerative colitis: a systematic review and meta-analysis of randomized clinical trials
Authors: Wang Xiao , Zhao Nan-qi , Sun Yu-xin , Bai Xue , Si Jiang-tao , Liu Jian-ping , Liu Zhao-lan
Published: October 2020

Background

Ulcerative colitis, characterized by diarrhea, bloody stools and abdominal pain, is a chronic, idiopathic inflammatory disease of the colonic mucosa. In recent years, the incidence of ulcerative colitis presents an increasing trend year by year. Acupuncture, as a potential effective treatment for ulcerative colitis, is widely used in clinical practice.

Methods

We searched PubMed, the Cochrane Library, Chinese CBM Database, China National Knowledge Infrastructure, Chinese VIP Information, and Wanfang Database from the date of the establishment of each database up to March, 2019. We included randomized controlled clinical trials (RCT) comparing acupuncture versus conventional conventional medicine or comparing acupuncture combined with conventional medicine versus conventional medicine in participants with ulcerative colitis. Two authors screened all references, assessed the risk of bias and extracted data independently. We summarized data using risk ratios (RR) with 95% confidence intervals (CI) for binary outcomes. We performed meta-analyses using random effects model. We assessed overall quality of evidence using GRADE.

Results

We included 13 RCTs (1030 participants, 515 in the acupuncture group and 515 in the control group). Only one study tested head acupuncture, and the other 12 tested body acupuncture. The treatment duration ranged from 14 to 60 days. Seven trials compared acupuncture alone versus conventional medicine, and six compared acupuncture combined with conventional medicine versus conventional medicine. Acupuncture combined with mesalazine showed better clinical effect (improved clinical symptoms, colonoscopy results and stool examination results) (RR 1.25, 95% CI 1.19 to 1.41; 232 participants; 4 trials; low quality evidence) and better colonoscopy curative effect (RR 1.33, 95% CI 1.04 to 1.71; 108 participants; 2 trials; moderate quality evidence) compared to mesalazine. Acupuncture showed better clinical effect compared to the combination of metronidazole and sulfasalazine (RR 1.21, 95%CI 1.10, 1.34; 318 participants; 3 trials; moderate quality evidence). There was no significant difference in the incidence of adverse events between groups.

Conclusions

Both acupuncture alone and acupuncture combined with conventional medicine may be effective in treating ulcerative colitis compared to conventional medicine. Our findings must be interpreted with caution due to high or unclear risk of bias of the included trials.
Correction to: The antibacterial activity and toxin production control of bee venom in mouse MRSA pneumonia model
Authors: Kwon Dong-Yeul , Kong Ryong , Lee Young-Seob , Kang Dam-Hee , Wang Shu , Li Qianqian , Kang Ok-Hwa
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Early warning signals in psychopathology: what do they tell?
Authors: Schreuder Marieke J. , Hartman Catharina A. , George Sandip V. , Menne-Lothmann Claudia , Decoster Jeroen , van Winkel Ruud , Delespaul Philippe , De Hert Marc , Derom Catherine , Thiery Evert , Rutten Bart P. F. , Jacobs Nele , van Os Jim , Wigman Johanna T. W. , Wichers Marieke
Published: October 2020

Background

Despite the increasing understanding of factors that might underlie psychiatric disorders, prospectively detecting shifts from a healthy towards a symptomatic state has remained unattainable. A complex systems perspective on psychopathology implies that such symptom shifts may be foreseen by generic indicators of instability, or early warning signals (EWS). EWS include, for instance, increasing variability, covariance, and autocorrelation in momentary affective states—of which the latter was studied. The present study investigated if EWS predict (i) future worsening of symptoms as well as (ii) the type of symptoms that will develop, meaning that the association between EWS and future symptom shifts would be most pronounced for congruent affective states and psychopathological domains (e.g., feeling down and depression).

Methods

A registered general population cohort of adolescents (mean age 18 years, 36% male) provided ten daily ratings of their affective states for 6 consecutive days. The resulting time series were used to compute EWS in feeling down, listless, anxious, not relaxed, insecure, suspicious, and unwell. At baseline and 1-year follow-up, symptom severity was assessed by the Symptom Checklist-90 (SCL-90). We selected four subsamples of participants who reported an increase in one of the following SCL-90 domains: depression (N = 180), anxiety (N = 192), interpersonal sensitivity (N = 184), or somatic complaints (N = 166).

Results

Multilevel models showed that EWS in feeling suspicious anticipated increases in interpersonal sensitivity, as hypothesized. EWS were absent for other domains. While the association between EWS and symptom increases was restricted to the interpersonal sensitivity domain, post hoc analyses showed that symptom severity at baseline was related to heightened autocorrelations in congruent affective states for interpersonal sensitivity, depression, and anxiety. This pattern replicated in a second, independent dataset.

Conclusions

The presence of EWS prior to symptom shifts may depend on the dynamics of the psychopathological domain under consideration: for depression, EWS may manifest only several weeks prior to a shift, while for interpersonal sensitivity, EWS may already occur 1 year in advance. Intensive longitudinal designs where EWS and symptoms are assessed in real-time are required in order to determine at what timescale and for what type of domain EWS are most informative of future psychopathology.
Incidence of idiopathic cardiomyopathy in patients with type 2 diabetes in Taiwan: age, sex, and urbanization status-stratified analysis
Authors: Chen Hua-Fen , Chang Ya-Hui , Lo Hsien-Jung , Isfandiari Muhammad Atoillah , Martini Santi , Hou Wen-Hsuan , Li Chung-Yi
Published: October 2020

Background

The epidemiology of diabetes and idiopathic cardiomyopathy have limited data. We investigated the overall and the age-, sex-, and urbanization-specific incidence and relative hazard of idiopathic cardiomyopathy in association with type 2 diabetes and various anti-diabetic medications used in Taiwan.

Methods

A total of 474,268 patients with type 2 diabetes were identified from ambulatory care and inpatient claims in 2007–2009 from Taiwan’s National Health Insurance (NHI) database. We randomly selected 474,266 age-, sex-, and diagnosis date-matched controls from the registry of NHI beneficiaries. All study subjects were linked to ambulatory care and inpatient claims (up to the end of 2016) to identify the possible diagnosis of idiopathic cardiomyopathy. The person-year approach with Poisson assumption was used to estimate the incidence, and Cox proportional hazard regression model with Fine and Gray’s method was used to estimate the relative hazards of idiopathic cardiomyopathy in relation to type 2 diabetes.

Results

The overall incidence of idiopathic cardiomyopathy for men and women patients, respectively, was 3.83 and 2.94 per 10,000 person-years, which were higher than the corresponding men and women controls (2.00 and 1.34 per 10,000 person-years). Compared with the control group, patients with type 2 diabetes were significantly associated with an increased hazard of idiopathic cardiomyopathy (adjusted hazard ratio [aHR]: 1.60, 95% confidence interval [CI]: 1.45–1.77] in all age and sex stratifications except in those men aged > 64 years. Patients with type 2 diabetes aged < 45 years confronted the greatest increase in the hazard of idiopathic cardiomyopathy, with an aHR of 3.35 (95% CI 2.21–5.06) and 3.48 (95% CI 1.60–7.56) for men and women, respectively. The usage of some anti-diabetic medications revealed lower risks of idiopathic cardiomyopathy.

Conclusions

In Taiwan, diabetes increased the risk of idiopathic cardiomyopathy in both sexes and in all age groups, except in men aged > 64 years. Younger patients were vulnerable to have higher HRs of idiopathic cardiomyopathy. Some anti-diabetic medications may reduce the risks of cardiomyopathy.
PET imaging of P2X7R in the experimental autoimmune encephalomyelitis model of multiple sclerosis using [11C]SMW139
Authors: Beaino Wissam , Janssen Bieneke , Kooijman Esther , Vos Ricardo , Schuit Robert C. , O’Brien-Brown James , Kassiou Michael , van het Hof Bert , Vugts Danielle J. , de Vries Helga E. , Windhorst Albert D.
Published: October 2020

Background

Non-invasive imaging of the activation status of microglia and the ability to identify a pro- or anti-inflammatory environment can provide valuable insights not only into pathogenesis of neuro-inflammatory and neurodegenerative diseases but also the monitoring of the efficacy of immunomodulatory therapies. P2X7R is highly expressed on pro-inflammatory microglia and [11C]SMW139, a specific P2X7R tracer for positron emission tomography imaging, showed good pharmacokinetics, stability, and brain permeability in vivo. Our objective was to evaluate the potential of [11C]SMW139 for PET imaging of neuroinflammation in vivo in the experimental autoimmune encephalomyelitis (EAE) model.

Methods

We induced EAE in Lewis rats by immunization with MBP 69-88 in complete Freund’s adjuvant (CFA). We determined the affinity of [11C]SMW139 to human and rat P2X7R using saturation binding assay. Using this tracer, PET imaging was performed at the peak of disease and in the recovery phase. In vivo blocking experiments were conducted to validate the specific brain uptake of the tracer. Immunohistochemistry staining and autoradiography were performed to evaluate the level of neuroinflammation and validate the specific binding of [11C]SMW139.

Results

[11C]SMW139 showed good affinity for the rat P2X7R with a Kd of 20.6 ± 1.7 nM. The uptake of [11C]SMW139 was significantly higher in EAE animals at the peak of disease compared to the recovery phase but not in CFA control animals. The amplitude of increase of [11C]SMW139 uptake showed significant positive correlation with clinical scores mainly in the spinal cord (Pearson = 0.75, Spearman = 0.76; p < 0.0001). Treating EAE animals with P2X7R antagonist JNJ-47965567 blocked the uptake of [11C]SMW139 in the spinal cord, cerebellum, and brain stem, demonstrating specific accumulation of the tracer. P-glycoprotein blocking with tariquidar (30 mg/kg) did not affect tracer penetration in the brain showing that [11C]SMW139 is not a Pgp substrate.

Conclusion

Our data shows that [11C]SMW139 is a promising PET tracer for imaging neuroinflammation and evaluating the dynamics of pro-inflammatory microglia in the brain. This can provide crucial insights into the role of microglia in disease progression and enables the development of novel treatment strategies aimed at modulating the immune response in order to promote neuroprotection.
The overexpression of TDP-43 in astrocytes causes neurodegeneration via a PTP1B-mediated inflammatory response
Authors: Lee Shinrye , Kim Seyeon , Kang Ha-Young , Lim Hye Ryeong , Kwon Younghwi , Jo Myungjin , Jeon Yu-Mi , Kim Sang Ryong , Kim Kiyoung , Ha Chang Man , Lee Seongsoo , Kim Hyung-Jun
Published: October 2020

Background

Cytoplasmic inclusions of transactive response DNA binding protein of 43 kDa (TDP-43) in neurons and astrocytes are a feature of some neurodegenerative diseases, such as frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). However, the role of TDP-43 in astrocyte pathology remains largely unknown.

Methods

To investigate whether TDP-43 overexpression in primary astrocytes could induce inflammation, we transfected primary astrocytes with plasmids encoding Gfp or TDP-43-Gfp. The inflammatory response and upregulation of PTP1B in transfected cells were examined using quantitative RT-PCR and immunoblot analysis. Neurotoxicity was analysed in a transwell coculture system of primary cortical neurons with astrocytes and cultured neurons treated with astrocyte-conditioned medium (ACM). We also examined the lifespan, performed climbing assays and analysed immunohistochemical data in pan-glial TDP-43-expressing flies in the presence or absence of a Ptp61f RNAi transgene.

Results

PTP1B inhibition suppressed TDP-43-induced secretion of inflammatory cytokines (interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)) in primary astrocytes. Using a neuron-astrocyte coculture system and astrocyte-conditioned media treatment, we demonstrated that PTP1B inhibition attenuated neuronal death and mitochondrial dysfunction caused by overexpression of TDP-43 in astrocytes. In addition, neuromuscular junction (NMJ) defects, a shortened lifespan, inflammation and climbing defects caused by pan-glial overexpression of TDP-43 were significantly rescued by downregulation of ptp61f (the Drosophila homologue of PTP1B) in flies.

Conclusions

These results indicate that PTP1B inhibition mitigates the neuronal toxicity caused by TDP-43-induced inflammation in mammalian astrocytes and Drosophila glial cells.
Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro
Authors: Ding Bo , Lin Chengheng , Liu Qian , He Yingying , Ruganzu John Bosco , Jin Hui , Peng Xiaoqian , Ji Shengfeng , Ma Yanbing , Yang Weina
Published: October 2020

Background

Glial activation and neuroinflammation play a crucial role in the pathogenesis and development of Alzheimer’s disease (AD). The receptor for advanced glycation end products (RAGE)-mediated signaling pathway is related to amyloid beta (Aβ)-induced neuroinflammation. This study aimed to investigate the neuroprotective effects of tanshinone IIA (tan IIA), a natural product isolated from traditional Chinese herbalSalvia miltiorrhizaBunge, against Aβ-induced neuroinflammation, cognitive impairment, and neurotoxicity as well as the underlying mechanisms in vivo and in vitro.

Methods

Open-field test, Y-maze test, and Morris water maze test were conducted to assess the cognitive function in APP/PS1 mice. Immunohistochemistry, immunofluorescence, thioflavin S (Th-S) staining, enzyme-linked immunosorbent assay (ELISA), real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and western blotting were performed to explore Aβ deposition, synaptic and neuronal loss, microglial and astrocytic activation, RAGE-dependent signaling, and the production of pro-inflammatory cytokines in APP/PS1 mice and cultured BV2 and U87 cells.

Results

Tan IIA treatment prevented spatial learning and memory deficits in APP/PS1 mice. Additionally, tan IIA attenuated Aβ accumulation, synapse-associated proteins (Syn and PSD-95) and neuronal loss, as well as peri-plaque microgliosis and astrocytosis in the cortex and hippocampus of APP/PS1 mice. Furthermore, tan IIA significantly suppressed RAGE/nuclear factor-κB (NF-κB) signaling pathway and the production of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in APP/PS1 mice and cultured BV2 and U87 cells.

Conclusions

Taken together, the present results indicated that tan IIA improves cognitive decline and neuroinflammation partly via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro. Thus, tan IIA might be a promising therapeutic drug for halting and preventing AD progression.
Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinoma
Authors: Lee Hong Kyu , Kwon Mi Jung , Ra Yong Joon , Lee Hee Sung , Kim Hyoung Soo , Nam Eun Sook , Cho Seong Jin , Park Hye-Rim , Min Soo Kee , Seo Jinwon , Choe Ji-Young , Min Kyueng-Whan , Kang So Young
Published: October 2020

Background

Esophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, and BRAF mutations, microsatellite instability (MSI) caused by deficient mismatch repair (dMMR), and human papillomavirus (HPV) can potentially upregulate PD-L1 expression, which might contribute to the clinical outcome of patients with ESCC.

Methods

We investigated the significance of the present druggable markers [PD-L1, PIK3CA, KRAS, and BRAF mutations, MSI caused by deficient dMMR, and HPV] in 64 curatively resected ESCCs, using immunohistochemistry (PD-L1 and MMR protein expression), direct sequencing (KRAS, BRAF, and PIK3CA mutations), real-time PCR (HPV infection), and MSI using quasi-monomorphic markers.

Results

PD-L1 expression, PIK3CA mutation, and MSI/dMMR were detected in 35.9, 12.5, and 17.2% of ESCCs, respectively. HPV was rarely detected (1.6%) (high-risk HPV68), whereas KRAS and BRAF mutations were not detected in ESCCs. PD-L1-positive tumors were not correlated with PIK3CA mutation or MSI/dMMR (all P > 0.05). PD-L1, PIK3CA mutation, and MSI/dMMR characterized the patients associated with light smoking, female and younger age, and younger age and well-differentiated tumors, respectively (all P < 0.05). In multivariate analysis, only PD-L1-positivity was an independent favorable prognostic factor for overall survival (OS) and disease-free survival (DFS) (P = 0.023, P = 0.014). In the PD-L1-negative ESCCs, PIK3CA mutation had a poor prognostic impact on both OS and DFS (P = 0.006, P = 0.002).

Conclusions

PIK3CA mutation may be an alternative prognostic biomarker in PD-L1-negative curatively resected ESCCs that can be optional to identify high-risk patients with worse clinical outcome who require more intensive therapy and follow-up.
Ethnobotanical study on plants used for traditional beekeeping by Dulong people in Yunnan, China
Authors: Cheng Zhuo , Luo Binsheng , Fang Qiong , Long Chunlin
Published: October 2020

Background

The Dulong (Drung) people have used plant materials in traditional beekeeping for many decades. However, there are few studies on the plants used in traditional beekeeping. Furthermore, traditional ecological knowledge (TEK) associated with beekeeping is still poorly understood. TEK and plants associated with beekeeping play an important role in the conservation of native bees and the development of beekeeping. It is therefore very urgent to investigate, record, and study the plants and TEK of Dulong beekeeping.

Methods

Fieldwork was conducted in the Dulong community of Gongshan County, Yunnan Province, China. Six Dulong villages were investigated. Ethnobotanical methods such as free listing, semi-structured interviews, participatory observation, and key informant interviews were used to collect data. A total of 42 Dulong respondents provided information about plants used in traditional beekeeping. TEK related to traditional beekeeping plants was documented. Citation frequency, abundance, and preference ranking of log beehive plant species were used to identify plant resources that are “easier to obtain” and “more preferred.”

Results

There are two general methods of traditional Dulong beekeeping: living tree beekeeping and log beehive beekeeping. The investigation revealed that 38 species (in 19 families), including 30 tree species, 5 bamboo species, 2 herbaceous species, and 1 liana species, are used in traditional Dulong beekeeping. Different plant parts are used for different purposes. Twenty-seven tree species are used to make log beehives. Species from the family Pinaceae and Fagaceae are the most frequently represented. Seven of the most commonly reported species used to build log beehives were scored by ten beekeepers. Based on this scoring, the beekeepers’ most preferred species for making log beehives are Alnus nepalensis, Pinus yunnanensis, and Juglans regia.

Conclusion

The Dulong people have used various plants for traditional beekeeping and have accumulated rich TEK associated with apiculture. Future research will include a nutritive components analysis of honey from traditional Dulong beekeeping and an ethnobotanical investigation of melliferous species used in traditional Dulong apicultural systems. The application of plants and TEK associated with beekeeping is important for improving livelihoods in local communities, conserving biocultural diversity, and protecting the eco-environment of the Dulongjiang area.
Informing urban climate planning with high resolution data: the Hestia fossil fuel CO2 emissions for Baltimore, Maryland
Authors: Roest Geoffrey S. , Gurney K. R. , Miller S. M. , Liang J.
Published: October 2020

Background

Cities contribute more than 70% of global anthropogenic carbon dioxide (CO2) emissions and are leading the effort to reduce greenhouse gas (GHG) emissions through sustainable planning and development. However, urban greenhouse gas mitigation often relies on self-reported emissions estimates that may be incomplete and unverifiable via atmospheric monitoring of GHGs. We present the Hestia Scope 1 fossil fuel CO2(FFCO2) emissions for the city of Baltimore, Maryland—a gridded annual and hourly emissions data product for 2010 through 2015 (Hestia-Baltimore v1.6). We also compare the Hestia-Baltimore emissions to overlapping Scope 1 FFCO2emissions in Baltimore’s self-reported inventory for 2014.

Results

The Hestia-Baltimore emissions in 2014 totaled 1487.3 kt C (95% confidence interval of 1158.9–1944.9 kt C), with the largest emissions coming from onroad (34.2% of total city emissions), commercial (19.9%), residential (19.0%), and industrial (11.8%) sectors. Scope 1 electricity production and marine shipping were each generally less than 10% of the city’s total emissions. Baltimore’s self-reported Scope 1 FFCO2emissions included onroad, natural gas consumption in buildings, and some electricity generating facilities within city limits. The self-reported Scope 1 FFCO2total of 1182.6 kt C was similar to the sum of matching emission sectors and fuels in Hestia-Baltimore v1.6. However, 20.5% of Hestia-Baltimore’s emissions were in sectors and fuels that were not included in the self-reported inventory. Petroleum use in buildings were omitted and all Scope 1 emissions from industrial point sources, marine shipping, nonroad vehicles, rail, and aircraft were categorically excluded.

Conclusions

The omission of petroleum combustion in buildings and categorical exclusions of several sectors resulted in an underestimate of total Scope 1 FFCO2emissions in Baltimore’s self-reported inventory. Accurate Scope 1 FFCO2emissions, along with Scope 2 and 3 emissions, are needed to inform effective urban policymaking for system-wide GHG mitigation. We emphasize the need for comprehensive Scope 1 emissions estimates for emissions verification and measuring progress towards Scope 1 GHG mitigation goals using atmospheric monitoring.
Design and feasibility of a novel program of cervical screening in Nigeria: self-sampled HPV testing paired with visual triage
Authors: Desai Kanan T. , Ajenifuja Kayode O. , Banjo Adekunbiola , Adepiti Clement A. , Novetsky Akiva , Sebag Cathy , Einstein Mark H. , Oyinloye Temitope , Litwin Tamara R. , Horning Matt , Olanrewaju Fatai Olatunde , Oripelaye Mufutau Muphy , Afolabi Esther , Odujoko Oluwole O. , Castle Philip E. , Antani Sameer , Wilson Ben , Hu Liming , Mehanian Courosh , Demarco Maria , Gage Julia C. , Xue Zhiyun , Long Leonard R. , Cheung Li , Egemen Didem , Wentzensen Nicolas , Schiffman Mark
Published: October 2020

Background

Accelerated global control of cervical cancer would require primary prevention with human papillomavirus (HPV) vaccination in addition to novel screening program strategies that are simple, inexpensive, and effective. We present the feasibility and outcome of a community-based HPV self-sampled screening program.

Methods

In Ile Ife, Nigeria, 9406 women aged 30–49 years collected vaginal self-samples, which were tested for HPV in the local study laboratory using Hybrid Capture-2 (HC2) (Qiagen). HPV-positive women were referred to the colposcopy clinic. Gynecologist colposcopic impression dictated immediate management; biopsies were taken when definite acetowhitening was present to produce a histopathologic reference standard of precancer (and to determine final clinical management). Retrospective linkage to the medical records identified 442 of 9406 women living with HIV (WLWH).

Results

With self-sampling, it was possible to screen more than 100 women per day per clinic. Following an audio-visual presentation and in-person instructions, overall acceptability of self-sampling was very high (81.2% women preferring self-sampling over clinician collection). HPV positivity was found in 17.3% of women. Intensive follow-up contributed to 85.9% attendance at the colposcopy clinic. Of those referred, 8.2% were initially treated with thermal ablation and 5.6% with large loop excision of transformation zone (LLETZ). Full visibility of the squamocolumnar junction, necessary for optimal visual triage and ablation, declined from 68.5% at age 30 to 35.4% at age 49. CIN2+ and CIN3+ (CIN- Cervical intraepithelial neoplasia), including five cancers, were identified by histology in 5.9 and 3.2% of the HPV-positive women, respectively (0.9 and 0.5% of the total screening population), leading to additional treatment as indicated. The prevalences of HPV infection and CIN2+ were substantially higher (40.5 and 2.5%, respectively) among WLWH. Colposcopic impression led to over- and under-treatment compared to the histopathology reference standard.

Conclusion

A cervical cancer screening program using self-sampled HPV testing, with colposcopic immediate management of women positive for HPV, proved feasible in Nigeria. Based on the collected specimens and images, we are now evaluating the use of a combination of partial HPV typing and automated visual evaluation (AVE) of cervical images to improve the accuracy of the screening program.
Hemophagocytic lymphohistiocytosis in a patient with COVID-19 treated with tocilizumab: a case report
Authors: Tholin Birgitte , Hauge Marit Teigen , Aukrust Pål , Fehrle Lutz , Tvedt Tor Henrik
Published: October 2020

Background

The understanding of coronavirus disease 2019 (COVID-19) is rapidly evolving. Although it is primarily a respiratory illness, other manifestations, such as Guillain-Barré syndrome, immune thrombocytopenia, and immune-mediated thrombotic thrombocytopenic purpura, have been described. We present a case of a patient with hemophagocytic lymphohistiocytosis secondary to COVID-19 treated with tocilizumab with a marked biochemical improvement.

Case presentation

In this case report we present a Caucasian patient with COVID-19 who developed a marked elevation of inflammatory parameters with ferritin 36,023 μg/L, but also elevated C-reactive protein 334 mg/L and lactate dehydrogenase 1074 U/L, 1 week after admission to the intensive care unit. He met five of eight criteria for hemophagocytic lymphohistiocytosis, but he lacked the high fever and cytopenia seen in the majority of cases. He was treated with tocilizumab, a monoclonal antibody targeting the interleukin-6 receptor, and over the next days, a rapid decrease in ferritin and C-reactive protein levels was observed. However, his respiratory failure only improved gradually, and he was weaned off the respirator 11 days later.

Conclusion

COVID-19 may induce a hyperinflammatory clinical picture and in some cases develop into hemophagocytic lymphohistiocytosis. In our patient’s case, therapeutic interleukin-6 blockade abrogated signs of hyperinflammation but did not seem to improve pulmonary function. Measurement of ferritin and C-reactive protein, as well as quantification of interleukin-6 on indication, should be performed in patients with severe COVID-19. Specific treatment in such patients must also be contemplated, preferably in randomized controlled trials.
Energy-efficient capture of stochastic events based on on-line scheduling scheme
Authors: Fu Xiao , Cheng Zongmao , Tan Hao
Published: October 2020

We improve the off-line scheduling scheme of existing wireless sensor network. Firstly, we introduce Bayesian statistical method in synchronous wireless sensor network. Then, we let duration and interval, the reflection of characteristics of stochastic events, obey exponential distribution. Next, we make Bayes posterior estimation on parameter. Based on Bayesian estimate, we obtain the analytical solution of the capture probability of stochastic events and sensor energy efficiency of capture events. Finally, we propose an on-line scheduling scheme for synchronous wireless sensor networks. This paper compares and analyzes the simulation experiments in on-line scheduling scheme and off-line scheduling scheme, and the results show that compared with off-line scheduling scheme with constant distribution parameter values, on-line scheduling scheme can effectively reduce the probability of missing stochastic events and increase the probability of capturing events, further save energy consumption of wireless sensor network, and extend network lifetime.