bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of thromboembolism in patients with COVID-19: a systematic review and meta-analysis
Authors: Boonyawat Kochawan , Chantrathammachart Pichika , Numthavaj Pawin , Nanthatanti Nithita , Phusanti Sithakom , Phuphuakrat Angsana , Niparuck Pimjai , Angchaisuksiri Pantep
Published: November 2020

Background

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, the incidence of thromboembolism has been increasingly reported. The aim of this systematic review was to explore the incidence of venous and arterial thromboembolism among COVID-19 patients requiring hospitalization.

Methods

Medline, Embase, Scopus, and grey literature were searched until June 2020. Observational studies reported on the incidence of venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) or arterial thromboembolism (ATE) were included. The pool incidences and their 95% confidence intervals (CI) were calculated using the random-effects model.

Results

A total of 36 studies were included. In the intensive care unit (ICU) setting, the pooled incidence of VTE was 28% (95% CI, 22–34%). Subgroups based on compression ultrasound (CUS) screening revealed a higher incidence of DVT in the CUS screening group than in the no CUS screening group (32% [95% CI, 18–45%] vs. 6% [95% CI, 4–9%]). The pooled incidence of ATE in ICU was 3% (95% CI, 2–5%). In the non-ICU setting, the pooled incidence of VTE was 10% (95% CI, 6–14%,).

Conclusions

The incidence of VTE in COVID-19 patients was higher in the ICU setting than in the non-ICU setting, and also significantly higher in studies that incorporated the CUS screening protocol. The incidence of ATE in the ICU setting was low. VTE prophylactic measures should be given to all hospitalized patients diagnosed with COVID-19.
Synergistic effects of EMPs and PMPs on pulmonary vascular leakage and lung injury after ischemia/reperfusion
Authors: Zhang Jie , Zhu Yu , Wu Yue , Yan Qing-Guang , Peng Xiao-Yong , Xiang Xin-Ming , Xue Ming-Ying , Li Qing-Hui , Liu Liang-Ming , Li Tao
Published: November 2020

Background

Vascular leakage is an important pathophysiological process of critical conditions such as shock and ischemia–reperfusion (I/R)-induced lung injury. Microparticles (MPs), including endothelial cell-derived microparticles (EMPs), platelet-derived microparticles (PMPs) and leukocyte-derived microparticles (LMPs), have been shown to participate in many diseases. Whether and which of these MPs take part in pulmonary vascular leakage and lung injury after I/R and whether these MPs have synergistic effect and the underlying mechanism are not known.

Methods

Using hemorrhage/transfusion (Hemo/Trans) and aorta abdominalis occlusion-induced I/R rat models, the role of EMPs, PMPs and LMPs and the mechanisms in pulmonary vascular leakage and lung injury were observed.

Results

The concentrations of EMPs, PMPs and LMPs were significantly increased after I/R. Intravenous administration of EMPs and PMPs but not LMPs induced pulmonary vascular leakage and lung injury. Furthermore, EMPs induced pulmonary sequestration of platelets and promoted more PMPs production, and played a synergistic effect on pulmonary vascular leakage. MiR-1, miR-155 and miR-542 in EMPs, and miR-126 and miR-29 in PMPs, were significantly increased after hypoxia/reoxygenation (H/R). Of which, inhibition of miR-155 in EMPs and miR-126 in PMPs alleviated the detrimental effects of EMPs and PMPs on vascular barrier function and lung injury. Overexpression of miR-155 in EMPs down-regulated the expression of tight junction related proteins such as ZO-1 and claudin-5, while overexpression of miR-126 up-regulated the expression of caveolin-1 (Cav-1), the trans-cellular transportation related protein such as caveolin-1 (Cav-1). Inhibiting EMPs and PMPs production with blebbistatin (BLE) and amitriptyline (AMI) alleviated I/R induced pulmonary vascular leakage and lung injury.

Conclusions

EMPs and PMPs contribute to the pulmonary vascular leakage and lung injury after I/R. EMPs mediate pulmonary sequestration of platelets, producing more PMPs to play synergistic effect. Mechanically, EMPs carrying miR-155 that down-regulates ZO-1 and claudin-5 and PMPs carrying miR-126 that up-regulates Cav-1, synergistically mediate pulmonary vascular leakage and lung injury after I/R.

Graphic abstract
The COX-2-derived PGE2 autocrine contributes to bradykinin-induced matrix metalloproteinase-9 expression and astrocytic migration via STAT3 signaling
Authors: Lee Tsong-Hai , Liu Pei-Shan , Tsai Ming-Ming , Chen Jiun-Liang , Wang Su-Jane , Hsieh Hsi-Lung
Published: November 2020

Background

The matrix metalloproteinase-9 (MMP-9) is up-regulated by several proinflammatory mediators in the central nervous system (CNS) diseases. Increasing reports show that MMP-9 expression is an inflammatory biomarker of several CNS disorders, including the CNS inflammation and neurodegeneration. Bradykinin (BK) is a common proinflammatory mediator and elevated in several brain injury and inflammatory disorders. The raised BK may be detrimental effects on the CNS that may aggravate brain inflammation through MMP-9 up-regulation or cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production in brain astrocytes. However, the relationship between BK-induced MMP-9 expression and COX-2-derived PGE2 release in brain astrocytes remains unclear.

Methods

Herein we used rat brain astrocytes (RBA) to investigate the role of the COX-2/PGE2 system in BK-induced MMP-9 expression. We used zymographic, RT-PCR, EIA, and Western blotting analyses to confirm that BK induces MMP-9 expression via a COX-2/PGE2-dependent pathway.

Results

Our results show activation of native COX-2 by BK led to PGE2 production and release. Subsequently, PGE2 induced MMP-9 expression via PGE2 receptor (EP)-mediated c-Src, Jak2, ERK1/2, and then activated signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, up-regulation of MMP-9 by BK via the pathway may promote astrocytic migration.

Conclusion

These results demonstrated that a novel autocrine pathway for BK-induced MMP-9 protein expression is mediated through activation of STAT3 by native COX-2/PGE2-mediated c-Src/Jak2/ERK cascades in brain astrocytes.
The accelerator, the brake, and the terrain: associations of reward-related eating, self-regulation, and the home food environment with diet quality during pregnancy and postpartum in the pregnancy eating attributes study (PEAS) cohort
Authors: Nansel Tonja R. , Lipsky Leah M. , Faith Myles , Liu Aiyi , Siega-Riz Anna Maria
Published: November 2020

Background

Neurobehavioral factors, including reward-related eating and self-regulation, in conjunction with the food environment, may influence dietary behaviors. However, these constructs have not been examined in pregnancy and postpartum, a time of changing appetite and eating behaviors, and when dietary intake has implications for maternal and child health. This study examined associations of reward-related eating, self-regulation, and the home food environment with pregnancy and postpartum diet quality.

Methods

Participants in the Pregnancy Eating Attributes Study observational cohort were enrolled at ≤12 weeks gestation and followed through one-year postpartum. Pregnancy and postpartum Healthy Eating Index-2015 (HEI-total), and adequacy and moderation scores, respectively, were calculated by pooling 24-h diet recalls administered each trimester and during 2, 6, and 12 months postpartum. Participants completed four measures of reward-related eating – Modified Yale Food Addiction Scale (mYFAS), Power of Food Scale (PFS), Multiple Choice Procedure (MCP), and Reinforcing Value of Food Questionnaire (RVFQ); two measures of self-regulation – Barratt Impulsiveness Scale (BIS) and Delay of Gratification Inventory (DGI); and a Home Food Inventory (HFI), yielding obesogenic (OBES) and fruit/vegetables (FV) scores. Linear regression analyses estimated associations of reward-related eating, self-regulation, and home food environment with diet quality during pregnancy and postpartum, adjusting for sociodemographic characteristics.

Results

Pregnancy HEI-total was inversely associated with PFS (β = − 0.14 ± 0.05, p = 0.009), mYFAS(β = − 0.14 ± 0.06, p = 0.02), 2 of the 5 RVFQ indices, MCP (β = − 0.14 ± 0.05, p = 0.01), and DGI food subscale (β = 0.23 ± 0.05, p < 0.001), but associations of postpartum HEI-total with reward-related eating measures and self-regulation were small and not statistically significant. Pregnancy and postpartum HEI-total were associated inversely with HFI-OBES (β = − 0.17 ± 0.06, p = 0.004 and β = − 0.19 ± 0.07, p = 0.006, respectively), and positively with HFI-FV (β = 0.21 ± 0.05, p < 0.001 and β = 0.17 ± 0.06, p = 0.009, respectively).

Conclusions

Associations of poorer diet quality with greater reward-related eating during pregnancy but not postpartum suggests the need to better understand differences in the determinants of eating behaviors and approaches to circumvent or moderate reward-related eating to facilitate more optimal diet quality across this critical period.

Trial registration

Clinicaltrials.gov. URL – Registration ID – NCT02217462. Date of registration – August 13, 2014.
Tespa1 plays a role in the modulation of airway hyperreactivity through the IL-4/STAT6 pathway
Authors: Yang Ruhui , Wang Guangli , Li Lingyun , He Hanjiang , Zheng Mingzhu , Lu Linrong , Wu Songquan
Published: November 2020

Background

Thymocyte-expressed, positive selection-associated 1 (Tespa1) is a critical signaling molecule in thymocyte development. This study aimed to investigate the regulatory effect of Tespa1 on mast cells in the pathogenesis of asthma and its relationship with the interleukin (IL)-4/signal transducers and activators of transcription 6 (STAT6) signaling pathway.

Methods

Tespa1 mRNA expression analysis and IgE levels were carried out using the induced sputum of 33 adults with stable asthma and 36 healthy controls. Tespa1-knockout mice (Tespa1−/−, KO) and C57BL/6 background (wild-type, WT) mice were sensitized and treated with ovalbumin (OVA) to establish an asthma model. Pathological changes, number and activity of mast cells, and changes in activation of the IL-4/STAT6 pathway in lung tissue were detected. The changes of tryptase expression and STAT6 activation after mast cell gene knockout were analyzed in vitro. The changes of enzyme expression and STAT6 activation after mast cell gene knockout were analyzed in vitro. The association between the Tespa1 and p-STAT6 was analyzed by co-immunoprecipitation method.

Results

Compared with the healthy controls, Tespa1 expression was decreased, and IgE levels were elevated in the sputum of asthmatic patients. Animal experiments showed that Tespa1−/− mice exhibited more severe inflammation, higher quantity of goblet cells and mast cells in the bronchium, and greater expression of mast cell tryptase, which is induced by ovalbumin, than WT mice. And IL-4, IL-13, phospho-Janus kinase 1, and p-STAT6 expressions presented a higher increase in the Tespa1−/− mouse model than in the WT mouse model. Further in vitro studies confirmed that IL-4 could more significantly promote tryptase and p-STAT6 activities in Tespa1−/− mast cells than their WT counterparts. Correlation analysis results showed a negative correlation between Tespa1 and p-STAT6. Co-immunoprecipitation results demonstrated an association between Tespa1 and p-STAT6.

Conclusions

Altogether, our results indicate that Tespa1 can negatively regulate mast cell activity, and this event is related to the mast cell IL-4/STAT6 signaling pathway and could be therapeutically exploited to treat asthma attacks.
Inconsistent reversal of HIV-1 latency ex vivo by antigens of HIV-1, CMV, and other infectious agents
Authors: Vollbrecht Thomas , Angerstein Aaron O. , Menke Bryson , Kumar Nikesh M. , de Oliveira Michelli Faria , Richman Douglas D. , Guatelli John C.
Published: November 2020

Background

A reservoir of replication-competent but latent virus is the main obstacle to a cure for HIV-1 infection. Much of this reservoir resides in memory CD4 T cells. We hypothesized that these cells can be reactivated with antigens from HIV-1 and other common pathogens to reverse latency.

Results

We obtained mononuclear cells from the peripheral blood of antiretroviral-treated patients with suppressed viremia. We tested pools of peptides and proteins derived from HIV-1 and from other pathogens including CMV for their ability to reverse latency ex vivo by activation of memory responses. We assessed activation of the CD4 T cells by measuring the up-regulation of cell-surface CD69. We assessed HIV-1 expression using two assays: a real-time PCR assay for virion-associated viral RNA and a droplet digital PCR assay for cell-associated, multiply spliced viral mRNA. Reversal of latency occurred in a minority of cells from some participants, but no single antigen induced HIV-1 expression ex vivo consistently. When reversal of latency was induced by a specific peptide pool or protein, the extent was proportionally greater than that of T cell activation.

Conclusions

In this group of patients in whom antiretroviral therapy was started during chronic infection, the latent reservoir does not appear to consistently reside in CD4 T cells of a predominant antigen-specificity. Peptide-antigens reversed HIV-1 latency ex vivo with modest and variable activity. When latency was reversed by specific peptides or proteins, it was proportionally greater than the extent of T cell activation, suggesting partial enrichment of the latent reservoir in cells of specific antigen-reactivity.
A qualitative study of factors influencing male participation in fertility research
Authors: Harlow Alyssa F. , Zheng Amy , Nordberg John , Hatch Elizabeth E. , Ransbotham Sam , Wise Lauren A.
Published: November 2020

Background

Although fertility is a couple-based outcome, fertility studies typically include far fewer males than females. We know little about which factors facilitate or inhibit male participation in fertility research. In this study we aimed to explore factors that influence male participation in fertility research among North American couples trying to conceive.

Methods

We conducted a qualitative research study of male participation in Pregnancy Study Online (PRESTO), a prospective preconception cohort of couples actively trying to conceive in Canada and the United States. Between January–August 2019, we carried out 14 online one-on-one in-depth interviews and one online focus group of males and females with varying levels of participation. The in-depth interviews included females who enrolled in PRESTO but declined to invite their male partners to participate (n = 4), males who enrolled in PRESTO (n = 6), and males who declined to participate in PRESTO (n = 4). The focus group included 10 males who enrolled in PRESTO. We analyzed the transcriptions using inductive content analysis.

Results

Male and female participants perceived that fertility is a women’s health issue and is a difficult topic for men to discuss. Men expressed fears of infertility tied to masculinity. However, men were motivated to participate in fertility research to support their partners, provide data that could help others, and to learn more about their own reproductive health.

Conclusions

Male participation in fertility studies will improve our understanding of male factors contributing to fertility and reproductive health issues. Results indicate a need for more education and health communication on male fertility to normalize male participation in fertility and reproductive health research.

Plain English Summary

Men are much less likely than women to participate in research on fertility and pregnancy. However, it is important for men to participate in fertility research so that we gain a better understanding of male factors that impact fertility and pregnancy outcomes. In this qualitative study, we interviewed men and women from Canada and the United States who were trying to become pregnant to understand why men choose to participate in fertility research, why men choose not to participate in fertility research, and why women choose not to invite their male partners to participate in fertility research. We found that both men and women believe fertility is a woman’s health issue. Men find it difficult to talk about pregnancy and fertility and have fears of infertility tied to masculinity. However, men are motivated to participate in fertility research to support their partners, to help others, and to learn more about their own reproductive health.
Comparing methods of performing geographically targeted rural health surveillance
Authors: Lee David C. , McGraw Nancy A. , Doran Kelly M. , Mengotto Amanda K. , Wiener Sara L. , Vinson Andrew J. , Thorpe Lorna E.
Published: November 2020

Background

Worsening socioeconomic conditions in rural America have been fueling increases in chronic disease and poor health. The goal of this study was to identify cost-effective methods of deploying geographically targeted health surveys in rural areas, which often have limited resources. These health surveys were administered in New York’s rural Sullivan County, which has some of the poorest health outcomes in the entire state.

Methods

Comparisons were made for response rates, estimated costs, respondent demographics, and prevalence estimates of a brief health survey delivered by mail and phone using address-based sampling, and in-person using convenience sampling at a sub-county level in New York’s rural Sullivan County during 2017.

Results

Overall response rates were 27.0% by mail, 8.2% by phone, and 71.4% for convenience in-person surveys. Costs to perform phone surveys were substantially higher than mailed or convenience in-person surveys. All modalities had lower proportions of Hispanic respondents compared to Census estimates. Unadjusted and age-adjusted prevalence estimates were similar between mailed and in-person surveys, but not for phone surveys.

Conclusions

These findings are consistent with declining response rates of phone surveys, which obtained an inadequate sample of rural residents. Though in-person surveys had higher response rates, convenience sampling failed to obtain a geographically distributed sample of rural residents. Of modalities tested, mailed surveys provided the best opportunity to perform geographically targeted rural health surveillance.
Evaluation on the use of Nanopore sequencing for direct characterization of coronaviruses from respiratory specimens, and a study on emerging missense mutations in partial RdRP gene of SARS-CoV-2
Authors: Chan Wai Sing , Au Chun Hang , Lam Ho Yin , Wang Candy Ling Na , Ho Dona Ngar-Yin , Lam Yuk Man , Chu Daniel Ka Wing , Poon Leo Lit Man , Chan Tsun Leung , Zee Jonpaul Sze-Tsing , Ma Edmond Shiu Kwan , Tang Bone Siu Fai
Published: November 2020

Coronavirus disease 2019 (COVID-19) pandemic has been a catastrophic burden to global healthcare systems. The fast spread of the etiologic agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the need to identify unknown coronaviruses rapidly for prompt clinical and public health decision making. Moreover, owing to the high mutation rate of RNA viruses, periodic surveillance on emerging variants of key virus components is essential for evaluating the efficacy of antiviral drugs, diagnostic assays and vaccines. These 2 knowledge gaps formed the basis of this study. In the first place, we evaluated the feasibility of characterizing coronaviruses directly from respiratory specimens. We amplified partial RdRP gene, a stable genetic marker of coronaviruses, from a collection of 57 clinical specimens positive for SARS-CoV-2 or other human coronaviruses, and sequenced the amplicons with Nanopore Flongle and MinION, the fastest and the most scalable massively-parallel sequencing platforms to-date. Partial RdRP sequences were successfully amplified and sequenced from 82.46% (47/57) of specimens, ranging from 75 to 100% by virus type, with consensus accuracy of 100% compared with Sanger sequences available (n = 40). In the second part, we further compared 19 SARS-CoV-2 RdRP sequences collected from the first to third waves of COVID-19 outbreak in Hong Kong with 22,173 genomes from GISAID EpiCoV™ database. No single nucleotide variants (SNVs) were found in our sequences, and 125 SNVs were observed from global data, with 56.8% being low-frequency (n = 1–47) missense mutations affecting the rear part of RNA polymerase. Among the 9 SNVs found on 4 conserved domains, the frequency of 15438G > T was highest (n = 34) and was predominantly found in Europe. Our data provided a glimpse into the sequence diversity of a primary antiviral drug and diagnostic target. Further studies are warranted to investigate the significance of these mutations.
Genetic characterization of a Marek’s disease virus strain isolated in Japan
Authors: Murata Shiro , Machida Yuka , Isezaki Masayoshi , Maekawa Naoya , Okagawa Tomohiro , Konnai Satoru , Ohashi Kazuhiko
Published: November 2020

Background

Marek’s disease virus (MDV) causes malignant lymphomas in chickens (Marek’s disease, MD). MD is currently controlled by vaccination; however, MDV strains have a tendency to develop increased virulence. Distinct diversity and point mutations are present in the Meq proteins, the oncoproteins of MDV, suggesting that changes in protein function induced by amino acid substitutions might affect MDV virulence. We previously reported that recent MDV isolates in Japan display distinct mutations in Meq proteins from those observed in traditional MDV isolates in Japan, but similar to those in MDV strains isolated from other countries.

Methods

To further investigate the genetic characteristics in Japanese field strains, we sequenced the whole genome of an MDV strain that was successfully isolated from a chicken with MD in Japan. A phylogenetic analysis of the meq gene was also performed.

Results

Phylogenetic analysis revealed that the Meq proteins in most of the Japanese isolates were similar to those of Chinese and European strains, and the genomic sequence of the Japanese strain was classified into the Eurasian cluster. Comparison of coding region sequences among the Japanese strain and MDV strains from other countries revealed that the genetic characteristics of the Japanese strain were similar to those of Chinese and European strains.

Conclusions

The MDV strains distributed in Asian and European countries including Japan seem to be genetically closer to each other than to MDV strains from North America. These findings indicate that the genetic diversities of MDV strains that emerged may have been dependent on the different vaccination-based control approaches.
Experiences of workplace breastfeeding in a provincial government setting: a qualitative exploratory study among managers and mothers in South Africa
Authors: Mabaso Bongekile P. , Jaga Ameeta , Doherty Tanya
Published: November 2020

Background

Return to employment is a major barrier to breastfeeding continuation, globally and in the Southern African context. The Lancet Breastfeeding Series revealed an explicit need for research exploring breastfeeding as a workplace issue in low- and middle-income countries. A dearth of research on workplace breastfeeding in South Africa calls for attention to this topic. This study sought to explore breastfeeding at work experiences from the perspective of employed mothers and senior managers in a provincial government setting in South Africa.

Methods

The study adopted an exploratory qualitative design with multi-perspective semi-structured interviews. Snowball sampling was employed to recruit twelve participants, senior managers (n = 4) and employed mothers (n = 8), from two provincial government departments in Cape Town, South Africa. Interviews were conducted between April and August 2018 to capture participants’ experiences with breastfeeding in the workplace. Thematic analysis was used to analyse data.

Results

Four key themes that described experiences of workplace breastfeeding emerged which further traversed three critical maternity periods: pregnancy, maternity leave, and return to work. The prevalent themes were: 1) Knowledge about the legislation and breastfeeding support benefits. Most participants only knew about the legislated four months maternity leave and time off for prenatal visits but lacked knowledge about comprehensive maternity benefits; 2) Perceptions and experiences of breastfeeding in the workplace. Breastfeeding was perceived to be a mother’s responsibility and a private issue. As a result, most participants stopped breastfeeding prior to or immediately upon return to work after maternity leave; 3) Barriers to breastfeeding continuation, such as the absence of a conversation about infant feeding plans between managers and mothers; and 4) Recommendations to improve breastfeeding support at work from an individual, organisational and national level.

Conclusions

Our study contributions emphasise that breastfeeding support from managers should begin prior to the mother taking maternity leave, and that in addition to providing supportive facilities (such as private space and breastmilk storage), immediate supervisor support may be critical in fostering breastfeeding-friendly workplaces for mothers. Management implications for advancing workplace breastfeeding support in the public sector are presented.
“I think everybody should take it if they’re doing drugs, doing heroin, or having sex for money”: a qualitative study exploring perceptions of pre-exposure prophylaxis among female participants in an opioid intervention court program
Authors: Przybyla Sarahmona M. , Cerulli Catherine , Bleasdale Jacob , Wilson Kennethea , Hordes Melissa , El-Bassel Nabila , Morse Diane S.
Published: November 2020

Background

Women’s rise in opioid use disorder has increased their presence in the criminal justice system and related risk behaviors for HIV infection. Although pre-exposure prophylaxis (PrEP) is an effective biomedical HIV prevention treatment, uptake among this high-risk population has been particularly low. Considerably little is known about the interplay between justice-involved women with opioid use disorder and HIV prevention. The aim of this study was to explore PrEP knowledge, attitudes, and perceptions for personal and partner use among women participants in the nation’s first ever opioid intervention court program.

Methods

The authors conducted semi-structured, in-depth interviews with 31 women recruited from an Opioid Intervention Court, a recent fast-track treatment response to combat overdose deaths. We utilized a consensual qualitative research approach to explore attitudes, perceptions, and preferences about PrEP from women at risk for HIV transmission via sexual and drug-related behavior and used thematic analysis methods to code and interpret the data.

Results

PrEP interest and motivation were impacted by various factors influencing the decision to consider PrEP initiation or comfort with partner use. Three primary themes emerged: HIV risk perceptions, barriers and facilitators to personal PrEP utilization, and perspectives on PrEP use by sexual partners.

Conclusions

Findings suggest courts may provide a venue to offer women PrEP education and HIV risk assessments. Study findings inform public health, substance use, and criminal justice research and practice with justice-involved participants experiencing opioid use disorder on the development of gender-specific PrEP interventions with the ultimate goal of reducing HIV incidence.
Arthroscopic fixation of humeral greater tuberosity fracture using a W-shaped suture
Authors: Lin Xiaocong , Huang Xiuxi , Fang Kaibin , Dai Zhangsheng
Published: November 2020

Background

Patients with greater tuberosity fractures of the humerus often require surgery. Therefore, there is a need to find a minimally invasive and effective surgical procedure with great patient outcomes.

Aim

To evaluate the clinical outcomes of the W-shaped suture technique under shoulder arthroscopy in the treatment of greater tuberosity fractures of the humerus.

Methods

In this retrospective study, a total of 17 patients were included. The fractures were closed, and there was no neurovascular injury. These patients underwent arthroscopically assisted reduction and internal fixation of the greater tuberosity fractures. Fixation was performed using sighting nails combined with a W-shaped suture. The imaging data of the patients were collected, and the ASES score, Constant-Murley score, and VAS score were used to evaluate the patient’s outcome. At the last follow-up (at least 1 year), the range of motion in the affected shoulder was compared with that of the contralateral side.

Results

The operation was successful in all the patients. The average follow-up time was 13 months. There were no reported complications such as fracture displacement, nonunion, and internal fixation failure during the follow-up period. Post-operative X-ray examinations revealed good function recovery, with a healing time of between 10 and 12 weeks, and an average healing time of 11.5 weeks. Following the operation, patients reported reduced shoulder joint pain that no longer influenced their activity or caused discomfort in their daily life. The patient’s VAS score ranged from 0 to 3, with an average of 0.52 ± 0.73, while at the last follow-up, the Constant-Murley score ranged from 83 to 97, with an average of 92.33 ± 7.55. The ASES score ranged from 81 to 98, with an average of 93.15 ± 6.93. At the last follow-up, there was no significant difference in the overall range of motion with the unaffected limb.

Conclusion

This study demonstrates that the W-shaped suture can be used to effectively fix the fractures of the greater tuberosity of the humerus, by increasing the fixed area to promote healing.
Langerhans cell histiocytosis of the rib presenting with pathological fracture: a case report
Authors: Zuo Tao , Jiang Ping , Yu Junjie , Zhao Ke , Liu Yong , Chen Baojun
Published: November 2020

Introduction

Langerhans cell histiocytosis (LCH) is a rare neoplastic hyperplasia with an unknown etiology. It is clinically rare for patients with solitary rib lesion and pathological fracture; moreover, its diagnosis and treatment are quite difficult. The purpose of this study is to present a case for the pathogenesis, clinical features, imaging, and treatment of this disease.

Case presentation

A 52-year-old female patient complained of left chest pain for one week. CT showed a fracture in the left 5th rib. The rib tumor was then resected and the surrounding muscles and soft tissues were accordingly resected. The patient was diagnosed with pathological rib fracture, and the patient was pathologically diagnosed with LCH. After surgery, no local recurrence or distant metastasis was reported during the two-year follow-up.

Conclusions

LCH should be treated by observation, chemotherapy, radiotherapy, or surgery, or using a combination of several methods. Moreover, primary tumor should be considered when rib fracture without trauma and tumor metastasis.
Flock-level risk factors for outbreaks of infectious arthritis in lambs, Norway 2018
Authors: Smistad Marit , Wolff Cecilia , Tollersrud Tore , Tømmerberg Vibeke , Phythian Clare , Kampen Annette Hegermann , Jørgensen Hannah Joan
Published: November 2020

Background

Outbreaks of infectious arthritis in young lambs associated with Streptococcus dysgalactiae subspecies dysgalactiae (SDSD) lead to reduced animal welfare, increased use of antibiotics and economic losses for sheep farmers. Understanding risk factors is essential when developing strategies to prevent such outbreaks. This questionnaire-based cross-sectional study classified sheep flocks of respondents as cases or controls. Flock-level risk factors for outbreaks of infectious arthritis were assessed using a multivariable logistic regression model.

Results

Eighty-four of 1498 respondents (5.6%) experienced an outbreak of infectious arthritis in their flock in 2018, the year of study. Factors associated with a higher risk of outbreak were larger flock size (OR 1.3, 95% CI 1.1–1.4, per 100 lambs), plastic mesh flooring in the lambing pen (OR 3.0, 95% CI 1.7–5.3) and a lambing percentage greater than 200 (OR 2.0, 95% CI 1.1–3.5). Flocks where farmers observed infections around the ear tags of lambs also had an increased risk of outbreak (OR 2.6, 95% CI 1.6–4.3).

Conclusions

The risk factors identified in this study are characteristic of modern and intensively managed sheep farms in Norway. A distinguishing feature of Norwegian sheep farming is winter housing and indoor lambing. One might expect that this in itself is a risk factor because of high stocking densities during lambing. However, outbreaks of infectious arthritis in young lambs are reported by the industry to be a more recent phenomenon. The current study indicates that intensification of indoor management systems with larger flocks and higher production per ewe may predispose to outbreaks. The results provide a basis for further studies on transmission dynamics of SDSD in sheep flocks with indoor lambing.
Up-regulation of VANGL1 by IGF2BPs and miR-29b-3p attenuates the detrimental effect of irradiation on lung adenocarcinoma
Authors: Hao Chun-cheng , Xu Cui-yang , Zhao Xin-yu , Luo Jia-ning , Wang Gang , Zhao Li-hong , Ge Xiaofeng , Ge Xiao-feng
Published: November 2020

Accumulating evidence suggests that radiation treatment causes an adaptive response of lung adenocarcinoma (LUAD), which in turn attenuates the lethal effect of the irradiation. Previous microarray assays manifested the change of gene expression profile after irradiation. Bioinformatics analysis of the significantly changed genes revealed that VANGL1 may notably influence the effect of radiation on LUAD. To determine the role of VANGL1, this study knocked down or overexpressed VANGL1 in LUAD. M6A level of VANGL1 mRNA was determined by M6A-IP-qPCR assay. Irradiation caused the up-regulation of VANGL1 with the increase of VANGL1 m6A level. Depletion of m6A readers, IGF2BP2/3, undermined VANGL1 mRNA stability and expression upon irradiation. miR-29b-3p expression was decreased by irradiation, however VANGL1 is a target of miR-29b-3p which was identified by Luciferase report assay. The reduction of miR-29b-3p inhibited the degradation of VANGL1 mRNA. Knockdown of VANGL1 enhanced the detrimental effect of irradiation on LUAD, as indicated by more severe DNA damage and increased percentage of apoptotic cells. Immunocoprecipitation revealed the interaction between VANGL1 with BRAF. VANGL1 increased BRAF probably through suppressing the protein degradation, which led to the increase of BRAF downstream effectors, TP53BP1 and RAD51. These effectors are involved in DNA repair after the damage. In summary, irradiation caused the up-regulation of VANGL1, which, in turn, mitigated the detrimental effect of irradiation on LUAD by protecting DNA from damage probably through activating BRAF/TP53BP1/RAD51 cascades. Increased m6A level of VANGL1 and reduced miR-29b-3p took the responsibility of VANGL1 overexpression upon irradiation.
A novel circular RNA circ-LRIG3 facilitates the malignant progression of hepatocellular carcinoma by modulating the EZH2/STAT3 signaling
Authors: Sun Suofeng , Gao Jing , Zhou Shen , Li Yuan , Wang Yu , Jin Li , Li Jian , Liu Bowei , Zhang Bingyong , Han Shuangyin , Ding Hui , Li Xiuling
Published: November 2020

Background

Circular RNA (circRNA) is emerging as an important player in human diseases, especially cancer. In our previous study, we identified a series of deregulated circRNAs in hepatocellular carcinoma (HCC) by performing circRNA microarray expression profile. Here, we aimed to explore the role of circ-LRIG3 (hsa_circ_0027345) in HCC.

Methods

qRT-PCR and western blot were used to asses gene and protein expression, respectively. CCK-8, EdU and Transwell assays were used to detect cell proliferation, migration and invasion. GSEA software was applied to analyze the pathway related to circ-LRIG3. Co-IP, RIP and ChIP assays were used to identify the positive feedback axis of circ-LRIG3/EZH2/STAT3. Animal study was carried to test the role of circ-LRIG3 in vivo.

Results

Circ-LRIG3 was notably upregulated in HCC and promoted HCC cell proliferation, migration, invasion and reduced apoptosis. Circ-LRIG3 formed a ternary complex with EZH2 and STAT3, facilitating EZH2-induced STAT3 methylation and subsequent phosphorylation, resulting in the activation of STAT3 signaling. In turn, activated STAT3 could directly bind to circ-LRIG3 promoter to increase circ-LRIG3 transcription activity, thus forming a positive feedback loop. The animal models showed that exogenous expression of circ-LRIG3 enhanced tumorigenicity and metastasis in vivo, whereas these effects were blocked after treatment with C188–9, a specific STAT3 small-molecule inhibitor. Clinically, high circ-LRIG3 was closely linked with aggressive clinicopathological features and was identified as an independent risk prognostic factor of overall survival. Importantly, plasma circ-LRIG3 was found to be a highly sensitive and specific non-invasive diagnostic indicator for HCC.

Conclusions

Our study reveals the carcinogenic role of circ-LRIG3 in HCC, which may provide a new therapeutic target for HCC patients.
Dosing of thromboprophylaxis and mortality in critically ill COVID-19 patients
Authors: Jonmarker Sandra , Hollenberg Jacob , Dahlberg Martin , Stackelberg Otto , Litorell Jacob , Everhov Åsa H. , Järnbert-Pettersson Hans , Söderberg Mårten , Grip Jonathan , Schandl Anna , Günther Mattias , Cronhjort Maria
Published: November 2020

Background

A substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are associated with lower mortality rates. The purpose of the study was to evaluate the association between initial dosing strategy of thromboprophylaxis in critically ill COVID-19 patients and the risk of death, thromboembolism, and bleeding.

Method

In this retrospective study, all critically ill COVID-19 patients admitted to two intensive care units in March and April 2020 were eligible. Patients were categorized into three groups according to initial daily dose of thromboprophylaxis: low (2500–4500 IU tinzaparin or 2500–5000 IU dalteparin), medium (> 4500 IU but < 175 IU/kilogram, kg, of body weight tinzaparin or > 5000 IU but < 200 IU/kg of body weight dalteparin), and high dose (≥ 175 IU/kg of body weight tinzaparin or ≥ 200 IU/kg of body weight dalteparin). Thromboprophylaxis dosage was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Cox proportional hazards regression was used to estimate hazard ratios with corresponding 95% confidence intervals of death within 28 days from ICU admission. Multivariable models were adjusted for sex, age, body mass index, Simplified Acute Physiology Score III, invasive respiratory support, and initial dosing strategy of thromboprophylaxis.

Results

A total of 152 patients were included: 67 received low-, 48 medium-, and 37 high-dose thromboprophylaxis. Baseline characteristics did not differ between groups. For patients who received high-dose prophylaxis, mortality was lower (13.5%) compared to those who received medium dose (25.0%) or low dose (38.8%), p = 0.02. The hazard ratio of death was 0.33 (95% confidence intervals 0.13–0.87) among those who received high dose, and 0.88 (95% confidence intervals 0.43–1.83) among those who received medium dose, as compared to those who received low-dose thromboprophylaxis. There were fewer thromboembolic events in the high (2.7%) vs medium (18.8%) and low-dose thromboprophylaxis (17.9%) groups, p = 0.04.

Conclusions

Among critically ill COVID-19 patients with respiratory failure, high-dose thromboprophylaxis was associated with a lower risk of death and a lower cumulative incidence of thromboembolic events compared with lower doses.

Trial registration

Clinicaltrials.gov NCT04412304 June 2, 2020, retrospectively registered.
A novel human laboratory model for screening medications for alcohol use disorder
Authors: Ho Diana , Towns Brandon , Grodin Erica N. , Ray Lara A.
Published: November 2020

Background

Alcohol use disorder (AUD) is a highly prevalent, chronic relapsing disorder with a high disease burden in the USA. Pharmacotherapy is a promising treatment method for AUD; however, the few FDA-approved medications are only modestly effective. Medications development for AUD is a high priority research area, but the cumbersome drug development process hinders many potential compounds from reaching approval. One area with major opportunities for improvement is the process of screening novel compounds for initial efficacy, also known as early phase 2 trials. Early phase 2 trials incorporate human laboratory paradigms to assess relevant clinical constructs, such as craving and subjective responses to alcohol. However, these controlled paradigms often lack the ecological validity of clinical trials. Therefore, early phase 2 trials can be more efficient and clinically meaningful if they combine the internal validity of experimental laboratory testing with the external validity of clinical trials. To that end, the current study aims to develop and validate a novel early efficacy paradigm, informed by smoking cessation literature, to screen novel medications for AUD. As an established AUD medication, naltrexone will serve as an active control to test both the practice quit attempt model and the efficacy of a promising AUD pharmacotherapy, varenicline.

Methods

Individuals with current AUD reporting intrinsic motivation to change their drinking will complete a week-long “practice quit attempt” while on study medication. Participants are randomized and blinded to either naltrexone, varenicline, or placebo. During the practice quit attempt, participants will complete daily visits over the phone and fill out online questionnaires regarding their drinking, alcohol craving, and mood. Additionally, participants will undergo two alcohol cue-reactivity sessions.

Discussion

The successful completion of this study will advance medications development by proposing and validating a novel early efficacy model for screening AUD pharmacotherapies, which in turn can serve as an efficient strategy for making go/no-go decisions as to whether to proceed with clinical trials.

Trial registration

ClinicalTrials.gov NCT04249882. Registered on 31 January 2020.
Postoperative controls of ventilation tubes in children by general practitioner or otolaryngologist? Study protocol for a multicenter randomized non-inferiority study (The ConVenTu study)
Authors: Austad Bjarne , Nilsen Ann Helen , Helvik Anne-Sofie , Albrektsen Grethe , Nordgård Ståle , Thorstensen Wenche Moe
Published: November 2020

Background

Otitis media with effusion is the major cause of acquired hearing problems in children. Some of the affected children need surgery with ventilation tubes in the tympanic membrane to reduce ear complaints and to improve hearing, middle ear function, and health-related quality of life. This is one of the most common ambulatory surgeries performed on children. Postoperative controls are needed to assess that the tubes are functional, to evaluate whether hearing loss has been improved, and to handle potential complications. The follow-up may continue for years and are usually done by otolaryngologists. Nevertheless, there exist no evidence-based guidelines concerning the level of expertise needed for postoperative controls of the ventilation tubes. The aim of this protocol is to describe the ConVenTu study that evaluates whether postoperative controls performed by general practitioners (GPs) represent a safe and sufficient alternative to controls performed by otolaryngologists.

Methods/design

Multicenter randomized non-inferiority study conducted in clinical settings in seven hospitals located in Norway. Discharged children with ventilation tubes, aged 3–10 years, are allocated randomly to receive postoperative controls by either an otolaryngologist at the hospital where they had ventilation tube surgery or their regular GP. Study participants are enrolled consecutively until 200 patients are included in each group. Two years after surgery, we will compare the pure tone average of hearing thresholds (primary endpoint) and middle ear function, complication rate, health-related quality of life and the parents’ evaluations of the postoperative care (secondary endpoints).

Discussion

This protocol describes the first randomized non-inferiority study of GPs performing postoperative controls after surgery with ventilation tubes. Results from this study may be utilized for deriving evidence-based clinical practice guidelines of the level of postoperative controls after ventilation tube surgery which is safe and sufficient.

Trial registration

ClinicalTrials.govNCT02831985. Registered on 13 July 2016
Hemoperfusion with HA380 in acute type A aortic dissection patients undergoing aortic arch operation (HPAO): a randomized, controlled, double-blind clinical trial
Authors: Yang Jing , Ji Dong , Zhu Yue-Qian , Ren Yun , Zhang Xun , Dai Hong-Yu , Sun Xu , Zhou Yi , Chen Zhi-Yuan , Li Qing-Guo , Yao Hao
Published: November 2020

Background

Cardiopulmonary bypass (CPB) is an important cause of significant systemic inflammatory response syndrome (SIRS) in the surgical treatment of acute type A aortic dissection (ATAAD). In patients with arch vessel involvement, extensive surgical repairs often necessitate prolonged use of CPB and results in extensive inflammatory responses. Cytokines and chemokines released during CPB contribute to the progression of SIRS, increase perioperative complications, and negatively impact surgical outcomes. A cytokine adsorber (HA380) is expected to reduce the level of cytokines during CPB, which may decrease both intraoperative and postoperative inflammation. The purpose of this study is to investigate if HA380 is able to reduce the levels of inflammatory cytokines and decrease perioperative complications in ATAAD patients undergoing CPB and deep hypothermic circulatory arrest (DHCA).

Methods

This study is a single-center, randomized, controlled, double-blind clinical trial. The study aims to recruit 88 patients with ATAAD and aortic arch involvement who will undergo CPB and DHCA to repair the dissected aorta. Patients will be randomized equally into the CPB/DHCA only group (control group) and the CPB/DHCA + HA380 hemoperfusion group (intervention group), with 44 patients each. Patients in the control group will undergo CPB and DHCA only, while patients in the intervention group will undergo continuous hemoperfusion with HA380, in addition to CPB and DHCA. The primary outcome is a composite of major perioperative complications. The secondary outcomes include related inflammatory markers, coagulation parameters, and minor perioperative complications. To comprehensively evaluate the effect of hemoperfusion on the perioperative outcomes, we will also determine if there are differences in perioperative all-cause mortality, length of ICU stay, and total hospitalization costs.

Discussion

In the current trial, hemoperfusion will be applied in patients undergoing CPB and DHCA for repair of the aorta involving the aortic arch. This trial aims to test the safety and efficacy of our hemoperfusion device (HA380) in such settings. Upon completion of the trial, we will determine if HA380 is effective in reducing perioperative proinflammatory cytokine levels. Further, we will also verify if reduction in the proinflammatory cytokine levels, if present, translates to improvement in patient outcomes.

Trial registration

ClinicalTrials.govNCT04007484. Registered on 1 July 2019 (retrospectively registered).