bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluid overload after coronary artery bypass graft in patients on maintenance hemodialysis is associated with prolonged time on mechanical ventilation
Authors: da Silva Sirlei Cristina , Consolim-Colombo Fernanda Marciano , Rodrigues Renata Gomes , Gaiotto Fábio Antonio , Hajjar Ludhmila Abrahão , Moysés Rosa Maria Affonso , Elias Rosilene Motta
Published: March 2020

Background

Fluid overload is a risk factor for morbidity, mortality, and prolonged ventilation time after surgery. Patients on maintenance hemodialysis might be at higher risk. We hypothesized that fluid accumulation would be directly associated with extended ventilation time in patients on hemodialysis, as compared to patients with chronic kidney disease not on dialysis (CKD3–4) and patients with normal renal function (reference group).

Methods

This is a prospective observational study that included patients submitted to isolated and elective coronary artery bypass surgery, divided in 3 groups according to time on mechanical ventilation: < 24 h, 24-48 h and > 48 h. The same observer followed patients daily from the surgery to the hospital discharge. Cumulative fluid balance was defined as the sum of daily fluid balance over the first 5 days following surgery.

Results

Patients requiring more than 48 h of ventilation (5.3%) had a lower estimated glomerular filtration rate, were more likely to be on maintenance dialysis, had longer anesthesia time, needed higher dobutamine and noradrenaline infusion following surgery, and had longer hospitalization stay. Multivariate analysis revealed that the fluid accumulation, scores of sequential organ failure assessment in the day following surgery, and the renal function (normal, chronic kidney disease not on dialysis and maintenance hemodialysis) were independently associated with time in mechanical ventilation. Among patients on hemodialysis, the time from the surgery to the first hemodialysis session also accounted for the time on mechanical ventilation.

Conclusions

Fluid accumulation is an important risk factor for lengthening mechanical ventilation, particularly in patients on hemodialysis. Future studies are warranted to address the ideal timing for initiating dialysis in this scenario in an attempt to reduce fluid accumulation and avoid prolonged ventilation time and hospital stay.
Intranasal dexmedetomidine is an effective sedative agent for electroencephalography in children
Authors: Chen Hang , Yang Fei , Ye Mao , Liu Hui , Zhang Jing , Tian Qin , Liu Ruiqi , Yu Qing , Li Shangyingying , Tu Shengfen
Published: March 2020

Background

Intranasal dexmedetomidine (DEX), as a novel sedation method, has been used in many clinical examinations of infants and children. However, the safety and efficacy of this method for electroencephalography (EEG) in children is limited. In this study, we performed a large-scale clinical case analysis of patients who received this sedation method. The purpose of this study was to evaluate the safety and efficacy of intranasal DEX for sedation in children during EEG.

Methods

This was a retrospective study. The inclusion criteria were children who underwent EEG from October 2016 to October 2018 at the Children’s Hospital affiliated with Chongqing Medical University. All the children received 2.5 μg·kg− 1of intranasal DEX for sedation during the procedure. We used the Modified Observer Assessment of Alertness/Sedation Scale (MOAA/S) and the Modified Aldrete score (MAS) to evaluate the effects of the treatment on sedation and resuscitation. The sex, age, weight, American Society of Anesthesiologists physical status (ASAPS), vital signs, sedation onset and recovery times, sedation success rate, and adverse patient events were recorded.

Results

A total of 3475 cases were collected and analysed in this study. The success rate of the initial dose was 87.0% (3024/3475 cases), and the success rate of intranasal sedation rescue was 60.8% (274/451 cases). The median sedation onset time was 19 mins (IQR: 17–22 min), and the sedation recovery time was 41 mins (IQR: 36–47 min). The total incidence of adverse events was 0.95% (33/3475 cases), and no serious adverse events occurred.

Conclusions

Intranasal DEX (2.5 μg·kg− 1) can be safely and effectively used for EEG sedation in children.
Impact of chronic kidney disease and anemia on health-related quality of life and work productivity: analysis of multinational real-world data
Authors: van Haalen Heleen , Jackson James , Spinowitz Bruce , Milligan Gary , Moon Rebecca
Published: March 2020

Background

Reductions in health-related quality of life (HRQoL) in patients with chronic kidney disease (CKD) are thought to be exacerbated by the low hemoglobin (Hb) levels that define anemia, a common complication of CKD. The current analysis evaluated the impact of anemia on HRQoL and work productivity in patients with non-dialysis dependent and dialysis-dependent CKD using real-world data.

Methods

Data were collected in France, Germany, Italy, Spain, the UK, the USA and China in 2012–2018 in the Adelphi Real World Disease Specific Programme™ for CKD, a large, cross-sectional, survey of physicians and their patients. Patients completed three patient-reported outcomes (PRO) instruments: the EuroQol 5-Dimension 3-level (EQ-5D-3 L), the Kidney Disease Quality of Life (KDQOL-36) instrument and the Work Productivity and Activity Impairment questionnaire. PROs were assessed by CKD stage and Hb levels, and regression analyses were performed with CKD stage and Hb level as independent variables and PROs as outcome variables, while adjusting for age, sex, CKD stage, comorbidities and cardiovascular risk.

Results

Overall, 5276 patients participated in the survey, including 28% stage 4 and 36% dialysis patients. Patients with lower Hb levels more often reported problems/issues on all EQ-5D-3 L domains (p < 0.0001). Regression analyses showed significant associations between lower Hb levels and the probability of low (< 0.8) EQ-5D-3 L utility scores (p < 0.0001) and low visual analog scale scores (p < 0.05), indicating poorer health status. Associations were seen even when adjusting for CKD stage and other potential confounding factors. Significant associations were observed between Hb level and the 12-Item Short-Form Health Survey (SF-12) Physical Component Summary, SF-12 Mental Component Summary and the three KDQOL-36 subscales (all p < 0.0001), and were confirmed using linear regression analyses adjusting for CKD stage and other potential confounders. Numerically greater work productivity losses and greater activity impairment were observed with lower Hb levels.

Conclusions

Lower Hb levels worsen the impact of CKD on HRQoL, and are associated with lower work productivity in patients with CKD. Assessment and treatment of anemia should be recognized as a key component of integral CKD management throughout all stages of the disease.
Identifying children exposed to maltreatment: a systematic review update
Authors: McTavish Jill R. , Gonzalez Andrea , Santesso Nancy , MacGregor Jennifer C. D. , McKee Chris , MacMillan Harriet L.
Published: March 2020

Background

Child maltreatment affects a significant number of children globally. Strategies have been developed to identify children suspected of having been exposed to maltreatment with the aim of reducing further maltreatment and impairment. This systematic review evaluates the accuracy of strategies for identifying children exposed to maltreatment.

Methods

We conducted a systematic search of seven databases: Medline, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Cochrane Libraries, Sociological Abstracts and the Education Resources Information Center. We included studies published from 1961 to July 2, 2019 estimating the accuracy of instruments for identifying potential maltreatment of children, including neglect, physical abuse, emotional abuse, and sexual abuse. We extracted data about accuracy and narratively synthesised the evidence. For five studies—where the population and setting matched known prevalence estimates in an emergency department setting—we calculated false positives and negatives. We assessed risk of bias using QUADAS-2.

Results

We included 32 articles (representing 31 studies) that evaluated various identification strategies, including three screening tools (SPUTOVAMO checklist, Escape instrument, and a 6-item screening questionnaire for child sex trafficking). No studies evaluated the effects of identification strategies on important outcomes for children. All studies were rated as having serious risk of bias (often because of verification bias). The findings suggest that use of the SPUTOVAMO and Escape screening tools at the population level (per 100,000) would result in hundreds of children being missed and thousands of children being over identified.

Conclusions

There is low to very low certainty evidence that the use of screening tools may result in high numbers of children being falsely suspected or missed. These harms may outweigh the potential benefits of using such tools in practice (PROSPERO 2016:CRD42016039659).
The effects of testosterone on bone health in males with testosterone deficiency: a systematic review and meta-analysis
Authors: Zhang Zhichao , Kang Deying , Li Hongjun
Published: March 2020

Background

Testosterone deficiency (TD) may induce a series of clinical symptoms.

Studies have shown that testosterone supplementation may prevent these unfavourable symptoms and improve patients’ quality of life. Given the conflicting findings across studies, this systematic review aims to evaluate the effects and risks associated with testosterone supplementation in middle-aged or aging males with TD.

Methods

Electronic databases (MEDLINE, EMBASE, PubMed, and Cochrane.

Library were searched to December 2019. The risk of bias of individual included studies and the quality of the aggregate evidence were assessed using the GRADE approach. Our primary outcome was bone mineral density (BMD). Meta-analyses were performed. This systematic review was reported according to the PRISMA statement.

Results

A total of 52 randomized controlled trials (RCTs) were included. When compared with placebo, testosterone supplementation did not increase total BMD (short-term: 1081 participants, MD − 0.01 g/cm2, 95% CI − 0.02 g/cm2to 0.01 g/cm2; long-term: 156 participants, MD 0.04 g/cm2, 95% CI − 0.07 g/cm2to 0.14 g/cm2), lumbar spine, hip, or femur neck BMD. Furthermore, testosterone supplementation did not decrease the risk of falling or fracture. Lastly, it was found that testosterone supplementation did not increase the risk of cardiovascular events (1374 participants, RR 1.28, 95% CI 0.62 to 2.64), all-cause mortality (729 participants, RR 0.55, 95% CI 0.29 to 1.04), or prostatic events. However, testosterone supplementation may improve sexual function and quality of life (1328 participants, MD -1.32, 95% CI − 2.11 to − 0.52).

Conclusions

The effect of testosterone supplementation on BMD and the risk of falls or fracture remains inconclusive. However, supplementation may benefit patients in the areas of sexual function and quality of life without increasing the risk of cardiovascular events, all-cause mortality, or prostatic events. RCTs with a longer follow-up period are still required.

Trial registration

We registered our protocol in PROSPERO (CRD42018109738).
RETRACTED ARTICLE: A novel positive feedback loop of linc02042 and c-Myc mediated by YBX1 promotes tumorigenesis and metastasis in esophageal squamous cell carcinoma
Authors: Du Jiahui , Zhang Guangzhao , Qiu Hongli , Yu Haifeng , Yuan Wuying
Published: March 2020

Background

Long non-coding RNA (lncRNA) is a class of endogenous RNA with a length of more than 200 nucleotides, which is emerging as a pivotal player in cancer development and progression. However, the functional roles of many members in this class remain largely uncharacterized. In the present study, we explored the biological relevance of linc02042 in esophageal squamous cell carcinoma (ESCC).

Methods

qRT-PCR was used to detect the levels of linc02042 and c-Myc. Western blot was used to assess protein expression level. CCK-8 and Transwell assays were employed to test ESCC cell proliferation and invasion, respectively. The mice study including xenograft tumor and lung metastasis models was used to determine the role of linc02042 in vivo. RNA pull-down, ChIP and luciferase reporter assays were employed to test the relationship between linc02042, YBX1 and c-Myc.

Results

Linc02042 was found to be markedly upregulated in ESCC cell lines, tissues and plasma, and was closely correlated with malignant clinical features. Knockdown of linc02042 significantly inhibited ESCC cell viability and invasion in vitro as well as tumor growth and lung metastasis in vivo, whereas overexpression of linc02042 resulted in the opposite results. Mechanistically, linc02042 acted as a scaffold for YBX-1 binding to the 3′-UTR of c-Myc mRNA, leading to enhanced c-Myc mRNA stability, thereby facilitating ESCC growth and metastasis. Moreover, in turn, c-Myc was able to transcriptionally elevate linc02042 by directly binding to the E-box motif proximal to the transcription start site (TSS) of linc02042 promoter. Clinically, linc02042 was identified as an effective diagnostic and prognostic biomarker for ESCC patients, and its expression was strongly positively correlated with c-Myc expression in ESCC tissues.

Conclusion

Our data suggest that linc02042 plays an important tumor-promoting role in ESCC, which lays a foundation for considering it as a potential target for ESCC patients.
Screening and identification of MicroRNAs expressed in perirenal adipose tissue during rabbit growth
Authors: Wang Guoze , Guo Guo , Tian Xueting , Hu Shenqiang , Du Kun , Zhang Qinghai , Mao Jingxin , Jia Xianbo , Chen Shiyi , Wang Jie , Lai Songjia
Published: March 2020

Background

MicroRNAs (miRNAs) regulate adipose tissue development, which are closely related to subcutaneous and intramuscular fat deposition and adipocyte differentiation. As an important economic and agricultural animal, rabbits have low adipose tissue deposition and are an ideal model to study adipose regulation. However, the miRNAs related to fat deposition during the growth and development of rabbits are poorly defined.

Methods

In this study, miRNA-sequencing and bioinformatics analyses were used to profile the miRNAs in rabbit perirenal adipose tissue at 35, 85 and 120 days post-birth. Differentially expressed (DE) miRNAs between different stages were identified by DEseq in R. Target genes of DE miRNAs were predicted by TargetScan and miRanda. To explore the functions of identified miRNAs, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed.

Results

Approximately 1.6 GB of data was obtained by miRNA-seq. A total of 987 miRNAs (780 known and 207 newly predicted) and 174 DE miRNAs were identified. The miRNAs ranged from 18 nt to 26 nt. GO enrichment and KEGG pathway analyses revealed that the target genes of the DE miRNAs were mainly involved in zinc ion binding, regulation of cell growth, MAPK signaling pathway, and other adipose hypertrophy-related pathways. Six DE miRNAs were randomly selected, and their expression profiles were validated by q-PCR.

Conclusions

This is the first report of the miRNA profiles of adipose tissue during different growth stages of rabbits. Our data provide a theoretical reference for subsequent studies on rabbit genetics, breeding and the regulatory mechanisms of adipose development.
Autonomic nervous system and inflammation interaction in endometriosis-associated pain
Authors: Wei Yajing , Liang Yanchun , Lin Haishan , Dai Yujing , Yao Shuzhong
Published: March 2020

Endometriosis is a chronic inflammatory disease. Pain is the most common symptom in endometriosis. Endometriosis-associated pain is caused by inflammation, and is related to aberrant innervation. Although the specific mechanism between endometriosis-associated pain and the interaction of aberrant innervation and inflammation remains unclear, many studies have confirmed certain correlations between them. In addition, we found that some chronic inflammatory autoimmune diseases (AIDs) such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) share similar characteristics: the changes in dysregulation of inflammatory factors as well as the function and innervation of the autonomic nervous system (ANS). The mechanisms underlying the interaction between the ANS and inflammation have provided new advances among these disorders. Therefore, the purpose of this review is to compare the changes in inflammation and ANS in endometriosis, IBD, and RA; and to explore the role and possible mechanism of sympathetic and parasympathetic nerves in endometriosis-associated inflammation by referring to IBD and RA studies to provide some reference for further endometriosis research and treatment.
Active learning with point supervision for cost-effective panicle detection in cereal crops
Authors: Chandra Akshay L. , Desai Sai Vikas , Balasubramanian Vineeth N. , Ninomiya Seishi , Guo Wei
Published: March 2020

Background

Panicle density of cereal crops such as wheat and sorghum is one of the main components for plant breeders and agronomists in understanding the yield of their crops. To phenotype the panicle density effectively, researchers agree there is a significant need for computer vision-based object detection techniques. Especially in recent times, research in deep learning-based object detection shows promising results in various agricultural studies. However, training such systems usually requires a lot of bounding-box labeled data. Since crops vary by both environmental and genetic conditions, acquisition of huge amount of labeled image datasets for each crop is expensive and time-consuming. Thus, to catalyze the widespread usage of automatic object detection for crop phenotyping, a cost-effective method to develop such automated systems is essential.

Results

We propose a point supervision based active learning approach for panicle detection in cereal crops. In our approach, the model constantly interacts with a human annotator by iteratively querying the labels for only the most informative images, as opposed to all images in a dataset. Our query method is specifically designed for cereal crops which usually tend to have panicles with low variance in appearance. Our method reduces labeling costs by intelligently leveraging low-cost weak labels (object centers) for picking the most informative images for which strong labels (bounding boxes) are required. We show promising results on two publicly available cereal crop datasets—Sorghum and Wheat. On Sorghum, 6 variants of our proposed method outperform the best baseline method with more than 55% savings in labeling time. Similarly, on Wheat, 3 variants of our proposed methods outperform the best baseline method with more than 50% of savings in labeling time.

Conclusion

We proposed a cost effective method to train reliable panicle detectors for cereal crops. A low cost panicle detection method for cereal crops is highly beneficial to both breeders and agronomists. Plant breeders can obtain quick crop yield estimates to make important crop management decisions. Similarly, obtaining real time visual crop analysis is valuable for researchers to analyze the crop’s response to various experimental conditions.
Is the HERV-K HML-2 Xq21.33, an endogenous retrovirus mutated by gene conversion of chromosome X in a subset of African populations, associated with human breast cancer?
Authors: Kaplan Mark H. , Contreras-Galindo Rafael , Jiagge Evelyn , Merajver Sofia D. , Newman Lisa , Bigman Galya , Dosik Michael H. , Palapattu Ganesh S. , Siddiqui Javed , Chinnaiyan Arul M. , Adebamowo Sally , Adebamowo Clement
Published: March 2020

The human endogenous retroviruses HERV-K HML-2 have been considered a possible cause of human breast cancer (BrC). A HERV-K HML-2 fully intact provirus Xq21.33 was recently identified in some West African people. We used PCR technology to search for the Xq21.33 provirus in DNA from Nigerian women with BrC and controls. to see if Xq21.33 plays any role in predisposing to BrC. This provirus was detected in 27 of 216 (12.5%) women with BrC and in 22 of 219 (10.0%) controls. These results were not statistically significant. The prevalence of provirus in premenopausal control women 44 years or younger [18/157 (11.46%)} vs women with BrC [12/117 (10.26%)] showed no statistical difference. The prevalence of virus in postmenopausal control women > 45 yrs. was 7.4% (4/54) vs 15.31% (15/98) in postmenopausal women with BrC. These changes were not statistically significant at <.05, but the actual p value of <.0.079, suggests that Xq21.33 might play some role in predisposing to BrC in postmenopausal women. Provirus was present in Ghanaian women (6/87), in 1/6 Pygmy populations and in African American men (4/45) and women (6/68), but not in any Caucasian women (0/109). Two BrC cell lines (HCC 70 and DT22) from African American women had Xq21.33. Env regions of the virus which differed by 2–3 SNPs did not alter the protein sequence of the virus. SNP at 5730 and 8529 were seen in all persons with provirus, while 54% had an additional SNP at 7596.Two Nigerian women and 2 Ghanaian women had additional unusual SNPs. Homozygosity was seen in (5/27) BrC and (2/22) control women. The genetic variation and homozygosity patterns suggested that there was gene conversion of this X chromosome associated virus. The suggestive finding in this preliminary data of possible increased prevalence of Xq21.33 provirus in post-menopausal Nigerian women with BrC should be clarified by a more statistically powered study sample to see if postmenopausal African and/or African American women carriers of Xq21.33 might show increased risk of BrC. The implication of finding such a link would be the development of antiretroviral drugs that might aid in preventing BrC in Xq21.33+ women.
A rare CACNA1H variant associated with amyotrophic lateral sclerosis causes complete loss of Cav3.2 T-type channel activity
Authors: Stringer Robin N. , Jurkovicova-Tarabova Bohumila , Huang Sun , Haji-Ghassemi Omid , Idoux Romane , Liashenko Anna , Souza Ivana A. , Rzhepetskyy Yuriy , Lacinova Lubica , Van Petegem Filip , Zamponi Gerald W. , Pamphlett Roger , Weiss Norbert
Published: March 2020

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of cortical, brain stem and spinal motor neurons that leads to muscle weakness and death. A previous study implicated CACNA1H encoding for Cav3.2 calcium channels as a susceptibility gene in ALS. In the present study, two heterozygous CACNA1H variants were identified by whole genome sequencing in a small cohort of ALS patients. These variants were functionally characterized using patch clamp electrophysiology, biochemistry assays, and molecular modeling. A previously unreported c.454GTAC > G variant produced an inframe deletion of a highly conserved isoleucine residue in Cav3.2 (p.ΔI153) and caused a complete loss-of-function of the channel, with an additional dominant-negative effect on the wild-type channel when expressed in trans. In contrast, the c.3629C > T variant caused a missense substitution of a proline with a leucine (p.P1210L) and produced a comparatively mild alteration of Cav3.2 channel activity. The newly identified ΔI153 variant is the first to be reported to cause a complete loss of Cav3.2 channel function. These findings add to the notion that loss-of-function of Cav3.2 channels associated with rare CACNA1H variants may be risk factors in the complex etiology of ALS.
Antioxidant defense in the eyes of immunocompetent and immunosuppressed mice infected with Acanthamoeba spp.
Authors: Kot Karolina , Kosik-Bogacka Danuta , Kupnicka Patrycja , Łanocha-Arendarczyk Natalia
Published: March 2020

Background

Acanthamoebaspp. are ubiquitous pathogens which cause granulomatous amoebic encephalitis and disseminated infection. Moreover,Acanthamoebaspp. infection of the cornea leads toAcanthamoebakeratitis. Our previous study showed that the infection of an eyeball may also take placeviathe migration of trophozoites through the optic nerve from the brain to the eyes. The aim of the study was to analyze the activity of enzymatic antioxidants and the concentration of non-enzymatic antioxidant in the eyes of immunocompetent and immunocompromised mice with disseminated acanthamoebiasis.

Results

In the immunocompetent mice infected withAcanthamoebaspp. we noted a significant decrease in catalase activity at 8 and 16 days post-infection (dpi). Glutathione reductase activity was significantly lower at 16 dpi compared to the control group and glutathione concentration was statistically higher at 24 dpi than in the control group. In the immunosuppressed mice, a statistically significant increase in glutathione concentration in the eye samples was found at 16 dpi compared to those not infected withAcanthamoebaspp. In the immunosuppressed mice infected withAcanthamoebaspp., glutathione peroxidase activity was statistically lower at 8 dpi, and glutathione concentration was statistically significantly higher at 16 dpi compared to the control group.

Conclusions

The inflammatory response in the eyes of hosts with experimental acanthamoebiasis led to changes in the activity of enzymatic antioxidants and the content of non-enzymatic antioxidant. Therefore, the dysregulation of antioxidants may play a role in the pathomechanism ofAcanthamoebaeye infection.
Immunophenotyping of the PD-L1-positive cells in angioimmunoblastic T cell lymphoma and Hodgkin disease
Authors: Tiemann Markus , Samoilova Vera , Atiakshin Dmitri , Buchwalow Igor
Published: March 2020

Objective

Programmed death-1 (PD-1) and its ligand PD-L1 are now used as predictive biomarkers to guide clinical decisions. Precise characterization of PD-L1-positive cells may contribute to our knowledge of which patients derive benefit from the PD-L1 blockade therapy.

Results

To address this issue, we performed immunophenotyping of PD-L1-positive cells in Hodgkin lymphoma and in angioimmunoblastic T cell lymphoma (AITL) employing multiple immunofluorescent immunolabeling. We found that PD-L1-positive cells and PD-1-positive cells both in Hodgkin lymphoma and in AITL belong to two completely different cell lineages. In both lymphomas, PD-1 was found exclusively in T-lymphocytes, whereas PD-L1 was revealed in the tumor microenvironment cells including macrophages. PD-L1 was also detected in CD30-positive cells in Hodgkin lymphoma but not in AITL. The marker of B-cell lineage, CD20, was not detectable in PD-L1-positive cells both in AITL and in Hodgkin. Our study highlights the importance of comprehensive assessment of PD-1/PD-L1 regulatory pathways for employing PD-L1 as a predictive biomarker in clinical practice. PD-L1-antibody therapy is proven in Hodgkin lymphoma. Comparative immunophenotyping of the PD-1/PD-L1 axis provides a support for attempts to prove this principle also for AITL.
The proangiogenic effects of extracellular vesicles secreted by dental pulp stem cells derived from periodontally compromised teeth
Authors: Zhou Huan , Li Xuan , Yin Yuan , He Xiao-Tao , An Ying , Tian Bei-Min , Hong Yong-Long , Wu Li-An , Chen Fa-Ming
Published: March 2020

Background

Although dental pulp stem cells (DPSCs) isolated from periodontally compromised teeth (P-DPSCs) have been demonstrated to retain pluripotency and regenerative potential, their use as therapeutics remains largely unexplored. In this study, we investigated the proangiogenic effects of extracellular vesicles (EVs) secreted by P-DPSCs using in vitro and in vivo testing models.

Methods

Patient-matched DPSCs derived from periodontally healthy teeth (H-DPSCs) were used as the control for P-DPSCs. Conditioned media (CMs) derived from H-DPSCs and P-DPSCs (H-CM and P-CM), CMs derived from both cell types pretreated with the EV secretion blocker GW4869 (H-GW and P-GW), and EVs secreted by H-DPSCs and P-DPSCs (H-EVs and P-EVs) were prepared to test their proangiogenic effects on endothelial cells (ECs). Cell proliferation, migration, and tube formation were assessed using the Cell Counting Kit-8 (CCK-8), transwell/scratch wound healing, and Matrigel assays, respectively. Specifically, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blot analysis were used to examine the expression levels of angiogenesis-related genes/proteins in ECs in response to EV-based incubation. Finally, a full-thickness skin defect model was applied to test the effects of EVs on wound healing and new vessel formation.

Results

Both H-CM and P-CM promoted EC angiogenesis, but the proangiogenic effects were compromised when ECs were incubated in H-GW and P-GW, wherein the EV secretion was blocked by pretreatment with GW4869. In EV-based incubations, although both H-EVs and P-EVs were found to enhance the angiogenesis-related activities of ECs, P-EVs exerted a more robust potential to stimulate EC proliferation, migration, and tube formation. In addition, P-EVs led to higher expression levels of angiogenesis-related genes/proteins in ECs than H-EVs. Similarly, both P-EVs and H-EVs were found to accelerate wound healing and promote vascularization across skin defects in mice, but wounds treated with P-EVs resulted in a quicker healing outcome and enhanced new vessel formation.

Conclusions

The findings of the present study provide additional evidence that P-DPSCs derived from periodontally diseased teeth represent a potential source of cells for research and therapeutic use. Particularly, the proangiogenic effects of P-EVs suggest that P-DPSCs may be used to promote new vessel formation in cellular therapy and regenerative medicine.
Obesity: sex and sympathetics
Authors: Shi Zhigang , Wong Jennifer , Brooks Virginia L.
Published: March 2020

Obesity increases sympathetic nerve activity (SNA) in men, but not women. Here, we review current evidence suggesting that sexually dimorphic sympathoexcitatory responses to leptin and insulin may contribute. More specifically, while insulin increases SNA similarly in lean males and females, this response is markedly amplified in obese males, but is abolished in obese females. In lean female rats, leptin increases a subset of sympathetic nerves only during the high estrogen proestrus reproductive phase; thus, in obese females, because reproductive cycling can become impaired, the sporadic nature of leptin-induced sympathoexcitaton could minimize its action, despite elevated leptin levels. In contrast, in males, obesity preserves or enhances the central sympathoexcitatory response to leptin, and current evidence favors leptin’s contribution to the well-established increases in SNA induced by obesity in men. Leptin and insulin increase SNA via receptor binding in the hypothalamic arcuate nucleus and a neuropathway that includes arcuate neuropeptide Y (NPY) and proopiomelanocortin (POMC) projections to the paraventricular nucleus. These metabolic hormones normally suppress sympathoinhibitory NPY neurons and activate sympathoexcitatory POMC neurons. However, obesity appears to alter the ongoing activity and responsiveness of arcuate NPY and POMC neurons in a sexually dimorphic way, such that SNA increases in males but not females. We propose hypotheses to explain these sex differences and suggest areas of future research.
Biosynthesis of uniformly carbon isotope-labeled docosahexaenoic acid in Crypthecodinium cohnii
Authors: Song Pingping , Kuryatov Alexander , Axelsen Paul H.
Published: March 2020

Docosahexaenoic acid (DHA) enriched in brain can yield many important degradation products after the attack of hydroxyl radicals, which is known to serve as a nutraceutical and neuroprotective effects. Oxidative stress is a commonly observed feature of Alzheimer’s disease (AD). Therefore, uniformly radiolabeled DHA plays an important role in studying the oxidative fate of DHA in vivo and vitro. However, carbon isotope labeled DHA isn’t commercially available now. The heterotrophic microalgae Crypthecodinium cohnii (C. cohnii) has been identified as a prolific producer of DHA. In this study, the growth rate and DHA production in C. cohnii were optimized in a new defined media, and the biosynthesis of U-13C-DHA from U-13C-glucose and U-14C-DHA from U-14C-glucose were analyzed by HPLC–MS/MS. Approximately 40 nmoles of U-13C-DHA with higher isotopic purity of 96.8% was produced in a 300 μL batch, and ~ 0.23 μCi of U-14C-DHA with significant specific activity of 5–6 Ci/mol was produced in a 300 μL batch. It was found that C. cohnii had the optimal growth and DHA accumulation at 25 °C in this defined media (C/N = 10). An efficient protocol for the biosynthesis of U-13C-DHA and U-14C-DHA were set up firstly, which provides the basic support for the analysis of oxidative degradation products of DHA in AD.
Serum IP-10 and IL-17 from Kawasaki disease patients induce calcification-related genes and proteins in human coronary artery smooth muscle cells in vitro
Authors: Chang Shun-Fu , Liu Shih-Feng , Chen Cheng-Nan , Kuo Ho-Chang
Published: March 2020

Background

Kawasaki disease (KD) is one of the major causes of heart disease and vasculitis in children under 5 years old in the world. Clinical evidence has shown that coronary artery calcification may develop in KD patients, however the mechanism has not been elucidated. Previous studies have found that interferon-γ-inducible protein (IP)-10 and interleukin (IL)-17 can be elevated and may play a role in KD development and coronary artery lesion formation. The purpose of this in vitro study was to investigate the possible role of plasma circulating IP-10 and IL-17 of KD patients in vascular calcification development and its underlying mechanism.

Result

Human coronary artery smooth muscle cells (HCASMCs) were used in this study. We found that HCASMCs treated with IP-10/IL-17-containing KD serum and co-treated with IP-10/IL-17 recombinant proteins could induce a phenotype that may promote vascular calcification by the bone morphogenetic protein (BMP) 6 autocrine effect. Moreover, the BMP6 autocrine stimulation in IP-10/IL-17 co-treated HCASMCs could upregulate the smad1/5-runx2 signaling activation, thus increasing the expression of bone matrix-related proteins, i.e., osteopontin, osteocalcin, and alkaline phosphatase.

Conclusions

The presented in vitro results provided new insights into the comprehension of the pathogenesis of vascular calcification in SMCs in KD progression. Although additional in vivo experimental models should be completed to confirm the in vivo relevance of these in vitro findings, the results related to the autocrine role of BMP6 may provide a new direction for theranostic drug development to treat KD.
Anteromedial positioning of the femoral tunnel in anterior cruciate ligament reconstruction is the best option to avoid revision: a single surgeon registry
Authors: de Paula Leite Cury Ricardo , Simabukuro Artur Mistieri , de Marques Oliveira Victor , Escudeiro Diego , Jorge Pedro Baches , Severino Fabrício Roberto , Guglielmetti Luiz Gabriel Betoni
Published: March 2020

Purpose

The aim of the study is to compare the risk of revision of single-bundle hamstring anterior cruciate ligament (ACL) reconstruction between the anteromedial, transtibial and outside-in techniques.

Methods

This cohort study was based on data from a single surgeon’s registry. Patients who underwent primary single-bundle ACL reconstruction with hamstring tendon using the anteromedial portal, transtibial and outside-in technique, operated between 1 November 2003 to 31 December 2016, were eligible for inclusion. A minimum follow-up of 2 years was used, and the end-point of the study was revision surgery.

Results

The total number of registered surgeries identified was 665; 109 were excluded, and 556 was the final sample. The overall revision rate was 8.7%. The transtibial technique presented 14/154 [9.9%] of revisions, the transportal 11/96 [11.4%] and the outside-in 22/306 [7.2%]. Separating the outside-in group into central outside-in and anteromedial (AM) outside-in, 18/219 [8.2%] was found for the central outside-in and 4/87 [4.5%] for the AM outside-in technique. Statistical evaluation of the first comparison (transtibial vs. transportal vs. outside-in) obtained p = (n.s.) The second comparison (transtibial vs. central transportal vs. central outside-in vs. AM outside-in, p = (n.s). Placement was also evaluated: high anteromedial placement (transtibial) vs. central (transportal and central outside-in technique) vs. AM placement (AM outside-in). The high AM placement presented 14/154 [9.9%] of revision, the central placement 29/315 [9.2%] and the AM placement 4/87 [4.5%], p = (n.s.) The AM placement was also compared with the other placements (high and central AM), p = (n.s.)

Conclusion

Based on the registry of a single surgeon during 14 years of ACL reconstruction, the placement of the femoral tunnel in the high anteromedial region was associated with a rupture rate of 9.9%, central placement with 9.2% and anteromedial placement with 4.5%.
Indicators of male fertility potential in adult patients with beta-thalassemia major: a comparative study between patients undergone allogeneic stem cell transplantation and transfusion-dependent patients
Authors: Rostami Tahereh , Mohammadifard Mohammad Amir , Ansari Shahla , Kiumarsi Azadeh , Maleki Nasrollah , Kasaeian Amir , Aghamahdi Fatemeh , Rad Soroush , Ghavamzadeh Ardeshir
Published: March 2020

Background

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment for thalassemia major (TM). Infertility and its indicators have been assessed in transfusion dependent TM men, but in this study, we sought to compare the fertility indicators of TM patients after HSCT with those in patients treated conventionally. The possible influential factors on reproductive capacity in TM patients undergone allogeneic HSCT were also evaluated.

Patients and methods

In this cross-sectional study, we compared the gonadal hormones level, testicular volume, Tanner stage and sperm analysis in transfusion-dependent thalassemia major (TDTM) patients who survived matched sibling HSCT (n = 43) with patients conventionally treated by transfusion and iron chelation (n = 52).

Results

The patients’ age range was between 16 to 41 years. Tanner stage 4–5 was seen in 39 patients (41%). The prevalence of hypogonadism in our patients was 32.63% but its frequency was not significantly different between the two groups (p = 0.35). Azospermia, oligospermia, astenospermia, teratospermia and even having dry and low volume ejaculate were all significantly more frequent in the post-transplant patients compared to TDTM group. In the post-HSCT group, neither patients’ age at transplantation nor the conditioning regimen used in their transplant process did significantly affect their hormonal status and sperm parameters. Chronic graft versus host disease (GVHD) occurred in 14 (40%) patients. No significant difference was observed between the grade of chronic GVHD and hypogonadism (P = 0.853).

Conclusions

Thalassemia patients undergone allogeneic HSCT have lower fertility potential, mainly in sperm parameters compared with patients treated with blood transfusion and chelation. This information is important for thalassemic patients considering HSCT.
Multiple heterochronic gastrointestinal stromal tumors in the stomach detected 6 years after resection: a case report
Authors: Yasuda Tadahito , Eto Kojiro , Yoshida Naoya , Iwagami Shiro , Hiyoshi Yukiharu , Nagai Youhei , Iwatsuki Masaaki , Ishimoto Takatsugu , Baba Yoshifumi , Miyamoto Yuji , Shiota Takuya , Mikami Yoshiki , Baba Hideo
Published: March 2020

Background

To date, only a few cases of multiple GISTs with different clones in different organs have been published. However, a case of multiple GISTs with different clones occurring in a single organ has never been reported.

Case presentation

A 41-year-old patient underwent laparoscopic partial gastrectomy for gastric gastrointestinal stromal tumor (GIST) in 2012. The pathological findings showed high-risk characteristics for recurrence, so he received adjuvant therapy with imatinib for 3 years. In 2018, 3 years after completing the adjuvant therapy, tumor lesions at residual gastric cardia were incidentally identified by follow-up computed tomography (CT). The pathological findings of the tumor biopsy revealed gastric GIST. He underwent secondary laparoscopic partial gastrectomy and was diagnosed with high-risk GIST. Adjuvant therapy with imatinib was restarted immediately. The two gastric GISTs had the same exon 11 mutations in the c-kit gene, but they had different missense mutations. This molecular heterogeneity suggested that they were derived from different origins.

Conclusion

We reported a multiple heterochronic GIST in the stomach detected 6 years after resection. There may be a possibility that another heterochronic GIST will occur in the remnant stomach in the future, so close follow-up will be needed.
Relationships among weight stigma, eating behaviors and stress in adolescents in Wuhan, China
Authors: Wang Zhanxia , Wang Bowen , Hu Yiluan , Cheng Lei , Zhang Siqi , Chen Yanan , Li Rui
Published: March 2020

Background

The purpose of this study was to examine the relationships among weight stigma, eating behaviors, and stress, as well as to analyze the effect of stress in mediating the association between weight stigma and eating behaviors.

Methods

The study involved 1818 adolescents between 14 to 19 years of age and was conducted in Wuhan, China in 2019. Weight stigma, eating behaviors (cognitive restraint, uncontrolled eating, and emotional eating), and stress were assessed by self-report questionnaires. Hierarchical linear regression analyses were used to examine the predictors of cognitive restraint, uncontrolled eating, and emotional eating; the serial mediation models analyses were conducted to analyze the effect of stress in mediating the association between weight stigma and eating behaviors for the whole non-overweight (normal and underweight) and overweight or obese participants, respectively.

Results

Hierarchical linear regression analyses showed that experiences of weight stigma significantly predicted uncontrolled eating and emotional eating regardless of body mass index (BMI) (non-overweight adolescents: uncontrolled eating: β [SE] = 0.161 [0.017]; emotional eating: β [SE] = 0.199 [0.008], p < 0.05; overweight or obese adolescents: uncontrolled eating: β [SE] = 0.286 [0.030]; emotional eating: β [SE] = 0.267 [0.014], p < 0.05); experiences of weight stigma significantly predicted cognitive restraint among non-overweight adolescents (β [SE] = 0.204 [0.013], p < 0.05). Mediation analyses showed that stress mediated the associations between weight stigma and uncontrolled eating and emotional eating among non-overweight adolescents (uncontrolled eating: indirect effect coefficient = 0.0352, 95% CI = 0.0241, 0.0478; emotional eating: indirect effect coefficient = 0.0133, 95% CI = 0.0085, 0.0186).

Conclusions

These findings suggest that non-overweight individuals can still experience weight stigma and its associated negative consequences; the relationship between weight stigma and eating behaviors is modulated by weight status; stress mediated the associations between weight stigma and uncontrolled and emotional eating among non-overweight adolescents.
Antibiotic sensitivity and RAPD-PCR studies on cultivable gut bacteria from Indian Medicinal Leech—Hirudinaria granulosa
Authors: Patel Dhaval , Koriya Khushbu , Patel Pinkal , Solanki Jyoti , Mesara Suresh , Nataraj M.
Published: March 2020

Background

Hirudo granulosa—an Indian cattle leech, is frequently used for the treatment of psoriasis and eczema. During treatment which followed by leech biting, it transfers some amount of gut microbes along with saliva. This may result in bacterial infection at the treatment site. Antibiotics used as post-surgical hirudotherapy is the reason for drug resistance. Drug resistance is the result of the change in the genetic makeup of bacteria. Therefore, it is necessary to study antibiotic sensitivity of gut bacteria and characterized them genetically.

Results

Fourteen bacterial isolates were obtained from unused leech in which five were Gram-negative and the other nine were Gram-positive. Similarly from the used leech, thirteen were isolated in which five were Gram-negative and the other eight were Gram-positive. Biochemical analysis reveals that isolates from unused leech saliva belong to Pseudomonas, Micrococcus, Streptococcus, and Vibrio species, while the used leech salivary bacteria were the member of genus Pseudomonas, Comamonas, Escherichia, Citrobacter, Aeromonas, Providencia, Enterobacter, and Yersinia. Antibiotic sensitivity tests for isolates indicated that chloramphenicol (30 μg) and norfloxacin (10 μg) were effective for unused leech isolates while sparfloxacin (5 μg) and Cefaclor (30 μg) were effective against used leech salivary isolates. Random primer (OPL-14)-based random amplified polymorphic DNA (RAPD) fingerprint showed twenty amplified regions among all tested bacteria. Most of the bacteria contain the tested sequence except U2, T2, T9A, and T10 which showed no amplification indicated the absence of primers sequence.

Conclusion

Chloramphenicol, norfloxacin, sparfloxacin, and Cefaclor antibiotics alone or in combination were possibly used to treat post-therapy infections. Bacteria from treated and untreated leeches were clustered at nearby branch in neighbor end-joining phylogenetic tree, which indicates the similar (but not exact) genetic makeup. Therefore, it can be concluded that these antibiotics were possibly used against most of them.
Phase Ib/II study of INNO-206 (EMCH-doxorubicin) in patients with soft tissue sarcoma.
Authors: Chawla Sant P. , Chua Victoria S , Hendifar Andrew , Quon Doris , Nagre Sandeep , Ganjoo Kristen N. , Sankhala Kamalesh , Wieland Scott , Levitt Daniel
Published: March 2020

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Background: The safety and preliminary tumor response of a doxorubicin conjugate, INNO-206, was evaluated primarily in patients with metastatic STS who progressed on prior chemotherpy. INNO-206 consists of doxorubicin attached to an acid-sensitive linker that binds covalently to cysteine-34 in circulating albumin. Methods: INNO-206 was administered IV at doses of either 230, 350 and 450 mg/m2 (165, 260 and 325 mg/m2 dox. eq.) every 21 days for up to 8 consecutive cycles. Subsequent dose levels were administered if < 2/5 or 4/8 patients experienced a non-hematological dose-limiting toxicity during Cycle 1. Tumor response was monitored every other month and treatment continued until tumor progression or unacceptable toxicity. Standard safety monitoring was performed and cardiac function was followed periodically using MUGA or cardiac ultrasound. Results: As of January 11, 2012, 25 patients were entered in the study. 21/25 patients had STS of various types. Of the 5 patients treated at 230 mg/m2 INNO-206, 1 subject had grade 3 fatigue and acid reflux. Of the initial 5 patients entered at the 350 mg/m2 dose, no individuals experienced a grade 3 or 4 non-hematological toxicity during cycle 1. 2 patients treated at the 450 mg/m2 dose developed grade 3 oral mucositis during cycle 1. No patient exhibited cardiotoxicity as determined by MUGA or cardiac ultrasound. The MTD was determined to be 350 mg/m2 INNO-206 (260 mg/m2 dox.eq.). 15 more patients were entered at this dose (total of 20 patients). Of the 16 patients with STS, 3 objective partial responses (one of whom received prior doxorubicin) are ongoing as well as 10 patients with stable disease (range 2-7 months). 1 patient had progressive disease at the first evaluation. 2 patients died within the first cycle, one due to progressive disease and the other due to sepsis. Conclusions: INNO-206 is an active drug for the treatment of patients with advanced STS who have failed prior chemotherapy. Cumulative doses of 2000 mg/m2 of doxorubicin equivalents have been achieved, which is over 3 1/2 x the peak cumulative dose of standard doxorubicin. Adverse events are primarily hematological and no cardiotoxicity has been observed.