bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical Validation of Telomere Analysis Technology® for the High-Throughput Analysis of Multiple Telomere-Associated Variables
Authors: de Pedro Nuria , Díez María , García Irene , García Jorge , Otero Lissette , Fernández Luis , García Beatriz , González Rut , Rincón Sara , Pérez Diego , Rodríguez Estefanía , Segovia Enrique , Najarro Pilar
Published: January 2020

Background

A large number of studies have suggested a correlation between the status of telomeres and disease risk. High-throughput quantitative fluorescence in situ hybridization (HT Q-FISH) is a highly accurate telomere measurement technique that can be applied to the study of large cell populations. Here we describe the analytical performance testing and validation of Telomere Analysis Technology (TAT®), a laboratory-developed HT Q-FISH-based methodology that includes HT imaging and software workflows that provide a highly detailed view of telomere populations.

Methods

TAT was developed for the analysis of telomeres in peripheral blood mononuclear cells (PBMCs). TAT was compared with Terminal Restriction Fragment (TRF) length analysis, and tested for accuracy, precision, limits of detection (LOD) and specificity, reportable range and reference range.

Results

Using 6 different lymphocyte cell lines, we found a high correlation between TAT and TRF for telomere length (R2 ≥ 0.99). The standard variation (assay error) of TAT was 454 base pairs, and the limit of detection of 800 base pairs. A standard curve was constructed to cover human median reportable range values and defined its lower limit at 4700 bp and upper limits at 14,400 bp. Using TAT, up to 223 telomere associated variables (TAVs) can be obtained from a single sample. A pilot, population study, of telomere analysis using TAT revealed high accuracy and reliability of the methodology.

Conclusions

Analytical validation of TAT shows that is a robust and reliable technique for the characterization of a detailed telomere profile in large cell populations. The combination of high-throughput imaging and software workflows allows for the collection of a large number of telomere-associated variables from each sample, which can then be used in epidemiological and clinical studies.
Proteomics profiling and pathway analysis of hippocampal aging in rhesus monkeys
Authors: Meng Shu , Xia Wenchao , Pan Meng , Jia Yangjie , He Zhanlong , Ge Wei
Published: January 2020

Background

Aged rhesus monkeys exhibit deficits in memory mediated by the hippocampus. Although extensive research has been carried out on the characteristics of human hippocampal aging, there is still very little scientific understanding of the changes associated with hippocampal aging in rhesus monkeys. To explore the proteomics profiling and pathway-related changes in the rhesus hippocampus during the aging process, we conducted a high throughput quantitative proteomics analysis of hippocampal samples from two groups of rhesus macaques aged 6 years and 20 years, using 2-plex tandem mass tag (TMT) labeling. In addition, we used a comprehensive bioinformatics analysis approach to investigate the enriched signaling pathways of differentially expressed proteins (the ratios of 20-years vs. 6-years, ≥ 1.20 or ≤ 0.83).

Results

In total, 3260 proteins were identified with a high level of confidence in rhesus hippocampus. We found 367 differentially expressed proteins related to rhesus hippocampus aging. Based on biological pathway analysis, we found these aging-related proteins were predominantly enriched in the electron transport chain, NRF2 pathway, focal adhesion–PI3K–AKT–mTOR signaling pathway and cytoplasmic ribosome proteins. Data are available via ProteomeXchange with identifier PXD011398.

Conclusion

This study provides a detail description of the proteomics profile related to rhesus hippocampal aging. These findings should make an important contribution to further mechanistic studies, marker selection and drug development for the prevention and treatment of aging or age-related neurodegeneration.
Needle tract seeding recurrence of pancreatic cancer in the gastric wall with paragastric lymph node metastasis after endoscopic ultrasound-guided fine needle aspiration followed by pancreatectomy: a case report and literature review
Authors: Sato Nami , Takano Shigetsugu , Yoshitomi Hideyuki , Furukawa Katsunori , Takayashiki Tsukasa , Kuboki Satoshi , Suzuki Daisuke , Sakai Nozomu , Kagawa Shingo , Mishima Takashi , Nakadai Eri , Mikata Rintaro , Kato Naoya , Ohtsuka Masayuki
Published: January 2020

Background

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has high accuracy and a low complication rate; therefore, it has been widely used as a useful tool for diagnosis of and to determine treatment strategies for pancreatic tumors. Recently, reports of the recurrence of needle tract seeding after EUS-FNA are emerging.

Case presentation

An 83-year-old woman was referred to our hospital to undergo further examination of her pancreatic tumor. Multidetector computed tomography (MDCT) revealed a 25-mm-diameter mass in the pancreatic body. She underwent EUS-FNA (transgastric, 22-G needle, 2 passes) and was subsequently diagnosed with adenocarcinoma. Distal pancreatosplenectomy followed by adjuvant chemotherapy with S-1 for 6 months was performed. The level of carbohydrate antigen 19–9 gradually increased 22 months after surgery, and MDCT, which was performed 3 months later, revealed a 23-mm low-density mass in the stomach and paragastric lymph node swelling. Gastroendoscopy revealed a submucosal tumor, and endoscopic ultrasound revealed a hypoechoic mass in the submucosa of the gastric wall. Partial gastrectomy with lymph node resection was performed. The pathological findings showed adenocarcinoma extending from the subserosa to the submucosa and lymph node metastasis, consistent with a tumor recurrence from the resected pancreatic tumor. She received adjuvant chemotherapy with S-1; recurrence was not observed for 5 months, at the time of this writing.

Conclusion

It is important to pay careful attention to the development of needle tract seeding in patients with pancreatic cancer diagnosed by EUS-FNA. This is the first case of needle tract seeding with lymph node metastasis, highlighting the need for caution and providing novel insight in the postoperative follow-up of patients with pancreatic body/tail cancer.
Diagnosis of severe community-acquired pneumonia caused by Acinetobacter baumannii through next-generation sequencing: a case report
Authors: Xu Ancong , Zhu Hong , Gao Bingqi , Weng Haixu , Ding Zhangna , Li Mianmian , Weng Xing , He Guoxin
Published: January 2020

Background

Acinetobacter baumannii is a gram-negative aerobic bacillus that is commonly causes of hospital-acquired infections. Community-acquired pneumonia caused by Acinetobacter baumannii (CAP-Ab) is rare but fatal if diagnosis and treatment are delayed. Conventional culture of clinical specimens is the main method for clinical diagnosis of A. baumannii infections which may suffer from limited positive rate and is time consuming. Timely and precise diagnosis of CAP-Ab remains challenging.

Case presentation

A 66-year-old man with 24 h history of acute fever and dyspnea was admitted to our hospital. He was diagnosed as severe community acquired pneumonia (CAP), septic shock, respiratory failure and acute kidney injury. Next-generation sequencing (NGS) was performed on the patient’s sputum and blood, which identified numerous A. baumannii nucleotide sequences in the sample of sputum and led to the rapid diagnosis and treatment of community acquired pneumonia caused by A. baumannii. This result was confirmed by subsequent sputum culture.

Conclusions

This case described that the successful application of the next generation sequencing assisting the speedy diagnosis of A. baumannii infection provides a new idea for the timely diagnosis of CAP-Ab and highlights that NGS is a promising tool in rapid etiological diagnosis of acute and severe infectious diseases.
Hepatitis B testing, treatment, and virologic suppression in HIV-infected patients in Cameroon (ANRS 12288 EVOLCAM)
Authors:   for the EVOLCAM study group, Liégeois Florian , Boyer Sylvie , Eymard-Duvernay Sabrina , Carrieri Patrizia , Kouanfack Charles , Domyeum Jenny , Maradan Gwenaëlle , Ducos Jacques , Mpoudi-Ngolé Eitel , Spire Bruno , Delaporte Eric , Kuaban Christopher , Vidal Laurent , Laurent Christian
Published: January 2020

Background

Hepatitis B is a major concern in Africa, especially in HIV-infected patients. Unfortunately, access to hepatitis B virus (HBV) testing and adequate treatment remains a challenge in the continent. We investigated HBV testing, treatment, and virologic suppression in HIV-infected patients followed up as part of Cameroon’s national antiretroviral programme.

Methods

A cross-sectional survey was performed in adult patients receiving antiretroviral therapy (ART) in 19 hospitals in the Centre and Littoral regions in Cameroon. The proportions of patients tested for hepatitis B surface antigen (HBsAg) prior to the study were compared among all study hospitals using the Chi-square test. The association of individual and hospital-related characteristics with HBV testing and virologic suppression was assessed using multilevel logistic regression models.

Results

Of 1706 patients (women 74%, median age 42 years, median time on ART 3.9 years), 302 (17.7%) had been tested for HBsAg prior to the study. The proportion of HBV-tested patients ranged from 0.8 to 72.5% according to the individual hospital (p < 0.001). HBV testing was lower in women (adjusted odds ratio [aOR] 0.64, 95% confidence interval [CI] 0.46–0.89, p = 0.010) and higher in patients who initiated ART in 2010 or later (aOR 1.66, 95% CI 1.23–2.27, p < 0.001). Of 159 HBsAg-positive patients at the time of the study (9.3%), only 97 (61.0%) received Tenofovir + Lamivudine (or Emtricitabine). Of 157 coinfected patients, 114 (72.6%) had a HBV viral load < 10 IU/mL. HBV suppression was higher in patients with a HIV viral load < 300 copies/mL (aOR 3.46, 95% CI 1.48–8.09, p = 0.004) and lower in patients with increased ALT level (aOR 0.86 per 10 IU/mL increase, 95% CI 0.75–0.97, p = 0.019).

Conclusions

A substantial proportion of HIV/HBV coinfected patients were at higher risk of liver disease progression. Improving the management of HBV infection in the routine healthcare setting in Africa is urgently required in order to achieve the 2030 elimination targets. Micro-elimination of HBV infection in people living with HIV could be an easier and cost-effective component than more widely scaling up HBV policies.
Malignant transformation of pleomorphic xanthoastrocytoma and differential diagnosis: case report
Authors: Watanabe Noriyuki , Ishikawa Eiichi , Kohzuki Hidehiro , Sakamoto Noriaki , Zaboronok Alexander , Matsuda Masahide , Shibuya Makoto , Matsumura Akira
Published: January 2020

Background

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic glioma, characterized by large pleomorphic and frequently multinucleated cells, spindle and lipidized cells, a dense pericellular reticulin network, and numerous eosinophilic granular bodies according to the grade II glial tumor standards of the World Health Organization’s (WHO) 2016 guidelines. PXA rarely transforms into anaplastic PXA or glioblastoma (GBM) and anaplastic PXA, classified as WHO grade III, has a more aggressive clinical behavior with poorer prognosis than PXA.

Case presentation

Here we describe an unusual case of PXA in a 19-year-old woman, first admitted with headache and a mass in the left temporal lobe in 2005 that was removed. Twelve years later, she returned with left temporal headache, diplopia and tinnitus. A local tumor recurrence was found, and a second resection was performed. The specimen showed highly malignant findings, such as necrosis, microvascular proliferation, and multiple mitoses. The integrated diagnosis was made as high grade glioma, probably derived from PXA. Immunohistochemical (IHC) stains were positive for oligo2, and approximately 21% positive for Ki-67, while negative for CD34, IDH1 R132H. INI1 and ATRX were retained. As the histological classification was glioblastoma, the patient received GBM-appropriate chemotherapy and radiation therapy and outpatient follow-ups have demonstrated no obvious symptoms for 1 year after surgery. Additional molecular analyses found BRAF V600E mutations in both resections, supporting the idea that the recurrent tumor had derived from PXA.

Conclusions

This case highlights the complexities of differential diagnosis based on the World Health Organization’s 2016 guidelines. More integrated criteria to differentiate anaplastic PXA from GBM and epithelioid GBM, combined with genetic screening results, might be needed.
Posttraumatic stress disorder and risk of selected autoimmune diseases among US military personnel
Authors: Bookwalter Deborah Boggs , Roenfeldt Kimberly A. , LeardMann Cynthia A. , Kong So Yeon , Riddle Mark S. , Rull Rudolph P.
Published: January 2020

Background

Increasing evidence suggests a link between posttraumatic stress disorder (PTSD) and physical health. Stress disorders may lead to impairment of the immune system and subsequent autoimmune disease. This study investigated the association between PTSD and risk of selected autoimmune diseases (i.e. rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, and multiple sclerosis) among US active duty service members.

Methods

Using data from the Millennium Cohort Study, incident autoimmune cases between study initiation and September 2015 were identified from medical encounter records in the Military Health System Data Repository (MDR). Participants were classified as having a history of PTSD if they self-reported receiving a health care provider’s diagnosis of PTSD or if they screened positive using the PTSD Checklist−Civilian Version. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models adjusted for demographics and history of another mental health condition.

Results

Among 120,572 participants followed for a mean of 5.2 years, risk of any of the selected autoimmune diseases was 58% higher for those with a history of PTSD (HR = 1.58, 95% CI: 1.25, 2.01) compared with no history of PTSD. Further adjustment for BMI, smoking status, and alcohol use had little impact on the effect estimates, and results were not appreciably different according to combat experience and history of physical or sexual trauma.

Conclusions

Active duty military personnel with PTSD may have an elevated risk of a range of autoimmune diseases, regardless of combat experience or prior trauma. Future research is needed to understand potential mechanisms which may inform future mitigative strategies in reducing extra-neuropsychiatric health problems among those with PTSD.
Evaluation of sleep quality and daytime somnolence in patients with chronic obstructive pulmonary disease in pulmonary rehabilitation
Authors: Nobeschi Leandro , Zangirolami-Raimundo Juliana , Cordoni Priscila Kessar , Squassoni Selma Denis , Fiss Elie , Pérez-Riera Andrés Ricardo , de Abreu Luiz Carlos , Raimundo Rodrigo Daminello
Published: January 2020

Background

Dyspnea, fatigue, and decline in sleep quality are symptoms of chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation programs have been shown to ameliorate dyspnea and fatigue. However, only a few studies have investigated the effects of pulmonary rehabilitation on the sleep quality of COPD patients. In this study, we analyzed the benefits of a pulmonary rehabilitation program to sleep quality and daytime somnolence in COPD patients.

Methods

This study was a study of 30 moderate-severe COPD patients. All patients were evaluated by a pulmonologist and underwent polysomnography before participating in the study. For this study, we selected only ex-smokers and patients with sleep apnea were referred to the sleep clinic. These participants were prospectively recruited and not selected based on program completion. Before the start of the program, sleep quality and daytime somnolence of the participants were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS), respectively. Rehabilitation program consisted of muscular training sessions conducted at the gym 3 times per week for 12 weeks. After rehabilitation program, the patients were reassessed and their sleep quality and daytime somnolence were reevaluated using the PSQI and the ESS, respectively.

Results

Before rehabilitation, PSQI evaluation revealed that 73% of the participants had poor sleep quality, and ESS evaluation showed that 86.7% of the participants experienced daytime somnolence. After pulmonary rehabilitation, the PSQI specifically improved in terms of subjective sleep quality and sleep duration (< 0.001), habitual sleep efficiency (0.001), and sleep latency and sleep alterations (0.002) and there was also improvement in the ESS (< 0.001).

Conclusion

Pulmonary rehabilitation program of gradually increasing intensity has the potential to provide sleep-related benefits to patients with COPD who have poor sleep quality and daytime somnolence.

Trial registration

Registro Brasileiro de Ensaios Clínicos (ReBEC) RBR62b4z2.
Development of a Greek Oral health literacy measurement instrument: GROHL
Authors: Taoufik Konstantina , Divaris Kimon , Kavvadia Katerina , Koletsi-Kounari Haroula , Polychronopoulou Argy
Published: January 2020

Background

Oral health literacy is an important construct for both clinical and public health outcomes research. The need to quantify and test OHL has led to the development of measurement instruments and has generated a substantial body of recent literature. A commonly used OHL instrument is REALD-30, a word recognition scale that has been adapted for use in several languages. The objective of this study was the development and testing of the Greek language oral health literacy measurement instrument (GROHL).

Methods

Data from 282 adult patients of two private dental clinics in Athens, Greece were collected via in-person interviews. Forty-four words were initially considered and tested for inclusion. Item response theory analysis (IRT) and 2-parameter logistic models assessing difficulty and discriminatory ability were used to identify an optimal scale composition. Internal consistency was examined using Cronbach’s alpha and test-retest reliability was measured using intraclass correlation coefficient (ICC) in a subset of 20 participants over a two-week period. Convergent validity was tested against functional health literacy screening (HLS) items, dental knowledge (DK), oral health behaviors (OHBs), oral health-related quality of life (OHRQoL; OHIP-14 index), as well as self-reported oral and general health status.

Results

From an initial item pool of 44 items that were carried forward to IRT, 12 were excluded due to no or little variance, 10 were excluded due to low item-test correlation, and 2 due to insignificant contribution to the scale, i.e., difficulty parameter estimate with p > 0.05. The twenty remaining items composed the final index which showed favorable internal consistency (alpha = 0.80) and test-retest reliability (ICC = 0.95). The summary score distribution did not depart from normality (p = 0.32; mean = 11.5; median = 12; range = 1–20). GROHL scores were positively correlated with favorable oral hygiene behaviors and dental attendance, as well as HLS, DK and education level.

Conclusion

The GROHL demonstrated good psychometric properties and can be used for outcomes research in clinical and public health settings.
An EAPC white paper on multi-disciplinary education for spiritual care in palliative care
Authors: Best Megan , Leget Carlo , Goodhead Andrew , Paal Piret
Published: January 2020

Background

The EAPC White Paper addresses the issue of spiritual care education for all palliative care professionals. It is to guide health care professionals involved in teaching or training of palliative care and spiritual care; stakeholders, leaders and decision makers responsible for training and education; as well as national and local curricula development groups.

Methods

Early in 2018, preliminary draft paper was written by members of the European Association for Palliative Care (EAPC) spiritual care reference group inviting comment on the four core elements of spiritual care education as outlined by Gamondi et al. (2013) in their paper on palliative care core competencies. The preliminary draft paper was circulated to experts from the EAPC spiritual care reference group for feedback. At the second stage feedback was incorporated into a second draft paper and experts and representatives of national palliative care organizations were invited to provide feedback and suggest revisions. The final version incorporated the subsequent criticism and as a result, the Gamondi framework was explored and critically revised leading to updated suggestions for spiritual care education in palliative care.

Results

The EAPC white paper points out the importance of spiritual care as an integral part of palliative care and suggests incorporating it accordingly into educational activities and training models in palliative care. The revised spiritual care education competencies for all palliative care providers are accompanied by the best practice models and research evidence, at the same time being sensitive towards different development stages of the palliative care services across the European region.

Conclusions

Better education can help the healthcare practitioner to avoid being distracted by their own fears, prejudices, and restraints and attend to the patient and his/her family. This EAPC white paper encourages and facilitates high quality, multi-disciplinary, academically and financially accessible spiritual care education to all palliative care staff.
Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology
Authors: Zhou Wei , Wu Jiarui , Zhu Yingli , Meng Ziqi , Liu Xinkui , Liu Shuyu , Ni Mengwei , Jia Shanshan , Zhang Jingyuan , Guo Siyu
Published: January 2020

Background

As an effective prescription for gastric cancer (GC), Compound Kushen Injection (CKI) has been widely used even though few molecular mechanism analyses have been carried out.

Methods

In this study, we identified 16 active ingredients and 60 GC target proteins. Then, we established a compound-predicted target network and a GC target protein-protein interaction (PPI) network by Cytoscape 3.5.1 and systematically analyzed the potential targets of CKI for the treatment of GC. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses.

Results

The results showed that the potential targets, including CCND1, PIK3CA, AKT1, MAPK1, ERBB2, and MMP2, are the therapeutic targets of CKI for the treatment of GC. Functional enrichment analysis indicated that CKI has a therapeutic effect on GC by synergistically regulating some biological pathways, such as the cell cycle, pathways in cancer, the PI3K-AKT signaling pathway, the mTOR signaling pathway, and the FoxO signaling pathway. Moreover, molecular docking simulation indicated that the compounds had good binding activity to PIK3CA, AKT1, MAPK1, ERBB2, and MMP2 in vivo.

Conclusion

This research partially highlighted the molecular mechanism of CKI for the treatment of GC, which has great potential in the identification of the effective compounds in CKI and biomarkers to treat GC.
Toxicology studies of aqueous-alcohol extracts of Harpagophytum procumbens subsp. procumbens (Burch.) DC.Ex Meisn. (Pedaliaceae) in female and male rats
Authors: Joshi Kirtan , Parrish Alan , Grunz-Borgmann Elizabeth A. , Gerkovich Mary , Folk William R.
Published: January 2020

Background

A variety of medicinal products prepared from secondary tubers of Harpagophytum procumbens subsp. procumbens (Burch.) DC.ex Meisn. (Devil’s Claw) and H. zeyheri are marketed in Africa, Europe, the United States, South America and elsewhere, where they are used for inflammatory and musculoskeletal conditions such as arthritis, lower back pain, rheumatism and neuralgia, etc. While clinical studies conducted over the last twenty years support the general safety of such products, infrequent gastrointestinal disturbances (diarrhea, nausea, vomiting, abdominal pain), headache, vertigo and hypersensitivity (allergic) reactions (rash, hives and face swelling) have been documented. Sex-related differences occur in the health conditions for which Devil’s Claw products are used, so it is likely that usage is similarly sex-related and so might be side effects and potential toxicities. However toxicologic studies of Devil’s Claw products have been conducted primarily with male animals. To address this deficit, we report toxicological studies in female and male rats of several H. procumbens (HP) aqueous-alcohol extracts chemically analyzed by UPLC-MS.

Methods

Female and male Sprague Dawley rats were studied for one and three months in groups differing by consumption of diets without and with HP extracts at a 7–10-fold human equivalent dose (HED). Sera were analyzed for blood chemistry, and heart, liver, lung, kidney, stomach, and small and large intestine tissues were examined for histopathology. Treatment group differences for blood chemistry were analyzed by ANOVA with Dunnett’s test and significant group differences for endpoints with marginal distributional properties were verified using the Kruskal-Wallis test. Group differences for histopathology were tested using Chi Square analysis.

Results

Significant group by sex-related differences in blood chemistry were detected in both studies. Additionally, several sex-related differences occurred between the studies. However, significant histopathology effects associated with the consumption of the extracts were not detected.

Conclusion

Toxicologic analysis of Devil’s Claw extracts cause significant sex-related effects in blood chemistry. However, in our judgement, none of the observed effects suggest serious toxicity at these doses and durations. Subsequent toxicologic and clinical studies of H. procumbens and other medicines with similar properties should explore in greater detail the basis and consequences of potential sex-related effects.
Therapeutic use of cannabis and cannabinoids: an evidence mapping and appraisal of systematic reviews
Authors: Montero-Oleas Nadia , Arevalo-Rodriguez Ingrid , Nuñez-González Solange , Viteri-García Andrés , Simancas-Racines Daniel
Published: January 2020

Background

Although cannabis and cannabinoids are widely used with therapeutic purposes, their claimed efficacy is highly controversial. For this reason, medical cannabis use is a broad field of research that is rapidly expanding. Our objectives are to identify, characterize, appraise, and organize the current available evidence surrounding therapeutic use of cannabis and cannabinoids, using evidence maps.

Methods

We searched PubMed, EMBASE, The Cochrane Library and CINAHL, to identify systematic reviews (SRs) published from their inception up to December 2017. Two authors assessed eligibility and extracted data independently. We assessed methodological quality of the included SRs using the AMSTAR tool. To illustrate the extent of use of medical cannabis, we organized the results according to identified PICO questions using bubble plots corresponding to different clinical scenarios.

Results

A total of 44 SRs published between 2001 and 2017 were included in this evidence mapping with data from 158 individual studies. We extracted 96 PICO questions in the following medical conditions: multiple sclerosis, movement disorders (e.g. Tourette Syndrome, Parkinson Disease), psychiatry conditions, Alzheimer disease, epilepsy, acute and chronic pain, cancer, neuropathic pain, symptoms related to cancer (e.g. emesis and anorexia related with chemotherapy), rheumatic disorders, HIV-related symptoms, glaucoma, and COPD. The evidence about these conditions is heterogeneous regarding the conclusions and the quality of the individual primary studies. The quality of the SRs was moderate to high according to AMSTAR scores.

Conclusions

Evidence on medical uses of cannabis is broad. However, due to methodological limitations, conclusions were weak in most of the assessed comparisons. Evidence mapping methodology is useful to perform an overview of available research, since it is possible to systematically describe the extent and distribution of evidence, and to organize scattered data.
Buyang Huanwu Tang inhibits cellular epithelial-to-mesenchymal transition by inhibiting TGF-β1 activation of PI3K/Akt signaling pathway in pulmonary fibrosis model in vitro
Authors: Yin Zi-fei , Wei Yang-lin , Wang Xuan , Wang Li-na , Li Xia
Published: January 2020

Background

Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. Buyang Huanwu Tang (BYHWT), a classical traditional Chinese medicine formula, has been widely utilized for the treatment of PF in China. This present study aimed to explore the mechanism of BYHWT in the treatment of PF in vitro.

Methods

TGF-β1 stimulated human alveolar epithelial A549 cells were used as in vitro model for PF. Post the treatment of BYHWT, cell viability was measured by MTT assay, and cell morphology was observed under microscope. The epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, Vimentin) and collagen I (Col I) were detected by western blot, immunofluorescence staining and real-time quantitative polymerase chain reaction. With the co-administration of activators (IGF-1, SC79) and inhibitors (LY294002, MK2206), the effect of BYHWT on PI3K/Akt pathway was analyzed by western blot.

Results

BYHWT inhibited cell growth, and prevented cell morphology changed from epithelial to fibroblasts in TGF-β1 induced A549 cells. BYHWT decreased Vimentin and Col I, while increased E-cadherin at both protein and mRNA levels. Moreover, phosphorylation of PI3K (p-PI3K) and phosphorylation of Akt (p-Akt) were significantly down-regulated by BYHWT in TGF-β1 stimulated A549 cells.

Conclusion

These results indicate that BYHWT suppressed TGF-β1-induced collagen accumulation and EMT of A549 cells by inhibiting the PI3K/Akt signaling pathway. These findings suggest that BYHWT may have potential for the treatment of PF.
Effectiveness of pharmacist home visits for individuals at risk of medication-related problems: a systematic review and meta-analysis of randomised controlled trials
Authors: Abbott Rebecca A. , Moore Darren A. , Rogers Morwenna , Bethel Alison , Stein Ken , Coon Jo Thompson
Published: January 2020

Background

Medication mismanagement is a major cause of both hospital admission and nursing home placement of frail older adults. Medication reviews by community pharmacists aim to maximise therapeutic benefit but also minimise harm. Pharmacist-led medication reviews have been the focus of several systematic reviews, but none have focussed on the home setting.

Review methods

To determine the effectiveness of pharmacist home visits for individuals at risk of medication-related problems we undertook a systematic review and meta-analysis of randomised controlled trials (RCTs). Thirteen databases were searched from inception to December 2018. Forward and backward citation of included studies was also performed. Articles were screened for inclusion independently by two reviewers. Randomised controlled studies of home visits by pharmacists for individuals at risk of medication-related problems were eligible for inclusion. Data extraction and quality appraisal were performed by one reviewer and checked by a second. Random-effects meta-analyses were performed where sufficient data allowed and narrative synthesis summarised all remaining data.

Results

Twelve RCTs (reported in 15 articles), involving 3410 participants, were included in the review. The frequency, content and purpose of the home visit varied considerably. The data from eight trials were suitable for meta-analysis of the effects on hospital admissions and mortality, and from three trials for the effects on quality of life. Overall there was no evidence of reduction in hospital admissions (risk ratio (RR) of 1.01 (95%CI 0.86 to 1.20, I2 = 69.0%, p = 0.89; 8 studies, 2314 participants)), or mortality (RR of 1.01 (95%CI 0.81 to 1.26, I2 = 0%, p = 0.94; 8 studies, 2314 participants)). There was no consistent evidence of an effect on quality of life, medication adherence or knowledge.

Conclusion

A systematic review of twelve RCTs assessing the impact of pharmacist home visits for individuals at risk of medication related problems found no evidence of effect on hospital admission or mortality rates, and limited evidence of effect on quality of life. Future studies should focus on using more robust methods to assess relevant outcomes.
RDL mutations in Guangxi Anopheles sinensis populations along the China–Vietnam border: distribution frequency and evolutionary origin of A296S resistance allele
Authors: Liu Nian , Feng Xiangyang , Qiu Xinghui
Published: January 2020

Background

Malaria is a deadly vector-borne disease in tropical and subtropical regions. Although indigenous malaria has been eliminated in Guangxi of China, 473 confirmed cases were reported in the Northern region of neighbouring Vietnam in 2014. Considering that frequent population movement occurs across the China–Vietnam border and insecticide resistance is a major obstacle in disease vector control, there is a need to know the genotype and frequency of insecticide resistance alleles in Anopheles sinensis populations along the China–Vietnam border and to take action to prevent the possible migration of insecticide resistance alleles across the border.

Methods

Two hundred and eight adults of An. sinensis collected from seven locations in Guangxi along the China–Vietnam border were used in the investigation of individual genotypes of the AsRDL gene, which encodes the RDL gamma-aminobutyric acid (GABA) receptor subunit in An. sinensis. PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) analysis was deployed to genotype codon 345, while direct sequencing of PCR products was conducted to clarify the genotypes for codons 296 and 327 of the AsRDL gene. The genealogical relation of AsRDL haplotypes was analyzed using Network 5.0.

Results

Three putative insecticide resistance related mutations (A296S, V327I and T345S) were detected in all the seven populations of An. sinensis in Guangxi along the China–Vietnam border. The resistance-conferring A296S mutation was found to be widely distributed and present at notably high frequencies (78.8% to 100%). Relatively lower frequencies of mutations V327I (26.9% to 53.2%) and T345S (0% to 28.8%) were observed. The V327I or T345S always occurred in the presence of A296S. Evolutionary analysis of 21 AsRDL haplotypes indicated multiple origins of the A296S and V327I mutations.

Conclusion

The resistance A296S allele was present at high frequencies in the An. sinensis populations along the China–Vietnam border, indicating a risk of resistance to insecticides targeting RDL. The double mutations (A296S + V327I) may have evolved from alleles carrying the A296S mutation by scaffolding the additional mutation V327I, and A296S allele may have multiple evolutionary origins. These findings will help inform strategies for vector control and malaria prevention.
Activation of cannabinoid receptor type 2-induced osteogenic differentiation involves autophagy induction and p62-mediated Nrf2 deactivation
Authors: Xu Aihua , Yang Yang , Shao Yang , Wu Meng , Sun Yongxin
Published: January 2020

Background

Dysfunction in survival and differentiation of osteoblasts commonly occurs in patients with osteoporosis. Cannabinoid receptor type 2 (CNR2) is a major receptor of endocannabinoid system that is crucial for bone mass homeostasis. Our group prior demonstrated that activation of CNR2 signaling promoted osteogenic differentiation of bone marrow derived mesenchymal stem cells in vitro. Autophagy is reported to participate in osteoblastic differentiation. Whether autophagy is regulated by CNR2-mediated cannabinoid signaling is unknown, and how the autophagy-CNR2 interaction affects osteoblastic differentiation requires further elucidation.

Methods

hFOB 1.19 osteoblasts were treated with CNR2 agonists HU308 (5, 10, 25, 50 or 100 nM) and JWH133 (1, 2, 5, 10 or 20 μM) in presence or absence of autophagy inhibitor 3-Methyladenine (3-MA). The differentiation of hFOB 1.19 cells was determined via evaluating their alkaline phosphatase (ALP) activity and mineralization ability (Alizarin red staining). Alterations in autophagy-related molecules and osteogenic markers were analyzed via real-time PCR and/or immunoblotting assays.

Results

hFOB 1.19 cells spontaneously differentiated towards mature osteoblasts under 39 °C, during which CNR2 expression increased, and autophagy was activated. The strongest autophagy flux was observed at 192 h post differentiation─LC3I to LC3II conversion was enhanced and Beclin 1 expression was upregulated considerably, while p62 expression was downregulated. Treatment of HU308 and JWH133 promoted autophagy in a dose-dependent manner, and suppressed mTOR signaling pathway in hFOB 1.19 cells. In CNR2-silenced cells, HU308’s and JWH133’s effects on autophagy were weakened. HU308 and JWH133 enhanced the ALP activity and mineralization, and upregulated the expression of osteogenic markers, osteopontin and osteocalcin, in hFOB 1.19 cells. Intriguingly, such pro-osteogenic effects induced by CNR2 activation were markedly mitigated by 3-MA. In addition to provoking autophagy, CNR2 agonists also reduced nuclear Nrf2 accumulation and increased Keap1 expression. Further, re-expression of p62 inhibited CNR2 agonists-induced Nrf2 degradation.

Conclusions

Osteogenic differentiation induced by CNR2 signaling activation involves autophagy induction and p62-mediated Nrf2 deactivation.
Patient and physician discordance of global disease assessment in juvenile dermatomyositis: findings from the Childhood Arthritis & Rheumatology Research Alliance Legacy Registry
Authors:   the CARRA Juvenile Dermatomyositis Quality Measures Workgroup for the CARRA Registry Investigators, Tory Heather , Zurakowski David , Kim Susan
Published: January 2020

Background

Global disease activity scores (gVAS) capture patient or family (PF) and physician (MD) assessments of disease. This study sought to measure discordance between PF and MD global activity scores in juvenile dermatomyositis (JDM), and determine factors associated with discordance.

Methods

Patients with JDM were included from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry (N = 563). PF and MD gVAS were assessed for discordance, defined as a ≥ 2-point difference. Factors associated with discordant gVAS were compared in univariate analysis. Multivariable regression analysis was used to identify predictors of discordance.

Results

Almost 40% (N = 219) of PF and MD gVAS were discordant. Among discordant scores, 68% of PF rated gVAS ≥2-points above MD, which was associated with calcinosis and lower quality of life and functional scores (p < 0.01). MD gVAS rated ≥2-points above PF in 32%, which was associated with abnormal laboratory results, weakness, arthritis, rash and other skin changes, and current intravenous steroid treatment (p < 0.01). In multivariate analysis, predictors for higher PF rating included calcinosis, lower quality of life and functional scores, while predictors for higher MD rating included rash, calcinosis, nailfold capillaroscopy changes, and current intravenous steroid treatment.

Conclusions

Discordance between PF and MD gVAS was common in this JDM cohort. Overall, higher PF rating was associated with poorer patient reported outcome (PRO) scores, while higher MD rating was associated with poorer objective measures. This suggests PF and MD assessments of gVAS may be measuring different aspects of disease, highlighting the importance of integrating PROs into clinical practice and research.
Patients with enthesitis related arthritis show similar monocyte function pattern as seen in adult axial spondyloarthropathy
Authors: Bhattacharya Shruti , Misra Ramnath , Aggarwal Amita
Published: January 2020

Background

Axial SpA and Enthesitis related arthritis (ERA) patients show strong HLA-B27 association, gut dysbiosis, high toll like receptor (TLR)2 and 4 expression on monocytes, pro-inflammatory cytokine production and elevated levels of TLR4 endogenous ligands [tenascin-c (TNC) and myeloid related protein (MRP)8/14] in serum. Hence, we aimed to understand if these diseases have similar or different monocyte response.

Methods

Fifty adult axial SpA, 52 ERA patients and 25 healthy controls (HC) were enrolled. Cytokine-producing monocyte frequency before and after stimulation with lipopolysaccharide (LPS), peptidoglycan (PG), TNC or MRP8 were measured in whole blood (WB) and synovial fluid mononuclear cells (SFMC) by flow cytometry. Also, IL-6, TNF, MMP3, TNC and MRP8/14 levels were measured in unstimulated and TLR ligand stimulated WB cultures supernatant by ELISA. Finally, the mRNA expression levels of TNF and IL-6 were measured post stimulation with LPS, TNC and MRP8.

Results

At baseline, ERA and axial SpA patients showed similar TNF-α producing monocyte frequency which was higher than HC. MRP8 simulation led to increased TNF-α producing monocyte frequency in ERA than axial SpA. TNC and MRP8 stimulation led to similar IL-6 producing monocyte frequency in axial SpA and ERA patients. Baseline TNF and IL-6 producing monocyte frequency also modestly correlated with disease activity scores. TNF and IL-6 producing monocyte frequency increased in response to TLR stimulation in SFMC from both patients.

In culture supernatants, axial SpA and ERA patients showed similar TNF production at baseline. MRP8 and TNC stimulation led to higher TNF production from ERA. Baseline IL-6 and MMP3 production was higher in ERA while TLR stimulation led to similar IL-6 and MMP3 production from axial SpA and ERA. TNC stimulation led to higher MMP3 production in ERA. mRNA expression in response to TLR stimulation was observed to be similar in axial SpA and ERA.

TNC production was higher in ERA at baseline, while MRP8/14 production was higher in axial SpA than ERA post stimulation.

Conclusion

ERA patients have similar monocyte response to exogenous and endogenous TLR ligands as patients with axial SpA. This suggests that differences between pediatric and adult-onset SpA are minimal and they may have a common pathogenesis.
A comparative study of aged and contemporary Chinese herbal materials by using delayed luminescence technique
Authors: Jia Yusheng , Sun Mengmeng , Shi Yuhua , Zhu Zhihui , van Wijk Eduard , van Wijk Roeland , van Andel Tinde , Wang Mei
Published: January 2020

Background

Investigation of aged Chinese herbal materials will help us to understand their use and sources in ancient time and broaden the historical perspective of Chinese material medica. To reach this aim, the basic understanding of aged herbal materials, including physical and chemical characters, is of great importance. Delayed luminescence (DL) technique was developed as a rapid, direct, systemic, objective and sample loss-free tool to characterize the properties of Chinese herbal materials. In this study, we measured DL values in aged Chinese herbal materials that were transported from Asia to Europe during the 20th century and stored in Naturalis Biodiversity Center and the Utrecht University museum, and compared these with modern material of the same species.

Methods

A hyperbolic function was used to extract four properties from the DL curves of Chinese herbal material from 1900, the 1950s and recently harvested products. Statistical tools, including the Student’s t test, One-way analysis of variance and Principal Component Analysis, were used to differentiate the DL properties of aged and contemporary collections ofGlycyrrhizaspp.Curcuma aromaticaSalisb.,Zingiber officinaleRoscoe,Alpinia officinarumHance andAcorus calamusL.

Results

Our results showed that DL properties were significantly different between historical and contemporary Chinese herbal materials. Changes in DL values were species-dependent: the effects of storage time of DL properties were specific for each species. These outcomes help us not only in the identification of historical Chinese medicine products but also provides valuable data of the effect of storage time on herbal materials.

Conclusion

The simple, direct, rapid, and inexpensive measurements offered by DL provide a novel tool to assess the taxonomic identity of Chinese and other herbal materials and assess the differences in chemical properties with increasing storage time. Our results contribute to the further development of novel digital tools for the quality control of herbal materials.
Nationwide carrier detection and molecular characterization of β-thalassemia and hemoglobin E variants in Bangladeshi population
Authors: Noor Farjana Akther , Sultana Nusrat , Bhuyan Golam Sarower , Islam Md Tarikul , Hossain Mohabbat , Sarker Suprovath Kumar , Islam Khaleda , Khan Waqar Ahmed , Rahman Mujahida , Qadri Syeda Kashfi , Shekhar Hossain Uddin , Qadri Firdausi , Qadri Syed Saleheen , Mannoor Kaiissar
Published: January 2020

Background

ß-thalassemia is one of the most common inherited blood disorders in the world and a major deterrent to the public health of Bangladesh. The management of thalassemia patients requires lifelong frequent blood transfusion and the available treatment options are unsatisfactory. A national policy on thalassemia prevention is mandatory in Bangladesh. However, precise and up-to-date information on the frequency of ß-thalassemia carriers are missing due to lack of accurate diagnostic approaches, limited access to information and absence of national screening program. This study aims to determine the nationwide carrier frequency of hemoglobin E (HbE) and β- thalassemia and mutation spectrum among the carriers using molecular, hematological and biochemical methods.

Methods

The study enrolled a total of 1877 individuals (60.1% male and 39.9% female) aged between 18 and 35 years. Total sample size and its division-wise breakdown were calculated in proportion to national and division-wise population. Venous blood was collected and subjected to CBC analysis and Hb-electrophoresis for each participant. Serum ferritin was measured to detect coexistence of iron deficiency anemia with thalassemia carrier. DNA-based High Resolution Melting (HRM) curve analysis was performed for confirmation of carrier status by mutation detection.

Results

Of 11.89% (95% CI, 10.43–13.35) carriers of β-globin gene mutations, 8.68% (95% CI, 7.41–9.95) had HbE trait (ETT) and 2.24% (95% CI, 1.57–2.91) had beta-thalassemia trait (BTT). Among eight divisions, Rangpur had the highest carrier frequency of 27.1% (ETT-25%, BTT-2.1%), whereas Khulna had the lowest frequency of 4.2% (ETT-4.2% only). Moreover, α- thalassemia, HbD trait, HbE disease, hereditary persistence of HbF were detected in 0.11, 0.16, 0.43 and 0.16% participants, respectively. HRM could identify two individuals with reported pathogenic mutations in both alleles who were erroneously interpreted as carriers by hematological indices. Finally, a total of nine different mutations including a novel mutation (c.151A > G) were detected in the β-globin gene.

Conclusions

Since carrier frequency for both HbE and β-thalassemia is alarmingly high in Bangladesh, a nationwide awareness and prevention program should be made mandatory to halt the current deteriorating situations. Mutation-based confirmation is highly recommended for the inconclusive cases with conventional carrier screening methods to avoid any faulty detection of thalassemia carriers.