bluuebunny/crossref_metadata_2025 huggingface dataset:
Antidepressant-like effects of dezocine in mice: involvement of 5-HT1A and κ opioid receptors
Authors: Shang Li , Duan Cunhao , Chang Shui , Chang Ning , Jia Shushan
Published: June 2021

Dezocine is an opioid with low efficacy at μ-opioid and κ-opioid receptors. It also inhibits the reuptake of norepinephrine and serotonin. Dezocine is an effective analgesic against various clinical painful conditions and is widely used in many Asian countries. Given the unique pharmacology of dezocine, the drug may also have antidepressant-like properties. However, no published preclinical study has explored this possibility. This study examined the potential antidepressant-like activity of dezocine in mice. Male ICR mice were used in the forced swimming test, the tail suspension test, the warm water tail withdrawal test and locomotor activity test to test the effects of dezocine (0.3–3.0 mg/kg). The 5-HT1A receptor antagonist WAY-100635 (1 mg/kg), the μ-opioid receptor antagonist β-funaltrexamine (2 mg/kg) and the κ-opioid receptor agonist U50488 (1 mg/kg) were also studied in combination with dezocine. Dezocine produced a dose-dependent decrease in the immobility time in the forced swimming test and tail suspension test at doses that did not alter the motoric activity as determined in the locomotion test. WAY-100635 and U50488 but not β-funaltrexamine pretreatment significantly blocked the effects of dezocine. Dezocine dose-dependently increased the latency in the tail withdrawal test which was blocked by WAY-100635 and β-funaltrexamine. Combined, these results suggest that dezocine may have antidepressant-like effects. Considering the well-documented analgesic property of dezocine, it may be useful to treat pain and depression comorbidity.
Novel insights into stroke risk beyond resting and maximal bicycle exercise systolic blood pressure
Authors: Mariampillai Julian E. , Prestgaard Erik E. , Kjeldsen Sverre E. , Liestøl Knut , Grundvold Irene , Bodegård Johan , Gjesdal Knut , Erikssen Jan E. , Skretteberg Per T.
Published: June 2021

Objective:

Previous research has shown an association between moderate workload exercise blood pressure (BP) and coronary disease, whereas maximal exercise BP is associated with stroke. We aimed to investigate the association between the increase in BP during maximal exercise and the long-term risk of stroke in healthy, middle-aged men.

Methods:

Two thousand and fourteen men were included in the Oslo Ischemia Study in the 1970s. In the present study, we examined baseline data of the 1392 participants who remained healthy and performed bicycle exercise tests both at baseline and 7 years later. Cox proportional hazard was used to assess the risk of stroke in participants divided into quartiles based on the difference between resting and maximal workload SBP (ΔSBP) at baseline, adjusting for resting BP, age, smoking, serum cholesterol and physical fitness. Follow-up was until the first ischemic or hemorrhagic stroke through 35 years.

Results:

There were 195 incident strokes; 174 (89%) were ischemic. In univariate analyses, there were significant positive correlations between age, resting SBP, resting DBP and SBP at moderate and maximal workload, and risk of stroke. In the multivariate analysis, there was a 2.6-fold (P < 0.0001) increase in risk of stroke in ΔSBP quartile 4 (ΔSBP > 99 mmHg) compared with ΔSBP quartile 2 (ΔSBP 73–85 mmHg), which had the lowest risk of stroke. ΔSBP quartile 1 had a 1.7-fold (P = 0.02) increased risk compared with quartile 2, suggesting a J-shaped association to stroke risk.

Conclusion:

Stroke risk increased with increasing difference between resting and maximal exercise SBP, independent of BP at rest, suggesting that an exaggerated BP response to physical exercise may be an independent predictor of stroke.
Prophylactic Antibiotics Do Not Prevent Infectious Complications of Endoscopic Ultrasound Fine-Needle Aspiration of Pancreatic Cysts
Authors: Palomera-Tejeda Emmanuel , Shah Hassam , Attar Bashar M. , Bhurwal Abhishek , Vohra Ishaan , Mutneja Hemant Raj
Published: June 2021

Despite limited evidence, endoscopic societies recommend routine use of antibiotic prophylaxis for endoscopic ultrasound fine-needle aspiration of pancreatic cystic lesions. Recent studies suggest lack of benefit in this setting. Our objective is to conduct a systematic review and meta-analysis to assess the efficacy of antibiotics in prevention of infectious complications after ultrasound fine-needle aspiration of pancreatic cystic lesions. A bibliographic search of digital dissertation databases was performed from inception until March 2020. Randomized controlled trials, cohort, and case-control studies that compared prophylactic antibiotics with placebo or no therapy were included in the analysis. The primary outcome was the development of cyst infections. Secondary outcomes were incidence of fever; procedural complications such as bile leak, pancreatitis, or bleeding; and medication-related adverse events. Six studies with a total of 1683 patients were included. The overall incidence of cyst infections was 0.53%. For the primary outcome, there was no significant difference between the 2 groups (odds ratio, 0.54; 95% confidence interval, 0.16–1.82; P = 0.32). No significant difference was noted regarding other complications like fever, pancreatitis, or bile leak. In conclusion, the rate of infectious complications is very low, and antibiotic prophylaxis does not seem to confer any additional benefit in their prevention.
Diet and Exercise Interventions in Patients With Pancreatic Cancer
Authors: Kasvis Popi , Kilgour Robert D.
Published: June 2021

Diet and exercise interventions may help reverse malnutrition and muscle wasting common in pancreatic cancer. We performed a scoping review to identify the knowledge gaps surrounding diet and exercise interventions. We searched PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature, Embase, ProQuest Theses and Dissertations, and Google Scholar using the umbrella terms of “pancreatic cancer,” “diet/nutrition,” and “exercise.” Included were articles reporting on ambulatory adults with diagnosed pancreatic cancer. Excluded were studies examining prevention and/or risk, animal, or cell lines. Of the 15,708 articles identified, only 62 met the final inclusion criteria. Almost half of the articles were randomized controlled studies (n = 27). Most studies were from the United States (n = 20). The majority examined dietary interventions (n = 41), with 20 assessing the use of omega-3 fatty acids. Exercise interventions were reported in 13 studies, with 8 examining a diet and exercise intervention. Most studies were small and varied greatly in terms of study design, intervention, and outcomes. We identified 7 research gaps that should be addressed in future studies. This scoping review highlights the limited research examining the effect of diet and exercise interventions in ambulatory patients with pancreatic cancer.
Overt IL-32 isoform expression at intestinal level during HIV-1 infection is negatively regulated by IL-17A
Authors: Moreira Gabriel Etiene , Wiche Salinas Tomas Raul , Gosselin Annie , Larouche-Anctil Etienne , Durand Madeleine , Landay Alan L. , El-Far Mohamed , Tremblay Cécile L. , Routy Jean-Pierre , Ancuta Petronela
Published: June 2021

Objectives:

Untreated HIV infection was previously associated with IL-32 overexpression in gut/intestinal epithelial cells (IEC). Here, we explored IL-32 isoform expression in the colon of people with HIV (PWH) receiving antiretroviral therapy (ART) and IL-32 triggers/modulators in IEC.

Design:

Sigmoid colon biopsies (SCB) and blood were collected from ART-treated PWH (HIV + ART; n = 17; mean age: 56 years; CD4+ cell counts: 679 cells/μl; time on ART: 72 months) and age-matched HIV-uninfected controls (HIVneg; n = 5). The IEC line HT-29 was used for mechanistic studies.

Methods:

Cells from SCB and blood were isolated by enzymatic digestion and/or gradient centrifugation. HT-29 cells were exposed to TLR1–9 agonists, TNF-α, IL-17A and HIV. IL-32α/β/γ/D/ε/θ and IL-17A mRNA levels were quantified by real-time RT-PCR. IL-32 protein levels were quantified by ELISA.

Results:

IL-32β/γ/ε isoform transcripts were detectable in the blood and SCB, with IL-32β mRNA levels being predominantly expressed in both compartments and at significantly higher levels in HIV + ART compared to HIVneg. IL-17A transcripts were only detectable in SCB, with increased IL-17A levels in HIVneg compared with HIV + ART and negatively correlated with IL-32β mRNA levels. IL-32β/γ/ε isoform mRNA were detected in HT-29 cells upon exposure to TNF-α, Poly I:C (TLR3 agonist), Flagellin (TLR-5 agonist) and HIV. IL-17A significantly decreased both IL-32 β/γ/ε mRNA and cell-associated IL-32 protein levels induced upon TNF-α and Poly I:C triggering.

Conclusion:

We document IL-32 isoforms abundant in the colon of ART-treated PWH and reveal the capacity of the Th17 hallmark cytokine IL-17A to attenuate IL-32 overexpression in a model of inflamed IEC.
The entry inhibitor DS003 (BMS-599793): a BMS-806 analogue, provides superior activity as a pre-exposure prophylaxis candidate
Authors: Herrera Carolina , Harman Sarah , Aldon Yoann , Rogers Paul , Armanasco Naomi , Ziprin Paul , Stieh Daniel , Nuttall Jeremy , Shattock Robin J.
Published: June 2021

Objective:

Small molecule inhibitors able to bind to gp120 and prevent CD4+-induced HIV-1 envelope conformational change provide an important class of inhibitors. Currently, only Fostemsavir is approved for HAART, which makes this class of inhibitors attractive candidates for prevention. We assessed the activity of DS003 (BMS-599793), an analogue of BMS-378806, in different mucosal tissues and elucidated its mechanism of action.

Design:

Preclinical analysis was performed with human mucosal tissue models as surrogates of in-vivo activity.

Methods:

Antiviral efficacy of DS003 was assessed in mucosal tissue explants (ecto-cervical, penile and colorectal) and in trans-infection models (co-cultures of dendritic or mucosal migratory cells with CD4+ T cells) with several dosing times (2, 24 h and sustained) and in combination with a fusion inhibitor. Binding of DS003 to gp120 was assessed by flow cytometry and bio-layer interferometry and further probed in competitive studies using soluble CD4+ (sCD4+) and an anti-CD4+ induced antibody, 17b.

Results:

In all models, the inhibitory activity of DS003 was increased with longer periods of exposure and by combination with a fusion inhibitor. Pre-exposure to sCD4+ impeded DS003 binding to viral envelope. In contrast, DS003 did not impact subsequent binding of sCD4+. Furthermore, sCD4+-induced epitope exposure as assessed by 17b binding was significantly reduced in the presence of DS003.

Conclusion:

DS003 inhibits HIV-1 infection by binding to or near the CD4+ binding site of gp120, preventing CD4+-induced conformational change essential for viral fusion. These data highlight the potential of DS003 for development as a pre-exposure prophylaxis candidate.
Epidemiology of Upper-Extremity Amputations Using the National Electronic Injury Surveillance System
Authors: Cramer Jordan , Brown Geoffrey , Herrera Fernando A.
Published: June 2021

Background

Upper-extremity amputations can be devastating injuries that lead to lifelong disabilities. The purpose of our study was to review national data and identify populations at risk and injury patterns that could be targeted with prevention strategies.

Methods

Data from the National Electronic Injury Surveillance System between years 2012 and 2018 were reviewed. Injuries affecting the upper extremity resulting in amputation were included. Patient demographics, anatomical location, mechanism of injury, level of care provided, and setting of injury were recorded. Descriptive was recorded and tabulated for each category.

Results

There were 4,766 patients identified with amputations to the upper extremity from 2012 to 2018. The following categories are listed below: age in years, sex, race, anatomical location of injury, most common mechanisms of injury, disposition of patient, environmental location.

Conclusions

Our data show that male children younger than 10 years are at the high risk for finger amputations. In addition, the majority of these injuries occur in the home. This suggests that safety prevention in the home is a significant area in need of improvement. We recommend further research in areas of home safety and injury prevention to decrease the risk of the devastating injuries.
Modified Carpal Tunnel Release
Authors: Mujadzic Tarik , Friedman Harold I. , Mujadzic Mirza M. , Gober Charles , Chen Elliot , Atwez Abdelaziz , Durkin Martin , Mujadzic Mirsad M.
Published: June 2021

Introduction

Pillar pain is a frequent postoperative complication of carpal tunnel release (CTR). The precise definition of pillar pain is lacking, but most authors describe it as diffuse aching pain and tenderness in the thenar and hypothenar area. The etiology of pillar pain is unclear. However, the most prevalent theory is the neurogenic theory, which attributes the pain to the damage of small nerve branches of palmar cutaneous branches of median nerve after surgical incision, with resulting entrapment of the nerves in the scar tissue at the incision site. We postulated that a main source of pillar pain is sensory neuromas along the incision site.

In this article, we describe a simple modification of the standard CTR technique with intent to decrease neuroma formation and thus minimizing pillar pain.

Materials and Methods

This is a retrospective study comparing the incidence and duration of pillar pain between patients who underwent standard CTR (SCTR, n = 53) versus the minimizing pillar pain CTR technique (n = 55). Based on duration of pillar pain, the groups were placed into 3 subgroups (<3, 3–6, and >6 months). Presence and duration of pillar pain in each group were recorded along with return to work (RTW), complications, and patient satisfaction.

Results

The SCTR group had a total of 17 patients with pillar pain (32.1%), 5 of which resolved within 3 months, 7 within 3 to 6 months, and 5 in more than 6 months. The group that underwent the minimizing pillar pain technique had a total of 4 patients with pillar pain (7.2%). Three resolved within 3 months, 1 resolved within 3 to 6 months, and there were no patients with pillar pain lasting more than 6 months. Average RTW time for minimization of pillar pain CTR (MPPCTR) was 34.9 days. Average RTW time for SCTR was 54.8 days. Satisfaction was higher among patients who underwent surgery with MPPCTR.

Conclusions

Based on these results, we concluded that MPPCTR compared with SCTR had equal complication rate, however, significantly lower incidence and duration of pillar pain, higher rate of satisfaction, and earlier RTW.
Genes implicated inCaenorhabditis elegansand human health regulate stress resistance and physical abilities in agedCaenorhabditis elegans
Authors: Dysarz Jessica , Fuellen Georg , Möller Steffen , Luyten Walter , Schmitz-Linneweber Christian , Saul Nadine
Published: June 2021

Recently, nineCaenorhabditis elegansgenes, grouped into two pathways/clusters, were found to be implicated in healthspan inC. elegansand their homologues in humans, based on literature curation, WormBase data mining and bioinformatics analyses. Here, we further validated these genes experimentally inC. elegans. We downregulated the nine genes via RNA interference (RNAi), and their effects on physical function (locomotion in a swim assay) and on physiological function (survival after heat stress) were analysed in aged nematodes. Swim performance was negatively affected by the downregulation ofacox-1.1,pept-1,pak-2,gsk-3andC25G6.3in worms with advanced age (twelfth day of adulthood) and heat stress resistance was decreased by RNAi targeting ofacox-1.1,daf-22,cat-4,pig-1,pak-2,gsk-3andC25G6.3in moderately (seventh day of adulthood) or advanced aged nematodes. Only one gene,sad-1, could not be linked to a health-related function inC. eleganswith the bioassays we selected. Thus, most of the healthspan genes could be re-confirmed by health measurements in old worms.
Natal origin of Namibian grey whale implies new distance record for in-water migration
Authors: Hoelzel A. Rus , Sarigol Fatih , Gridley Tess , Elwen Simon H.
Published: June 2021

We use genomics to identify the natal origin of a grey whale found in the South Atlantic, at least 20 000 km from the species core range (halfway around the world). The data indicate an origin in the North Pacific, possibly from the endangered western North Pacific population, thought to include only approximately 200 individuals. This contributes to our understanding of Atlantic sightings of this species known primarily from the North Pacific, and could have conservation implications if grey whales have the potential for essentially global dispersion. More broadly, documenting and understanding rare extreme migration events have potential implications for the understanding of how a species may be able to respond to global change.
Separated parabiont reveals the fate and lifespan of peripheral-derived immune cells in normal and ischaemia-induced injured kidneys
Authors: Deng Xuan , Zhou Cheng , Liao Ruichun , Guo Yi , Wang Yuxi , Li Guoli , Wu Jianliang , Xu Huzi , Hu Zhizhi , Pei Guangchang , Liao Wenhui , Yao Ying , Yang Qian , Zeng Rui , Xu Gang
Published: June 2021

Immune cell infiltration plays a key role in acute kidney injury (AKI) to chronic kidney disease (CKD) progression. T lymphocytes, neutrophils, monocytes/macrophages and other immune cells regulate inflammation, tissue remodelling and repair. To determine the kinetics of accumulation of various immune cell populations, we established an animal model combining parabiosis and separation surgery to explore the fate and lifespan of peripheral leucocytes that migrate to the kidney. We found that peripheral T lymphocytes could survive for a long time (more than 14 days), whereas peripheral neutrophils survived for a short time in both healthy and ischaemia-induced damaged kidneys. Nearly half of the peripheral-derived macrophages disappeared after 14 days in normal kidneys, while their existing time in the inflammatory kidneys was prolonged. A fraction of F4/80
high
macrophages were renewed from the circulating monocyte pool. In addition, we found that after renal ischaemia reperfusion, neutrophils increased significantly in the early phase, and T lymphocytes mainly accumulated in the late stage, whereas macrophages infiltrated throughout AKI-CKD progression and were sustained longer in injured as opposed to normal kidneys. In conclusion, peripheral-derived macrophages, T lymphocytes and neutrophils exhibit different lifespans in the kidney, which may play different roles during AKI-CKD progression.
Exploring the therapeutic potential of forkhead box O for outfoxing COVID-19
Authors: Cheema Pradeep Singh , Nandi Deeptashree , Nag Alo
Published: June 2021

The COVID-19 pandemic has wreaked unprecedented societal havoc worldwide. The infected individuals may present mild to severe symptoms, with nearly 20% of the confirmed patients impaired with significant complications, including multi-organ failure. Acute respiratory distress imposed by SARS-CoV-2 largely results from an aggravated cytokine storm and deregulated immune response. The forkhead box O (FoxO) transcription factors are reported to play a significant role in maintaining normal cell physiology by regulating survival, apoptosis, oxidative stress, development and maturation of T and B lymphocytes, secretion of inflammatory cytokines, etc. We propose a potent anti-inflammatory approach based on activation of the FoxO as an attractive strategy against the novel coronavirus. This regime will be focused on restoring redox and inflammatory homeostasis along with repair of the damaged tissue, activation of lymphocyte effector and memory cells. Repurposing FoxO activators as a means to alleviate the inflammatory burst following SARS-CoV-2 infection can prove immensely valuable in the ongoing pandemic and provide a reliable groundwork for enriching our repertoire of antiviral modalities for any such complication in the future. Altogether, our review highlights the possible efficacy of FoxO activation as a novel arsenal for clinical management of COVID-19.
Flavimobilis rhizosphaerae sp. nov., isolated from rhizosphere soil of Spartina alterniflora
Authors: Cai Hanqin , Shi Songbiao , Wu Jiafa , Yang Lifang , Wang Fang , Jiang Chenglin , Gao Caimi , Yang Shaojuan , Jiang Mingguo , Jiang Yi
Published: June 2021

A novel Gram-stain positive, facultatively anaerobic, motile, irregularly rod-shaped bacterium, designated GY 10621T, was isolated from rhizosphere soil ofSpartina alterniflorain Beihai City, Guangxi Province, PR China, and characterized using a polyphasic taxonomic approach. GY 10621Twas positive for catalase and oxidase. Growth occurred at 4–42 °C (optimum 30–37 °C), at pH 5.0–9.0 (optimum pH 7.0) and in the presence of 0–5% NaCl (w/v) (optimum 1–3%). The main menaquinones were MK-9 (H4) (92.2 %) and MK-10 (7.8 %). The major cellular fatty acids were anteiso-C15 : 0and C14 : 0. The peptidoglycan was the type A4α (l-Lys-Ser-d-Glu). The polar lipids included four phosphoglycolipids, four glycolipids, an unidentified lipid and six unidentified phospholipids. The DNA G+C content of the type strain was 71.7 mol%. On the basis of the results of 16S rRNA gene analysis, the type strain of a species with a validly published name with the highest similarity to GY 10621TwasFlavimobilis soliKCTC 13155T(97.16 %), followed bySanguibacter suareziiNBRC 16159T(96.39 %). The calculated results indicated that compared with GY 10621T, the average nucleotide identity (ANI) values of three strains closely related to GY 10621T(the two aforementioned type strains and ‘S. massiliensis’ Marseille-P3815) were 74.18–94.97 %, and the digital DNA–DNA hybridization (dDDH) values were 20.3–60.6 %. The results of 16S rRNA-based and genome-based phylogenetic tree analysis indicated that GY 10621Tshould be assigned to the genusFlavimobilis. On the basis of evidence from polyphasic studies, GY 10621Tshould be designated as representing a novel species of the genusFlavimobilis, for which the nameFlavimobilis rhizosphaeraesp. nov. is proposed. The type strain is GY 10621T(=CGMCC 1.17411T=KCTC 49515T).
Hot water extract of Arthrospira maxima (AHWE) has broad-spectrum antiviral activity against RNA virus including coronavirus SARS-CoV2, and the antivirus spray application
Authors: Chen Yi-Hsiang , Liao Ya-Chun , Huang Jyun-Yuan , Kung Yu-An , Chiueh Chuang-Chun
Published: June 2021

The emergence and re-emergence of RNA virus outbreaks highlight the urgent need for the development of broad-spectrum antiviral agents. Arthrospira maxima has be used as a food source for a long time, and the protein or polysaccharide fractions were evidenced to have antiviral activity, therefore we examined the antiviral efficacy of hot water extract from Arthrospira maxima (AHWE), on Enterovirus 71 (EV71), Influenza virus, Herpes simplex virus (HSV), Respiratory syncytial virus (RSV), Ebola virus, and Coronavirus for antiviral spray application. In this study, we demonstrated that the AHWE shown 90 to 100% inhibition rate on the plaque formation of EV71, HSV-1, HSV-2, influenza virus, RSV, 229E and SARS-COV2 at virus attachment stage, and the long-lasting protection study also found while the AHWE was pre-exposed to the open air for more than 4 hours in plaque reduction assay. In addition, AHWE also had inhibitory effect on Ebola virus replication at 500 ug/ml. Finally, AHWE also shown no toxicity and skin sensitivity that imply it could be safe for future clinical use if approved by FDA. In conclusion, this study suggests that AHWE could be developed as a potential broad-spectrum antivirus spray product and therapeutic agent.
Development of methods for purification of individual biological active substances obtained from extracts of Hedysarum neglectum
Authors: Dmitrieva Anastasia Igorevna , Drozdova Margarita Yuryevna , Dolganyuk Vyacheslav Fedorovich
Published: June 2021

Hedysarum neglectum is a forage plant. Xanthone glycoside - mangiferin is extracted from this plant and used for medicine “Alpizarin”. In addition to substances of xanthone nature (mangiferin and isomangiferin) Hedysarum neglectum contains sugars, vitamins and provitamins, tannins; in the underground part it contains oligomeric catechins, isoflavonoids, butylphenols, alkaloids, tannins, flavonoids, saponins, coumarins, carbohydrates, vitamin C. For selecting optimal schemes of fractionization of substances, it is necessary to resort to multi-stage schemes of group-wide (preliminary) isolation and preparative accumulation. In particular cases, it is necessary to take into account the presence of concomitant substances, as well as the effectiveness and selectivity of the sorption-chromatographic technologies used. According to the results of the studies, the use of silica gel and sefadex LH-20 for the isolation of a complex of flavonoids and gallic acid is the most effective method for the selection of the optimal variant of the preparative isolation of the total amount of BAS in mcg/ml. The results of the research allowed us to identify the target biologically active substances with a degree of extraction of at least 80%: - fractions of xanthones, flavonoids, gallic acid.
Modern contraceptive use among adolescent girls and young women in Benin: a mixed-methods study
Authors: Adelphe Ahissou Noudéhouénou Crédo , Benova Lenka , Delvaux Thérèse , Gryseels Charlotte , Dossou Jean-Paul , Goufodji Sourou , Kanhonou Lydie , Boyi Christelle , Vigan Armelle , Peeters Koen , Sato Miho , Matsui Mitsuaki
Published: June 2021

Objectives

The study aimed to assess the determinants of modern contraceptive method use among young women in Benin.

Design

A mixed-methods design.

Setting and participants

We used the Benin 2017-18 Demographic and Health Survey datasets for quantitative analysis. Data collection was conducted using multiple-cluster sampling method and through household survey. Qualitative part was conducted in the city of Allada, one of the Fon cultural capitals. The participants were purposively selected.

Outcomes

Contraceptive prevalence rate, unmet need for modern method, and percentage of demand satisfied by a modern method for currently married and sexually active unmarried women were measured in the quantitative part. Access barriers and utilization of modern methods were assessed in the qualitative part.

Results

Overall, 8.5% (95%CI: 7.7-9.5%) among young women ages 15 to 24 were using modern contraceptives and 13% (95%CI: 12.1-14.0%) among women ages 25 or more. Women 15-24 had a higher unmet need, and a lower demand satisfied by modern contraceptive methods compared to women aged 25 or more. 60.8% (56.9-64.7%) of all unmarried young women had unmet need for modern contraceptives. Young women were more likely to use male condoms which they obtain mainly from for-profit outlets, pharmacies, and relatives. The factors associated with demand satisfied by a modern method were literacy, being unmarried, knowing a greater number of modern contraceptive methods, and experiencing barriers in access to health services. On the other hand, the qualitative study found that barriers to using modern methods include community norms about pre-marital sexual intercourse, perceptions about young women’s fertility, spousal consent, and the use of non-modern contraceptives.

Conclusion

Contraceptive use is low among young women in Benin. The use of modern contraceptives is influenced by socio-demographic factors and social norms. Appropriate interventions might promote comprehensive sexuality education, increase community engagement, provide youth-friendly services, and address gender inequalities.

Strengths and limitations of this study

This study used a nationally representative survey data which allows generalizability at the national level.

We used a mixed methods design which enables us to compare and discuss the large-scale quantitative data with qualitative information from the ground.

The quantitative information could have been affected by recall errors and biases.
“We felt like part of a production system”: a qualitative study on women’s experience of mistreatment during childbirth in Switzerland
Authors: Meyer Stephanie , Cignacco Eva , Monteverde Settimio , Trachsel Manuel , Raio Luigi , Oelhafen Stephan
Published: June 2021

Introduction

Mistreatment during childbirth is an issue of global magnitude that not only violates fundamental human rights but also seriously impacts women’s well-being. The purpose of this study was to gain a better understanding of the phenomenon by exploring the individual experiences of women who reported mistreatment during childbirth in Switzerland.

Materials and Methods

This project used a mixed methods approach to investigate women’s experiences of mistreatment during childbirth in general and informal coercion specifically: the present qualitative study expands on the findings from a nationwide online survey on childbirth experience. It combines inductive with theory-guided thematic analysis to study the 7753 comments women wrote in the survey and the subsequent interviews with 11 women who reported being mistreated during childbirth.

Results

The women described a wide range of experiences of mistreatment during childbirth in both the survey comments and the interviews. Out of all survey participants who wrote at least one comment (n = 3547), 28% described one or more experiences of mistreatment. Six of the seven types of mistreatment listed in Bohren and colleagues’ typology of mistreatment during childbirth were found, the most frequent of which were ineffective communication and lack of informed consent. Five further themes were identified in the interviews: informal coercion, risk factors for mistreatment, consequences of mistreatment, examples of good care, and what’s needed to improve maternity care.

Conclusion

The findings from this study show that experiences of mistreatment are a reality in Swiss maternity care and give insight into women’s individual experiences as well as how these affect them during and after childbirth. This study emphasises the need to respect women’s autonomy in order to prevent mistreatment and empower women to actively participate in decisions. Both individual and systemic efforts are required to prevent mistreatment and guarantee respectful, dignified, and high-quality maternity care for all.
Cell culture-based production of defective interfering influenza A virus particles in perfusion mode using an alternating tangential flow filtration system
Authors: Hein Marc D. , Chawla Anshika , Cattaneo Maurizio , Kupke Sascha Y. , Genzel Yvonne , Reichl Udo
Published: June 2021

Respiratory diseases including influenza A virus (IAV) infections represent a major threat to human health. While the development of a vaccine requires a lot of time, a fast countermeasure could be the use of defective interfering particles (DIPs) for antiviral therapy. IAV DIPs are usually characterized by a large internal deletion in one viral RNA segment. Consequentially, DIPs can only propagate in presence of infectious standard viruses (STVs), compensating the missing gene function. Here, they interfere with and suppress the STV replication and might act “universally” against many IAV subtypes. We recently reported a production system for purely clonal DIPs utilizing genetically modified cells. In the present study, we established an automated perfusion process for production of a DIP, called DI244, using an alternating tangential flow filtration (ATF) system for cell retention. Viable cell concentrations and DIP titers more than 10-times higher than for a previously reported batch cultivation were observed. Further, we investigated a novel tubular cell retention device for its potential for continuous virus harvesting into the permeate. Very comparable performances to typically used hollow fiber membranes were found during the cell growth phase. During the virus replication phase the tubular membrane, in contrast to the hollow fiber membrane, allowed 100% of the produced virus particles to pass through. To our knowledge, this is the first time a continuous virus harvest was shown for a membrane-based perfusion process. Overall, the process established offers interesting possibilities for advanced process integration strategies for next-generation virus particle and virus vector manufacturing.

Key points

An automated perfusion process for production of IAV DIPs was established

DIP titers of 7.40E+9 plaque forming units per mL were reached

A novel tubular cell retention device enabled continuous virus harvesting
Compensatory CSF2-driven macrophage activation promotes adaptive resistance to CSF1R inhibition in breast-to-brain metastasis
Authors: Klemm Florian , Schäffer Alexander , Salamero-Boix Anna , Alekseeva Tijna , Schulz Michael , Niesel Katja , Maas Roeltje R. , Groth Marie , Elie Benelita T. , Bowman Robert L. , Hegi Monika E. , Daniel Roy T. , Zeiner Pia S. , Zinke Jenny , Harter Patrick N. , Plate Karl H. , Joyce Johanna A. , Sevenich Lisa
Published: June 2021

Tumor microenvironment-targeted therapies are emerging as promising treatment options for different cancer types. Tumor-associated macrophages and microglia (TAMs) represent an abundant non-malignant cell type in brain metastases and have been proposed to modulate metastatic colonization and outgrowth. We used an inhibitor of colony stimulating factor 1 receptor (CSF1R) to target TAMs at distinct stages of the metastatic cascade in preclinical breast-to-brain metastasis models and found that CSF1R inhibition leads to anti-tumor responses in prevention and intervention trials. However, in established brain metastases, compensatory CSF2Rb-STAT5-mediated pro-inflammatory TAM activation blunted the ultimate efficacy of CSF1R inhibition by inducing neuro-inflammation gene signatures in association with wound repair responses that fostered tumor recurrence. Consequently, combined blockade of CSF1R and STAT5 signaling led to sustained tumor control, a normalization of microglial activation states and amelioration of neuronal damage.
Dual roles of a novel oncolytic viral vector-based SARS-CoV-2 vaccine: preventing COVID-19 and treating tumor progression
Authors: Sun Yaping , Dong Wenjuan , Tian Lei , Rao Youliang , Qin Chao , Jaramillo Sierra A. , Settles Erik W. , Ma Shoubao , Zhang Jianying , Yu Kang , Xu Bo , Yan Jiazhuo , Ma Rui , Li Zhuo , Dadwal Sanjeet S. , Barker Bridget M. , Keim Paul S. , Feng Pinghui , Caligiuri Michael A. , Yu Jianhua
Published: June 2021

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer patients are usually immunocompromised and thus are particularly susceptible to SARS-CoV-2 infection resulting in COVID-19. Although many vaccines against COVID-19 are being preclinically or clinically tested or approved, none have yet been specifically developed for cancer patients or reported as having potential dual functions to prevent COVID-19 and treat cancer. Here, we confirmed that COVID-19 patients with cancer have low levels of antibodies against the spike (S) protein, a viral surface protein mediating the entry of SARS-CoV-2 into host cells, compared with COVID-19 patients without cancer. We developed an oncolytic herpes simplex virus-1 vector-based vaccine named oncolytic virus (OV)-spike. OV-spike induced abundant anti-S protein neutralization antibodies in both tumor-free and tumor-bearing mice, which inhibit infection of VSV-SARS-CoV-2 and wild-type (WT) live SARS-CoV-2 as well as the B.1.1.7 variant in vitro. In the tumor-bearing mice, OV-spike also inhibited tumor growth, leading to better survival in multiple preclinical tumor models than the untreated control. Furthermore, OV-spike induced anti-tumor immune response and SARS-CoV-2-specific T cell response without causing serious adverse events. Thus, OV-spike is a promising vaccine candidate for both preventing COVID-19 and enhancing the anti-tumor response.

One Sentence Summary

A herpes oncolytic viral vector-based vaccine is a promising vaccine with dual roles in preventing COVID-19 and treating tumor progression
Constitutive AP2γ deficiency reduces postnatal hippocampal neurogenesis and induces behavioral deficits in juvenile mice that persist during adulthood
Authors: Loureiro-Campos Eduardo , Alves Nuno Dinis , Mateus-Pinheiro António , Patrício Patrícia , Soares-Cunha Carina , Silva Joana , Sardinha Vanessa Morais , Mendes-Pinheiro Bárbara , Silveira-Rosa Tiago , João Rodrigues Ana , Oliveira João Filipe , Sousa Nuno , Pinto Luísa
Published: June 2021

The transcription factor activating protein two gamma (AP2γ) is an important regulator of neurogenesis both during embryonic development as well as in the postnatal brain, but its role for neurophysiology and behavior at distinct postnatal periods is still unclear. In this work, we explored the neurogenic, behavioral, and functional impact of a constitutive AP2γ heterozygous deletion in mice from early postnatal development until adulthood. Constitutive AP2γ heterozygous deletion in mice caused a reduction of hippocampal transient amplifying progenitors (TAPs) in the postnatal brain, inducing significant impairments on hippocampal-dependent emotional- and cognitive-behavioral tasks including anxiety-like behavior and cognitive deficits, typically associated with an intact neurogenic activity. Moreover, AP2γ deficiency impairs dorsal hippocampus-to-prefrontal cortex functional connectivity.

We observed a progressive and cumulative impact of constitutive AP2γ deficiency on the hippocampal glutamatergic neurogenic process, as well as alterations on limbic-cortical connectivity, together with impairments on emotional and cognitive behaviors from juvenile to adult periods. Collectively, the results herein presented demonstrate the importance of AP2γ in the generation of glutamatergic neurons in the postnatal brain and its impact on behavioral performance.
Hepatic MIR20B promotes nonalcoholic fatty liver disease by suppressing PPARA
Authors: Lee Yo Han , Jang Hyun-Jun , Kim Sounkou , Choi Sun Sil , Khim Keon Woo , Eom Hye-Jin , Hyun Jimin , Shin Kyeong Jin , Chae Young Chan , Kim Hongtae , Park Jiyoung , Park Neung Hwa , Woo Chang-Yun , Hong Chung Hwan , Koh Eun Hee , Nam Dougu , Choi Jang Hyun
Published: June 2021

Background

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and imbalances in lipid metabolism in the liver. Although nuclear receptors (NRs) play a crucial role in hepatic lipid metabolism, the underlying mechanisms of NR regulation in NAFLD remain largely unclear.

Methods

Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in human NAFLD patients, we revealed that MIR20B specifically targets PPARA. MIR20B mimic and anti-MIR20B were administered to human HepG2 and Huh-7 cells and mouse primary hepatocytes as well as high fat diet (HFD)- or methionine-deficient diet (MCD)-fed mice to verify the specific function of MIR20B in NAFLD. We tested the inhibition of the therapeutic effect of a PPARα agonist, fenofibrate, by MIR20B and the synergic effect of combination of fenofibrate with anti-MIR20B.

Results

We revealed that MIR20B specifically targets PPARA through miRNA regulatory network analysis of nuclear receptor genes in NAFLD. The expression of MIR20B was upregulated in free fatty acid (FA)- treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of MIR20B significantly increased hepatic lipid accumulation and triglyceride levels. Furthermore, MIR20B significantly reduced FA oxidation and mitochondrial biogenesis by targeting PPARA. In MIR20B-introduced mice, the effect of fenofibrate to ameliorate hepatic steatosis was significantly suppressed. Finally, inhibition of MIR20B significantly increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Moreover, combination of fenofibrate and anti-MIR20B exhibited the synergic effect on improvement of NAFLD in MCD-fed mice.

Conclusions

Taken together, our results demonstrate that the novel MIR20B targets PPARA, plays a significant role in hepatic lipid metabolism, and present an opportunity for the development of novel therapeutics for NAFLD.

Funding

This research was funded by Korea Mouse Phenotyping Project (2016M3A9D5A01952411), the National Research Foundation of Korea (NRF) grant funded by the Korea government (2020R1F1A1061267, 2018R1A5A1024340, NRF-2021R1I1A2041463, 2020R1I1A1A01074940), and the Future-leading Project Research Fund (1.210034.01) of UNIST.
FETCH: A platform for high-throughput quantification of gap junction hemichannel docking
Authors: Ransey Elizabeth , Chesnov Kirill , Bursac Nenad , Dzirasa Kafui
Published: June 2021

Gap junctions are membrane spanning channels that connect the cytoplasm of apposed cells, allowing for the passage of small molecules and ions. They are formed by the connexin (Cx) family of proteins which assemble into hexameric hemichannels on each cell and dock to create gap junctional channels between two cells. Despite importance of various Cx isoforms in human physiology and disease, available tools for screening and discriminating their interactions such as hemichannel compatibility, docking and permeability are limited. Here, we developed FETCH (flow enabled tracking of connexosomes in HEK cells), a method which utilizes the generation of annular gap junctions (connexosomes) as downstream indicators of hemichannel compatibility for intercellular docking. First, we show that fluorescent connexosomes create a cellular phenotype that is detectable by flow cytometry analysis. We then show that FETCH identifies homotypic and heterotypic docking of many single isoform connexin hemichannels. Finally, we demonstrate that FETCH captures the impact of disease-relevant connexin protein mutations on gap junction formation. Thus, we establish a new flow cytometry-based method that is amenable to the high-throughput classification of gap junction hemichannel docking.
Cannabinoids vs. whole metabolome: relevance of cannabinomics in analyzing Cannabis varieties
Authors: Vásquez-Ocmín Pedro G. , Marti Guillaume , Bonhomme Maxime , Mathis Fabienne , Fournier Sylvie , Bertani Stéphane , Maciuk Alexandre
Published: June 2021

Cannabis sativa has a long history of domestication both for its bioactive compounds and its fibers. This has produced hundreds of varieties, usually characterized in the literature by chemotypes, with Δ9-THC and CBD content as the main markers. However, chemotyping could also be done based on minor compounds (phytocannabinoids and others). In this work, a workflow, which we propose to name cannabinomics, combines mass spectrometry of the whole metabolome and statistical analysis to help differentiate C. sativa varieties and deciphering their characteristic markers. By applying this cannabinomics approach to the data obtained from 20 varieties of C. sativa (classically classified as chemotype I, II, or III), we compared the results with those obtained by a targeted quantification of 11 phytocannabinoids. Cannabinomics can be considered as a complementary tool for phenotyping and genotyping, allowing the identification of minor compounds playing a key role as markers of differentiation.
Towards the Myoelectric Digital Twin: Ultra Fast and Realistic Modelling for Deep Learning
Authors: Maksymenko Kostiantyn , Clarke Alexander Kenneth , Guerra Irene Mendez , Deslauriers-Gauthier Samuel , Farina Dario
Published: June 2021

Muscle electrophysiology has emerged as a powerful tool to drive human machine interfaces, with many new recent applications outside the traditional clinical domains. It is currently a crucial component of control systems in robotics and virtual reality. However, more sophisticated, functional, and robust decoding algorithms are required to meet the fine control requirements of these new applications. Deep learning approaches have shown the highest potential in this regard. To be effective, deep learning requires a large amount of high-quality annotated data for training; the only option today is the use of experimental electromyography data. Yet the acquisition and labelling of training data is time-consuming and expensive. Moreover, the high-quality annotation of this data is often not possible because the ground truth labels are hidden. Data augmentation using simulations, a strategy applied in other deep learning applications, has never been attempted in electromyography due to the absence of computationally efficient and realistic models. Here, we present a new highly realistic and ultra-fast computational model tailored for the training of deep learning algorithms. For the first time, we are able to simulate arbitrary large datasets of realistic electromyography signals with high internal variability and leverage it to train deep learning algorithms. Because the computational model provides access to all the hidden parameters of the simulation, it also allows us to use some annotation strategies that are impossible with experimental data. We believe that this concept of Myoelectric Digital Twin allows new unprecedented approaches to muscular signals decoding and will accelerate the development of human-machine interfaces.
T helper 2 transcriptional profile predicts single-cell HIV envelope-specific polyfunctional CD4+ T cells correlated with reduced risk of infection in RV144 trial
Authors: Cohen Kristen W. , Tian Yuan , Thayer Casey , Seese Aaron , Amezquita Robert , McElrath M. Juliana , De Rosa Stephen C. , Gottardo Raphael
Published: June 2021

Despite the critical role antigen-specific T cells play in responding to viral infections, their aggregate frequencies in peripheral blood have not correlated with clinical protection during HIV infection. However, a subset of HIV-specific CD4+ T cells, termed polyfunctional T cells, can produce multiple effector cytokines simultaneously. In the RV144 HIV vaccine trial, polyfunctional T cells correlated with reduced risk of HIV infection. Little is known about what differentiates polyfunctional T cells from other vaccine-elicited T cells. Therefore, we developed a novel live-cell multiplexed cytokine capture assay, to identify and transcriptionally profile vaccine-specific polyfunctional CD4+ T cells. We applied these methods to samples from the HVTN 097 clinical trial of the same vaccine regimen as RV144. We discovered two surface receptors that were enriched among polyfunctional CD4+ T cells and a Th2-biased signature (IL-4, IL-5, and IL-13) that specifically predicted the envelope-specific polyfunctional CD4+ T cells that were correlated with reduced risk of HIV infection in RV144. By linking single-cell transcriptional and functional profiles, we may be able to further define the role of vaccine-elicited polyfunctional T cells in contributing to effective immunity.

Key Points

Novel ex vivo multiplexed cytokine capture assay to enumerate and single-cell sort polyfunctional T cells for downstream analyses

Polyfunctional T cells were specifically detected among the HIV envelope-stimulated CD4+ T cells

Single-cell RNA sequencing identified novel surface markers enriched among vaccine-specific polyfunctional CD4+ T cells

Th2 transcriptional signature predicted polyfunctional CD4+ T cell profile that had correlated with reduced risk of HIV infection in the RV144 HIV efficacy trial