bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between alcohol intake and diabetic retinopathy risk: a systematic review and meta-analysis
Authors: Chen Chen , Sun Zhaojun , Xu Weigang , Tan Jun , Li Dan , Wu Yiting , Zheng Ting , Peng Derong
Published: July 2020

Background

Some previous studies have reported inconsistent results on the association between alcohol intake and diabetic retinopathy (DR) risk. This study aimed to evaluate the potential effects of alcohol intake on subsequent DR risk using a meta-analytic approach.

Methods

Three electronic databases (PubMed, EmBase, and the Cochrane library) were systematically searched for observational studies from their inception till November 2019. The pooled odds ratio (OR) with 95% confidence interval (CI) were applied for the summary effect estimate using a random-effects model.

Results

A total of 15 studies (5 cohort studies, 4 case-control studies, and 6 cross-sectional studies) with 37,290 participants and 12,711 DR cases were selected for the final meta-analysis. The pooled OR indicated no significant association between alcohol intake and DR risk (OR: 0.91; 95%CI: 0.78–1.06;P = 0.225), irrespective of the studies being pooled cohort (OR: 0.95; 95%CI: 0.66–1.36;P = 0.761), case-control (OR: 0.97; 95%CI: 0.77–1.23;P = 0.818), or cross-sectional (OR: 0.86; 95%CI: 0.69–1.08;P = 0.190) ones. However, this association might have been affected by the type of diabetes mellitus and the adjusted status.

Conclusion

The results of this study showed that the potential impact of alcohol intake on DR risk may differ according to the type of diabetes mellitus and adjusted status. Further large-scale, prospective cohort studies should be conducted to verify the findings of this study and to evaluate DR risk in relation to the dose and type of alcohol intake.
Quality of life and the prevalence of urinary incontinence after surgical treatment for gynecologic cancer: a questionnaire survey
Authors: Nakayama Noriko , Tsuji Tetsuya , Aoyama Makoto , Fujino Takafumi , Liu Meigen
Published: July 2020

Background

Although there have been a number of reports on urinary voiding symptoms associated with surgical interventions for gynecologic cancer and post-voiding symptoms, there have been few reports on urinary storage symptoms such as urinary incontinence (UI) and overactive bladder (OAB). The purpose of this study was to examine the rates and impact on quality of life (QOL) of urinary storage symptoms after gynecologic cancer surgery.

Methods

A questionnaire survey, including Japanese-language versions of the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), Overactive Bladder Symptom Score (OABSS), and Incontinence Impact Questionnaire-7 (IIQ-7), was distributed to gynecologic cancer patients who underwent hysterectomy between 2008 and 2013.

Results

Of the 145 patients analyzed, 49 (33.8%) had UI pre-surgery, and 76 (52.4%) had UI post-surgery, including 34 (35.4%) first-time UI patients, with a significant difference between pre- and post-surgery. Of the 49 subjects with UI pre-surgery, 43 (87.7%) had stress incontinence, while of the 76 patients with UI post-surgery, 44 (57.1%) had stress incontinence, and 24 (31.2%) had mixed incontinence. Seven (4.8%) subjects had OAB pre-surgery, whereas 19 (13.1%) had OAB symptoms post-surgery (including 15 first-time OAB patients), with a significant difference between pre- and post-surgery. IIQ-7 scores were markedly higher for patients with mixed incontinence post-surgery than for those with stress incontinence, indicating a lower QOL. Logistic regression analysis identified the number of Cesarean sections and days of urinary bladder catheterization as risk factors for postoperative UI.

Conclusions

UI and OAB rates were higher after gynecologic cancer surgery than in the general female population. The mixed incontinence rate was markedly higher post-surgery; QOL was low for such patients due to the combination of urge and stress incontinence. Multiple Cesarean sections and urinary bladder catheterization post-surgery were risk factors for post-surgical UI.
Implementing a community model of early pregnancy care
Authors: Cox Rebecca , Khalid Somia , Brierly Gemma , Forsyth Annie , McNamara Ruth , Heppell Victoria , Granne Ingrid
Published: July 2020

Background

In the UK Early Pregnancy Assessment Units (EPAUs) are usually situated alongside hospital maternity and gynaecology services. In June 2018, the Oxford EPAU relocated from the John Radcliffe Hospital to a community clinic. This is to our knowledge, the UK’s first community-based EPAU. This change was inspired by our patient feedback describing the co-location of the EPAU with maternity services as distressing.

Methods

Following the introduction of the community EPAU we developed a database to capture information on the patients seen in the clinic. This is a retrospective observational study of a single cohort of patients attending the clinic over an 8 month period. Data was collected from 1st July 2018 to 28th February 2019. This data included clinical, safety and patient experience outcomes.

Results

Two thousand nine hundred and twenty patient episodes were recorded, 1,932 were new patients. Mean waiting time to be seen in clinic was 1.3 days. When miscarriage was confirmed 48.6% chose conservative management, 19.9% chose medical management, and 31.5% chose surgical management. The mean rate of ambulance transfers to hospital was 3.1 per month. Of all patients seen in EPAU 32 had unplanned admissions, which accounted for 2.7% of all patients seen in EPAU. Patient feedback questionnaires have been consistently positive.

Conclusion

The development of a community EPAU has improved services to allow care closer to home in an environment separate from maternity care. Our data shows that a community EPAU can deliver timely, good quality patient care, is safe, and a service valued by patients. Further research is indicated to evaluate the cost-effectiveness of community EPAUs and the long term safety and effectiveness of care.
Optimized real-time fluorescence PCR assay for the detection of porcine Circovirus type 3 (PCV3)
Authors: Yuan Lin , Liu Yingyi , Chen Yana , Gu Xiaoxue , Dong Hao , Zhang Shuo , Han Tao , Zhou Zhi , Song Xiaohui , Wang Chuanbin
Published: July 2020

Background

Porcine circovirus type 3 (PCV3) has been an emerging porcine virus spread around the world. The conserved DNA sequence of PCV3 enabled good performance in molecular biological assays.

Result

In this study, we developed a real-time fluorescence PCR assay for the detection of PCV3. The conserved region within Capsid genome of PCV3 was selected for the design of primer pairs and probes. After optimizing, a primer pair and probe was screened, providing high sensitivity (10 copies/μL) and specificity (no cross reaction with other porcine viruses or common bacterium). In addition, this method was applied in the detection of 110 clinical samples, and the performance was compared with other previously reported PCR and real-time PCR methods. This method provided higher detection rate.

Conclusion

A real-time fluorescence PCR assay has been developed for the detection of PCV3, with high sensitivity and specificity, exhibiting good performance in detecting clinical samples.
Neurotoxicity of bupivacaine and liposome bupivacaine after sciatic nerve block in healthy and streptozotocin-induced diabetic mice
Authors: Markova Liljana , Umek Nejc , Horvat Simon , Hadžić Admir , Kuroda Max , Pintarič Tatjana Stopar , Mrak Vesna , Cvetko Erika
Published: July 2020

Background

Long-acting local anaesthetics (e.g. bupivacaine hydrochloride) or sustained-release formulations of bupivacaine (e.g. liposomal bupivacaine) may be neurotoxic when applied in the setting of diabetic neuropathy. The aim of the study was to assess neurotoxicity of bupivacaine and liposome bupivacaine in streptozotocin (STZ) - induced diabetic mice after sciatic nerve block. We used the reduction in fibre density and decreased myelination assessed by G-ratio (defined as axon diameter divided by large fibre diameter) as indicators of local anaesthetic neurotoxicity.

Results

Diabetic mice had higher plasma levels of glucose (P < 0.001) and significant differences in the tail flick and plantar test thermal latencies compared to healthy controls (P < 0.001). In both diabetic and nondiabetic mice, sciatic nerve block with 0.25% bupivacaine HCl resulted in a significantly greater G-ratio and an axon diameter compared to nerves treated with 1.3% liposome bupivacaine or saline (0.9% sodium chloride) (P < 0.01). Moreover, sciatic nerve block with 0.25% bupivacaine HCl resulted in lower fibre density and higher large fibre and axon diameters compared to the control (untreated) sciatic nerves in both STZ-induced diabetic (P < 0.05) and nondiabetic mice (P < 0.01). No evidence of acute or chronic inflammation was observed in any of the treatment groups.

Conclusions

In our exploratory study the sciatic nerve block with bupivacaine HCl (7 mg/kg), but not liposome bupivacaine (35 mg/kg) or saline, resulted in histomorphometric indices of neurotoxicity. Histologic findings were similar in diabetic and healthy control mice.
Several Plasmodium vivax relapses after correct primaquine treatment in a patient with impaired cytochrome P450 2D6 function
Authors: Martin Ramírez Alexandra , Lombardia González Carlos , Soler Maniega Tamara , Gutierrez Liarte Ángela , Domingo García Diego , Lanza Suárez Marta , Bernal Fernández María Josefa , Rubio José Miguel
Published: July 2020

Background

Plasmodium vivaxmalaria is characterized by the presence of dormant liver-stage parasites, called hypnozoites, which can cause malaria relapses after an initial attack. Primaquine, which targets liver hypnozoites, must be used in combination with a schizonticidal agent to get the radical cure. However, relapses can sometimes occur in spite of correct treatment, due to different factors such as a diminished metabolization of primaquine.

Case presentation

In January 2019, a 21 years old woman with residence in Madrid, returning from a trip to Venezuela with clinical symptoms compatible with malaria infection, was diagnosed with vivax malaria. Chloroquine for 3 days plus primaquine for 14 days was the elected treatment. Two months later and after a second trip to Venezuela, the patient presented a secondP. vivaxinfection, which was treated as the previous one. A thirdP. vivaxmalaria episode was diagnosed 2 months later, after returning from a trip to Morocco, receiving chloroquine for 3 days but increasing to 28 days the primaquine regimen, and with no more relapses after 6 months of follow up. The genotyping ofP. vivaxin the three malaria episodes revealed that the same strain was present in the different relapses. Upon confirmation of correct adherence to the treatment, non-description of resistance in the infection area and the highly unlikely re-infection on subsequent trips or stays in Spain, a possible metabolic failure was considered.CYP2D6encodes the human cytochrome P450 isoenzyme 2D6 (CYP2D6), responsible for primaquine activation. The patient was found to have aCYP2D6*4/*1 genotype, which turns out in an intermediate metabolizer phenotype, which has been related toP. vivaxrelapses.

Conclusions

The impairment in CYP2D6 enzyme could be the most likely cause ofP. vivaxrelapses in this patient. This highlights the importance of considering the analysis of CYP2D6 gene polymorphisms in cases ofP. vivaxrelapses after a correct treatment and, especially, it should be considered in any study of dosage and duration of primaquine treatment.
Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects
Authors: Li Chunxiao , Jiang Ping , Wei Shuhua , Xu Xiaofei , Wang Junjie
Published: July 2020

Regulatory T cells (Tregs) characterized by the expression of the master transcription factor forkhead box protein p3 (Foxp3) suppress anticancer immunity, thereby hindering protective immunosurveillance of tumours and hampering effective antitumour immune responses in tumour-bearing hosts, constitute a current research hotspot in the field. However, Tregs are also essential for the maintenance of the immune tolerance of the body and share many molecular signalling pathways with conventional T cells, including cytotoxic T cells, the primary mediators of tumour immunity. Hence, the inability to specifically target and neutralize Tregs in the tumour microenvironment without globally compromising self-tolerance poses a significant challenge. Here, we review recent advances in characterizing tumour-infiltrating Tregs with a focus on the functional roles of costimulatory and inhibitory receptors in Tregs, evaluate their potential as clinical targets, and systematically summarize their roles in potential treatment strategies. Also, we propose modalities to integrate our increasing knowledge on Tregs phenotype and function for the rational design of checkpoint inhibitor-based combination therapies. Finally, we propose possible treatment strategies that can be used to develop Treg-targeted therapies.
“Oil-soluble” reversed lipid nanoparticles for oral insulin delivery
Authors: Wang Tao , Shen Liao , Zhang Yadan , Li Haiyan , Wang Yongan , Quan Dongqin
Published: July 2020

Background

In this study, we aimed to design a novel oral insulin delivery system, named “oil-soluble” reversed lipid nanoparticles (ORLN), in which a hydrophilic insulin molecule is encapsulated by a phospholipid (PC) shell and dissolved in oil to prevent the enzymatic degradation of insulin. ORLN was characterized by transmission electron microscopy and dynamic light scattering.

Results

In vitro enzymatic stability studies showed higher concentrations of insulin in cells incubated with ORLN-encapsulated insulin than in those incubated with free insulin solution in artificial intestinal fluid (pH 6.5). The protective effect of ORLN was attributed to its special release behavior and the formulation of the PC shell and oil barrier. Furthermore, an in vivo oral efficacy study confirmed that blood glucose levels were markedly decreased after ORLN administration in both healthy and diabetic mice. In vivo pharmacokinetic results showed that the bioavailability of ORLN-conjugated insulin was approximately 28.7% relative to that of the group subcutaneously administered with an aqueous solution of insulin, indicating enhanced oral absorption.

Conclusions

In summary, the ORLN system developed here shows promise as a nanocarrier for improving the oral absorption of insulin.
Psychometric properties of the Japanese version of the Kansas City Cardiomyopathy Questionnaire in Japanese patients with chronic heart failure
Authors: Watanabe-Fujinuma Emi , Origasa Hideki , Bamber Luke , Roessig Lothar , Toyoda Tetsumi , Haga Yuri , Gwaltney Chad , Pieske Burkert
Published: July 2020

Background

Heart failure is a worldwide health problem that significantly affects patients’ physical function and health state. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific patient-reported outcome measure commonly used for the assessment of health states of patients with heart failure. This study aimed to evaluate the psychometric properties of the Japanese version of the KCCQ.

Methods

Using pooled data of 141 Japanese patients with chronic heart failure from three clinical trials, the Japanese version of the KCCQ was evaluated for validity and reliability, with a focus on the clinical summary score (CSS) and its component domains. For construct validity, the associations of baseline KCCQ scores with New York Heart Association (NYHA) class and the EuroQol five-dimension, three-level (EQ-5D-3L) scores at baseline were analyzed. For reliability, internal consistency was assessed using Cronbach’s α, and test–retest reliability (reproducibility) was assessed among stable patients. Responsiveness to changes in patients’ clinical status was assessed by analyzing score changes between two timepoints among patients whose health states improved.

Results

Among 141 patients (mean age, 73.7 ± 10.9 years), 76.6% were NYHA class II at baseline. For CSS and its component domains (physical limitations, symptom frequency, and symptom severity), baseline scores were all significantly lower in patients with a higher NYHA class (p <  0.001 for all, Jonckheere-Terpstra test). The physical limitations domain and CSS showed a moderate correlation (Spearman’s ρ = − 0.40 to − 0.54) with three functional status-related EQ-5D dimensions (mobility, self-care, and usual activities). The Cronbach’s standardized α was high (> 0.70) for all KCCQ domain/summary scores. In the test–retest analysis among 58 stable patients, all domain/summary scores minimally changed by 0.3–4.2 points with intraclass correlation coefficients of 0.65–0.84, demonstrating moderate to good reproducibility, except for the symptom stability domain. Among 44 patients with improved health states, all domain/summary scores except for the symptom stability and self-efficacy domains substantially improved from baseline with a medium to large effect size of 0.62–0.88.

Conclusions

The Japanese version of the KCCQ was demonstrated to be a valid and reliable tool for the assessment of symptoms and physical function of Japanese patients with chronic heart failure.
Outcomes from Indo–United States–Egypt tri-national psychiatric research training programmes
Authors: Malavia Tulsi A. , Nimgaonkar Vishwajit , Bhatia Triptish , Ibrahim Ibtihal M. A. , Mansour Hader , Wesesky Maribeth , Wood Joel , Deshpande Smita N. , Hawk Mary
Published: July 2020

Background

The prevalence of mental health disorders is increasing globally. Countries in South Asia, Southeast Asia and the Middle East regions carry high burdens of mental health need; however, there are relatively few mental health research publications from this region, suggesting inadequate research funds and a paucity of qualified research personnel. To increase and strengthen the pool of mental health researchers in India and Egypt, we conducted three psychiatric research programmes in these countries: the Training Program for Psychiatric Genetics in India (2002–2011), the Tri-National Training Program for Psychiatric Genetics (2009–2014) and the Cross-Fertilized Research Training for New Investigators in Egypt and India (2014–2019). A total of 66 trainees, including psychiatrists, psychiatric social workers, clinical psychologists and research psychologists, were supported in research development, which included didactic training, proposal development, hands-on research and manuscript preparation.

Methods

The aim of this study is to evaluate these three training programmes using the four-level Kirkpatrick Model of Training Evaluation that assesses reaction, learning, behaviour and outcomes. A descriptive analysis was used to explore the data collected throughout the duration of the three training programmes. Online surveys were crafted and sent to the mentors and trainees of the three programmes to supplement objective training data.

Results

In addition to positive changes in the areas of reaction, learning and behaviour, significant outcomes were demonstrated. As of the writing of this manuscript, the trainees published a total of 130 papers, 59 as first author. In addition, 26 trainees have co-authored papers with one or more trainees or mentors, which demonstrates successful research networking and collaboration.

Conclusion

Our findings suggest that our training approach is a successful model for building independent mental health researchers. This is a critical step in the development of effective mental health interventions in low- and middle-income countries.
ERK and Akt exhibit distinct signaling responses following stimulation by pro-angiogenic factors
Authors: Song Min , Finley Stacey D.
Published: July 2020

Background

Angiogenesis plays an important role in the survival of tissues, as blood vessels provide oxygen and nutrients required by the resident cells. Thus, targeting angiogenesis is a prominent strategy in many different settings, including both tissue engineering and cancer treatment. However, not all of the approaches that modulate angiogenesis lead to successful outcomes. Angiogenesis-based therapies primarily target pro-angiogenic factors such as vascular endothelial growth factor-A (VEGF) or fibroblast growth factor (FGF) in isolation, and there is a limited understanding of how these promoters combine together to stimulate angiogenesis. Targeting one pathway could be insufficient, as alternative pathways may compensate, diminishing the overall effect of the treatment strategy.

Methods

To gain mechanistic insight and identify novel therapeutic strategies, we have developed a detailed mathematical model to quantitatively characterize the crosstalk of FGF and VEGF intracellular signaling. The model focuses on FGF- and VEGF-induced mitogen-activated protein kinase (MAPK) signaling to promote cell proliferation and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway, which promotes cell survival and migration. We fit the model to published experimental datasets that measure phosphorylated extracellular regulated kinase (pERK) and Akt (pAkt) upon FGF or VEGF stimulation. We validate the model with separate sets of data.

Results

We apply the trained and validated mathematical model to characterize the dynamics of pERK and pAkt in response to the mono- and co-stimulation by FGF and VEGF. The model predicts that for certain ranges of ligand concentrations, the maximum pERK level is more responsive to changes in ligand concentration compared to the maximum pAkt level. Also, the combination of FGF and VEGF indicates a greater effect in increasing the maximum pERK compared to the summation of individual effects, which is not seen for maximum pAkt levels. In addition, our model identifies the influential species and kinetic parameters that specifically modulate the pERK and pAkt responses, which represent potential targets for angiogenesis-based therapies.

Conclusions

Overall, the model predicts the combination effects of FGF and VEGF stimulation on ERK and Akt quantitatively and provides a framework to mechanistically explain experimental results and guide experimental design. Thus, this model can be utilized to study the effects of pro- and anti-angiogenic therapies that particularly target ERK and/or Akt activation upon stimulation with FGF and VEGF.
Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models
Authors: Iba Michiyo , Kim Changyoun , Sallin Michelle , Kwon Somin , Verma Anjali , Overk Cassia , Rissman Robert A. , Sen Ranjan , Sen Jyoti Misra , Masliah Eliezer
Published: July 2020

Background

α-Synuclein (α-syn) is a pre-synaptic protein which progressively accumulates in neuronal and non-neuronal cells in neurodegenerative diseases such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy. Recent evidence suggests that aberrant immune activation may be involved in neurodegeneration in PD/DLB. While previous studies have often focused on the microglial responses, less is known about the role of the peripheral immune system in these disorders.

Methods

To understand the involvement of the peripheral immune system in PD/DLB, we evaluated T cell populations in the brains of α-syn transgenic (tg) mice (e.g., Thy1 promoter line 61) and DLB patients.

Results

Immunohistochemical analysis showed perivascular and parenchymal infiltration by CD3+/CD4+ helper T cells, but not cytotoxic T cells (CD3+/CD8+) or B cells (CD20+), in the neocortex, hippocampus, and striatum of α-syn tg mice. CD3+ cells were found in close proximity to the processes of activated astroglia, particularly in areas of the brain with significant astrogliosis, microgliosis, and expression of pro-inflammatory cytokines. In addition, a subset of CD3+ cells co-expressed interferon γ. Flow cytometric analysis of immune cells in the brains of α-syn tg mice revealed that CD1d-tet+ T cells were also increased in the brains of α-syn tg mice suggestive of natural killer T cells. In post-mortem DLB brains, we similarly detected increased numbers of infiltrating CD3+/CD4+ T cells in close proximity with blood vessels.

Conclusion

These results suggest that infiltrating adaptive immune cells play an important role in neuroinflammation and neurodegeneration in synucleinopathies and that modulating peripheral T cells may be a viable therapeutic strategy for PD/DLB.
Nuclear factor kappa B activation appears weaker in schizophrenia patients with high brain cytokines than in non-schizophrenic controls with high brain cytokines
Authors: Murphy Caitlin E. , Lawther Adam J. , Webster Maree J. , Asai Makoto , Kondo Yuji , Matsumoto Mitsuyuki , Walker Adam K. , Weickert Cynthia Shannon
Published: July 2020

Background

High inflammation status despite an absence of known infection characterizes a subpopulation of people with schizophrenia who suffer from more severe cognitive deficits, less cortical grey matter, and worse neuropathology. Transcripts encoding factors upstream of nuclear factor kappa B (NF-κB), a major transcriptional activator for the synthesis of pro-inflammatory cytokines, are increased in the frontal cortex in schizophrenia compared to controls. However, the extent to which these changes are disease-specific, restricted to those with schizophrenia and high-neuroinflammatory status, or caused by loss of a key NF-κB inhibitor (HIVEP2) found in schizophrenia brain, has not been tested.

Methods

Post-mortem prefrontal cortex samples were assessed in 141 human brains (69 controls and 72 schizophrenia) and 13 brains of wild-type mice and mice lacking HIVEP2 (6 wild-type, 7 knockout mice). Gene expression of pro-inflammatory cytokines and acute phase protein SERPINA3 was used to categorize high and low neuroinflammation biotype groups in human samples via cluster analysis. Expression of 18 canonical and non-canonical NF-κB pathway genes was assessed by qPCR in human and mouse tissue.

Results

In humans, we found non-canonical upstream activators of NF-κB were generally elevated in individuals with neuroinflammation regardless of diagnosis, supporting NF-κB activation in both controls and people with schizophrenia when cytokine mRNAs are high. However, high neuroinflammation schizophrenia patients had weaker (or absent) transcriptional increases of several canonical upstream activators of NF-κB as compared to the high neuroinflammation controls. HIVEP2 mRNA reduction was specific to patients with schizophrenia who also had high neuroinflammatory status, and we also found decreases in NF-κB transcripts typically induced by activated microglia in mice lacking HIVEP2.

Conclusions

Collectively, our results show that high cortical expression of pro-inflammatory cytokines and low cortical expression of HIVEP2 in a subset of people with schizophrenia is associated with a relatively weak NF-κB transcriptional signature compared to non-schizophrenic controls with high cytokine expression. We speculate that this comparatively milder NF-κB induction may reflect schizophrenia-specific suppression possibly related to HIVEP2 deficiency in the cortex.
Effect of AIDS-defining events at initiation of antiretroviral therapy on long-term mortality of HIV/AIDS patients in Southwestern China: a retrospective cohort study
Authors: Huang Yunxuan , Zhou Oulu , Zheng Zhigang , Xu Yuexiang , Shao Yi , Qin Chunwei , Qin Fengxiang , Lai Jingzhen , Liu Huifang , Chen Rongfeng , Ye Li , Liang Hao , Qin Xionglin , Jiang Junjun
Published: July 2020

Objective

To evaluate the impact of AIDS-defining events (ADE) on long-term mortality of HIV positive individuals on antiretroviral therapy (ART), a retrospective HIV/AIDS treatment cohort study performed in Southwestern China.

Methods

The retrospective cohort was conducted among 6757 HIV/AIDS patients on ART (2NRTIs + 1NNRTI, 2NRTIs + 1PI and Single or two drugs) recruited in Guigang city, Guangxi, China, from January 2004 to December 2018. Participants were divided into ADE and non-ADE groups, and were followed-up every six months to observe treatment outcomes. Comparison of mortality between groups was performed using the log-rank test and Kaplan–Meier analysis. Cox proportional hazard regression was used to explore the risk factors of mortality. 1:1 propensity score matching (PSM) was used to balance confounding factors and adjust the mortality risk.

Results

Of 6757 participants with 29,096.06 person-years of follow-up, 16.86% (1139/6757) belonged to ADE group while the others (83.14%) belonged to the non-ADE group. The most common cause of death by ADE was disseminated mycosis (31.65%), followed by recurrent severe bacterial pneumonia (28.48%), herpes zoster (17.72%), and extra-pulmonary tuberculosis (8.86%). The mortality of the ADE group was significantly higher than that of the non-ADE group [3.45/100 person-years (95% CI 2.92–3.97) vs. 2.34/100 person-years (95% CI 2.15–2.52), P<0.001]. The death risk of the ADE group was also higher than that of the non- ADE group [adjusted hazard ratio (aHR) = 1.291, 95% CI 1.061–1.571, P = 0.011], which was confirmed by PSM analysis (aHR = 1.581, 95% CI 1.192–2.099, P = 0.002). Cox analysis indicated that ADE, older age, male gender, previous non-use of cotrimoxazole, advanced WHO clinical stage, and low baseline CD4+ cell count were the risk factors for death.

Conclusions

Even on ART, the mortality risk of HIV positive individuals with ADE was higher than those without ADE. Active testing, earlier diagnosis, and timely therapy with ART may reduce the death risk of ADE.
Gut transcriptomic changes during hibernation in the greater horseshoe bat (Rhinolophus ferrumequinum)
Authors: Sun Haijian , Wang Jiaying , Xing Yutong , Pan Yi-Hsuan , Mao Xiuguang
Published: July 2020

Background

The gut is the major organ for nutrient absorption and immune response in the body of animals. Although effects of fasting on the gut functions have been extensively studied in model animals (e.g. mice), little is known about the response of the gut to fasting in a natural condition (e.g. hibernation). During hibernation, animals endure the long term of fasting and hypothermia.

Results

Here we generated the first gut transcriptome in a wild hibernating bat (Rhinolophus ferrumequinum). We identified 1614 differentially expressed genes (DEGs) during four physiological states (Torpor, Arousal, Winter Active and Summer Active). Gene co-expression network analysis assigns 926 DEGs into six modules associated with Torpor and Arousal. Our results reveal that in response to the stress of luminal nutrient deficiency during hibernation, the gut helps to reduce food intake by overexpressing genes (e.g. CCK and GPR17) that regulate the sensitivity to insulin and leptin. At the same time, the gut contributes energy supply by overexpressing genes that increase capacity for ketogenesis (HMGCS2) and selective autophagy (TEX264). Furthermore, we identified separate sets of multiple DEGs upregulated in Torpor and Arousal whose functions are involved in innate immunity.

Conclusion

This is the first gut transcriptome of a hibernating mammal. Our study identified candidate genes associated with regulation of food intake and enhance of innate immunity in the gut during hibernation. By comparing with previous studies, we found that two DEGs (CPE and HSPA8) were also significantly elevated during torpor in liver and brain of R. ferrumequinum and several DEGs (e.g. TXNIP and PDK1/4) were commonly upregulated during torpor in multiple tissues of different mammals. Our results support that shared expression changes may underlie the hibernation phenotype by most mammals.
Seroprevalence of anti-hepatitis E antibodies and antigens among HIV-infected patients in Fars Province, southern Iran
Authors: Shahriarirad Reza , Erfani Amirhossein , Rastegarian Mohammad , Zeighami Ali , Arefkhah Nasir , Ghorbani Fariba , Sarvari Jamal , Sarkari Bahador
Published: July 2020

Objective

HIV-infected patients have immunological and clinical features that might affect the pathogenesis, as well as the outcome of the HIV/HEV co-infection. The current study aimed to determine the seroprevalence of anti-HEV antibodies and HEV antigens among HIV-infected patients in Fars Province, Southwest Iran.

Methods

Blood samples (5 mL) were collected from 251 HIV-confirmed patients. Respective data, including patients’ demographic information, were obtained for each patient. The presence of HEV antigens and anti-HEV antibodies (IgG) were assessed by commercial ELISA kits, based on the manufacturers’ instructions.

Results

Out of 251 cases, 158 (62.9%) were male and 91 (36.3%) were female. Patients’ age varied from 14 to 83 (mean: 40 ± 9.7) years. Out of 251 HIV positive cases, 26 (10.4%) were positive for anti-HEV IgG antibodies and 6 (2.4%) were positive for HEV-antigens. Also, 2 (0.8%) of the patients were positive for both anti-HEV IgG antibodies and antigens. Statistical analysis revealed no significant association between sex and seropositivity to either HEV antigen or antibodies. Moreover, no significant association was seen between age and seropositivity to HEV antigen or antibody (P = 0.622 and 0.945, respectively).

Conclusion

Our results showed a relatively low prevalence of HEV-antibodies in HIV-infected patients, indicating that HIV positive patients may not be at greater risk of HEV infection than the general population. Moreover, HEV-antigen was detected in a few cases of HIV-infected individuals which indicate an acute or chronic HEV infection in these patients.
Fasciotomy through multiple small skin incisions for the treatment of early acute osteofascial compartment syndrome in children
Authors: Yuan Xiaowei , Wu Jun , Qu Xiangyang , Li Ming , Jiang Linjun , Liu Xing
Published: July 2020

Background

The purpose of the present study is to investigate the therapeutic effect of fasciotomy through multiple small skin incisions for the treatment of early osteofascial compartment syndrome in children.

Methods

From January 2009 to May 2017, 56 pediatric patients with early osteofascial compartment syndrome in their limbs were admitted into our department and treated with multiple small skin incisions for decompression at the early stage. The skin incisions, function, and sensation of the limbs were followed up.

Results

The osteofascial compartment syndrome was diagnosed at 7.4 ± 2.1 h after injury, and then fasciotomy was performed at 1.4 ± 0.4 h later. The average procedure time of fasciotomy was 12.7 ± 4.8 min. No postoperative incision infections or neurovascular injuries were observed in all the patients. The incisions completely healed in 7–10 days with an average healing time of 8 days without secondary suture. The patients were followed up for an average of 5.1 years. No Volkmann’s contractures in the injured limbs were found. The appearance, electromyography, and nerve conduction velocity of the affected limbs were not significantly different from that of the contralateral limbs. All the patients were free of symptoms and were fully recovered of sensation and function, being an “excellent” outcome at the latest follow-up.

Conclusion

Fasciotomy through multiple small skin incisions, which can be useful to decompress the compartment pressure with fewer complications, is a simple and effective strategy for the treatment of early osteofascial compartment syndrome in children.
Maintenance of certification for radiologists: an overview of European countries
Authors: Kwee Robert M. , Kwee Thomas C.
Published: July 2020

Background

It is currently unclear whether the continuing medical education (CME) requirements for radiologists to keep up their certification are equal across Europe, which would be desirable for uniform cross-border quality of radiology and because of the fundamental principle of free movement of workers in the European Union. This study aimed to determine the maintenance of certification requirements for radiologists in different European countries.

Methods

National radiological societies of European countries and/or their delegates as listed on the European Society of Radiology website were contacted to inquire about the maintenance of licensure requirements for radiologists in their country. Data were analysed using descriptive statistics.

Results

Forty-six European countries were contacted. Response rate was 80%. Twenty-two of 36 responding countries (59%) reported mandatory requirements to maintain a radiologist’s license to practise. The median license period was 5 years (range 1–7). The median required number of CME points per year was 40 (range 8–58, interquartile range 30). Eight countries reported additional requirements, including practising clinical radiology, attending quality meeting/clinical audit, and attending additional courses (such as radiation safety training and advanced medical training course). Fifteen of 37 responding countries (41%) did not report mandatory requirements.

Conclusions

There is considerable heterogeneity across European countries regarding the maintenance of certification requirements for radiologists. More homogeneity is desired for uniform quality assurance and professional mobility of radiologists across Europe. The data from our overview may be used to establish a benchmark for national societies who issue maintenance of licensure requirements for radiologists.
Antimicrobial activity of mesenchymal stem cells against Staphylococcus aureus
Authors: Yagi Haruyo , Chen Antonia F. , Hirsch David , Rothenberg Adam C. , Tan Jian , Alexander Peter G. , Tuan Rocky S.
Published: July 2020

Introduction

There have been limited advances in the treatment of bone and joint infections, which currently involves a combination of surgery and antibiotic administration. There is a timely need in orthopedics to develop more effective and less invasive forms of antimicrobial prophylaxis and treatment. The antibacterial effect of adult tissue-derived mesenchymal stem cells (MSCs) has recently been investigated against Escherichia coli and Staphylococcus aureus. The main mechanism of action is postulated to be via MSC production of the cationic antimicrobial peptide, LL-37.

Methods

This study examines the antimicrobial activity of adipose-derived human MSCs (ASCs) on S. aureus, specifically examining the role of LL-37 and regulation of its expression. Bacteria colony-forming unit (CFU) assay was used to assess antimicrobial activity.

Results

Our results showed that the ASC-conditioned medium significantly inhibited the growth of S. aureus under standard culture conditions with or without the continued presence of ASCs. Also, the treatment of ASCs with 1,25-dihydroxy vitamin D3 elevated LL-37 expression and enhanced their antimicrobial activity. In support, treatment with the vitamin D receptor inhibitor, GW0742, blocked the antimicrobial activity of ASCs.

Conclusion

Our findings clearly demonstrate the antimicrobial activity of adult ASCs against S. aureus and implicate a key regulatory role for vitamin D. Further testing in in vivo models is being pursued to assess the potential application of ASCs as a biocompatible, adjunct treatment for musculoskeletal infections.
Cardiac repair in a murine model of myocardial infarction with human induced pluripotent stem cell-derived cardiomyocytes
Authors: Jiang Xin , Yang Ziyi , Dong Ming
Published: July 2020

Background

Cellular replacement strategies using human induced pluripotent stem cells (iPSCs) and their cardiac derivatives are emerging as novel treatments for post-myocardial infarction (MI) heart failure (HF); however, the mechanism of recovery of heart function is not very clear. The purpose of this study was to investigate the efficiency of using highly purified human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) for myocardial repair in a mouse model of MI and to clarify the mechanism of recovery of heart function.

Methods

Animals modelling MI were randomly assigned to receive direct intramyocardial injection of culture medium (MI group) or 4 × 105 iPS-CMs (cell group) at the infarct border zone. Left ventricle (LV) performance was assessed with serial cardiac electrophysiology and was measured 1, 2 and 4 weeks post-MI. Invasive LV pressure measurement was measured at 4 weeks and was followed by sacrifice for histological examination.

Results

Compared to the MI group, the left ventricle ejection fraction (LVEF), left ventricular internal diameter in end-diastole (LVIDd) and end-systole (LVIDs) and maximal positive and negative pressure derivative (±dP/dt) were significantly improved in the iPS-CM group at 4 weeks post-MI. Histological examination revealed a very limited number of iPS-CMs 4 weeks after transplantation. Nonetheless, there was a significant enhancement of angiogenesis and a reduction in apoptosis of native cardiomyocyte after iPS-CM transplantation.

Conclusions

Our results demonstrate that transplantation of human iPS-CMs can improve heart function via paracrine action in a mouse model of myocardial infarction.
Human umbilical cord multipotent mesenchymal stromal cells alleviate acute ischemia-reperfusion injury of spermatogenic cells via reducing inflammatory response and oxidative stress
Authors: Zhong Liang , Yang Mengbo , Zou Xiangyu , Du Tao , Xu Huiming , Sun Jie
Published: July 2020

Background

This study was designed to determine the effect of human umbilical cord multipotent mesenchymal stromal cells (hUC-MSC) on acute ischemia/reperfusion (I/R) injury of spermatogenic cells.

Method

The testicular I/R rat model was established through 720° torsion for 1 h. hUC-MSC were intravenously injected 10 min before detorsion. Injury severity of spermatogenic cells was estimated by Johnsen’s score. The proliferating of recipient spermatogonia was measured by the immunostaining of antibodies against Ki67, and all germ cells were detected with DDX4 antibody. And recipient spermatogenesis was assessed by staining spermatozoa with lectin PNA. The levels of inflammatory factors were measured by real-time PCR. And the Selectin-E expression, neutrophil infiltration in the testes was detected by immunostaining. Germ cells apoptosis was tested by TUNEL assay and western blot. Furthermore, the oxidative stress was tested by reactive oxidative species (ROS) levels. In vitro, the condition medium (CM) of hUC-MSC was used to culture human umbilical vein endothelial cells (HUVECs), so as to assess the paracrine effect of hUC-MSC on HUVECs. The protein chip was used to measure the relative concentration of the secretory proteins in the CM of hUC-MSC.

Result

hUC-MSC greatly alleviated the testicular injury induced by testis I/R. The levels of proinflammatory factors were downregulated by hUC-MSC in vivo and in vitro. Neutrophil infiltration, ROS, and germ cell apoptosis in testicular tissues were greatly reduced in the group of hUC-MSC. Paracrine factors secreted by hUC-MSC including growth factors, cytokines, and anti-inflammatory cytokine were rich.

Conclusion

This study demonstrated that intravenously injected hUC-MSC could protect the spermatogenic cells against I/R injury by reducing the inflammatory response, apoptosis, and acute oxidative injury. Paracrine mechanism of hUC-MSC may contribute to the protection of spermatogenic cells against I/R injury. Therefore, the present study provides a method for clinical treatment of attenuate I/R injury of spermatogenic cells.
RETRACTED ARTICLE: Osteocyte-derived exosomes induced by mechanical strain promote human periodontal ligament stem cell proliferation and osteogenic differentiation via the miR-181b-5p/PTEN/AKT signaling pathway
Authors: Lv Pei-ying , Gao Peng-fei , Tian Guang-jie , Yang Yan-yan , Mo Fei-fei , Wang Zi-hui , Sun Lu , Kuang Ming-jie , Wang Yong-lan
Published: July 2020

Background

The oral cavity is a complex environment in which periodontal tissue is constantly stimulated by external microorganisms and mechanical forces. Proper mechanical force helps maintain periodontal tissue homeostasis, and improper inflammatory response can break the balance. Periodontal ligament (PDL) cells play crucial roles in responding to these challenges and maintaining the homeostasis of periodontal tissue. However, the mechanisms underlying PDL cell property changes induced by inflammatory and mechanical force microenvironments are still unclear. Recent studies have shown that exosomes function as a means of cell-cell and cell-matrix communication in biological processes.

Methods

Human periodontal ligament stem cells (HPDLSCs) were tested by the CCK8 assay, EdU, alizarin red, and ALP staining to evaluate the functions of exosomes induced by a mechanical strain. MicroRNA sequencing was used to find the discrepancy miRNA in exosomes. In addition, real-time PCR, FISH, luciferase reporter assay, and western blotting assay were used to investigate the mechanism of miR-181b-5p regulating proliferation and osteogenic differentiation through the PTEN/AKT pathway.

Results

In this study, the exosomes secreted by MLO-Y4 cells exposed to mechanical strain (Exosome-MS) contributed to HPDLSC proliferation and osteogenic differentiation. High-throughput miRNA sequencing showed that miR181b-5p was upregulated in Exosome-MS compared to the exosomes derived from MLO-Y4 cells lacking mechanical strain. The luciferase reporter assay demonstrated that miR-181b-5p may target phosphatase tension homolog deletion (PTEN). In addition, PTEN was negatively regulated by overexpressing miR-181b-5p. Real-time PCR and western blotting assay verified that miR-181b-5p enhanced the protein kinase B (PKB, also known as AKT) activity and improved downstream factor transcription. Furthermore, miR-181b-5p effectively ameliorated the inhibition of HPDLSC proliferation and promoted HPDLSC induced by inflammation.

Conclusions

This study concluded that exosomes induced by mechanical strain promote HPDLSC proliferation via the miR-181b-5p/PTEN/AKT signaling pathway and promote HPDLSC osteogenic differentiation by BMP2/Runx2, suggesting a potential mechanism for maintaining periodontal homeostasis.