bluuebunny/crossref_metadata_2025 huggingface dataset:
Health promotion focusing on migrant women through a community based participatory research approach
Authors: Lindsjö Cecilia , Sjögren Forss Katarina , Kumlien Christine , Rämgård Margareta
Published: October 2021

Background

Migrants are often more vulnerable to health issues compared to host populations, and particularly the women. Therefore, migrant women’s health is important in promoting health equity in society. Participation and empowerment are central concepts in health promotion and in community-based participatory research aimed at enhancing health. The aim of this study was to identify conditions for health promotion together with women migrants through a community-based participatory research approach.

Methods

A community-based participatory research approach was applied in the programme Collaborative Innovations for Health Promotion in a socially disadvantaged area in Malmö, Sweden, where this study was conducted.
Residents in the area were invited to participate in the research process on health promotion. Health promoters were recruited to the programme to encourage participation and a group of 21 migrant women participating in the programme were included in this study. A qualitative method was used for the data collection, namely, the story-dialogue method, where a process involving issue, reflections and actions guided the dialogues. The material was partly analysed together with the women, inspired by the second-level synthesis.

Results

Two main health issues, mental health and long-term pain, were reflected upon during the dialogues, and two main themes were elaborated in the process of analysis: Prioritising spare time to promote mental health and Collaboration to address healthcare dissatisfaction related to long-term pain. The women shared that they wanted to learn more about the healthcare system, and how to complain about it, and they also saw the togetherness as a strategy along the way. A decision was made to start a health circle in the community to continue collaboration on health promotion.

Conclusions

The community-based participatory research approach and the story dialogues constituted an essential foundation for the empowerment process. The health circle provides a forum for further work on conditions for health promotion, as a tool to support migrant women’s health.
Presumed post-mortem donors: the degree of information among university students
Authors: da Silva Clemente Pinho Rita , Nogueira da Costa Santos Cristina Maria , Resende Figueiredo Duarte Ivone Maria
Published: October 2021

Background

Organ transplantation represents the most effective and acceptable therapy for end-stage organ failure. However, its frequent practice often leads to a shortage of organs worldwide. To solve this dilemma, some countries, such as Portugal, have switched from an opt-in to an opt-out system, which has raised concerns about respect for individual autonomy. We aimed to evaluate whether young university students are aware of this opt-out system so that they can make informed, autonomous and conscious decisions, as well as to identify the factors that determine a positive attitude toward post-mortem organ donation.

Methods

An observational, cross-sectional study was developed and a questionnaire was administered to first-year students from six faculties of the University of Porto.

Results

Of the 841 participants, 60% were unaware that Portugal had adopted an opt-out system. Among the informed individuals, their main sources of information included social media, internet, and family. Furthermore, only 48% of all participants agreed with the current opt-out system. Female sex (p = 0.049; OR 1.393), knowledge of the law (p < 0.001; OR 4.749) and family being the primary source of information (p < 0.001; OR 2.855) were independent factors associated with a positive attitude toward post-mortem organ donation law.

Conclusions

There is a significant lack of knowledge among young university students regarding the presumed post-mortem organ donation law and how it works. Female sex, having family as a primary source of information and being aware of the presumed post-mortem organ donation law are the strongest independent factors that determine a positive attitude toward the opt-out system.
Estimated impact of COVID-19 on preventive care service delivery: an observational cohort study
Authors: Laing Scott , Johnston Sharon
Published: October 2021

Background

COVID-19 has caused significant healthcare service disruptions. Surgical backlogs have been estimated but not for other healthcare services. This study aims to estimate the backlog of preventive care services caused by COVID-19.

Methods

This observational study assessed preventive care screening rates at three primary care clinics in Ottawa, Ontario from March to November 2020 using data from 22,685 electronic medical records. The change in cervical cancer, colorectal cancer, and type 2 diabetes screening rates were crudely estimated using 2016 census data, estimating the volume of key services delayed by COVID-19 across Ontario and Canada.

Results

The mean percentage of patients appropriately screened for cervical cancer decreased by 7.5% (− 0.3% to − 14.7%; 95% CI), colorectal cancer decreased by 8.1% (− 0.3% to − 15.8%; 95% CI), and type 2 diabetes decreased by 4.5% (− 0.2% to − 8.7%; 95% CI). Crude estimates imply 288,000 cervical cancer (11,000 to 565,000; 95% CI), 326,000 colorectal cancer (13,000 to 638,000; 95% CI), and 274,000 type 2 diabetes screenings (13,000 to 535,000; 95% CI) may be overdue in Ontario. Nationally the deficits may be tripled these numbers. Re-opening measures have not reversed these trends.

Interpretation

COVID-19 decreased the delivery of preventive care services, which may cause delayed diagnoses, increased mortality, and increased health care costs. Virtual care and reopening measures have not restored the provision of preventive care services. Electronic medical record data could be leveraged to improve screening via panel management. Additional, system-wide primary care and laboratory capacity will be needed to restore pre-COVID-19 screening rates.
Quality of care and patient safety at healthcare institutions in Oman: quantitative study of the perspectives of patients and healthcare professionals
Authors: Al-Jabri Fatma , Kvist Tarja , Sund Reijo , Turunen Hannele
Published: October 2021

Background

Oman’s healthcare system has rapidly transformed in recent years. A recent Report of Quality and Patient Safety has nevertheless highlighted decreasing levels of patient safety and quality culture among healthcare professionals. This indicates the need to assess the quality of care and patient safety from the perspectives of both patients and healthcare professionals.

Objectives

This study aimed to examine (1) patients’ and healthcare professionals’ perspectives on overall quality of care and patient safety standards at two tertiary hospitals in Oman and (2) which demographic characteristics are related to the overall quality of care and patient safety.

Methods

A cross-sectional study design was employed. Data were collected by two items: overall quality of care and patient safety, incorporated in the Revised Humane Caring Scale, and Healthcare Professional Core Competency Instrument. Questionnaires were distributed to (1) patients (n = 600) and (2) healthcare professionals (nurses and physicians) (n = 246) in three departments (medical, surgical and obstetrics and gynaecology) at two tertiary hospitals in Oman towards the end of 2018 and the beginning of 2019. Descriptive statistics and binary logistic regression were used for data analysis.

Results

A total of 367 patients and 140 healthcare professionals completed the questionnaires, representing response rates of 61.2% and 56.9%, respectively. Overall, quality of care and patient safety were perceived as high, with the healthcare professionals rating quality of care (M = 4.36; SD = 0.720) and patient safety (M = 4.39; SD = 0.675) slightly higher than the patients did (M = 4.23; SD = 0.706), (M = 4.22; SD = 0.709). The findings indicated an association between hospital variables and overall quality of care (OR = 0.095; 95% CI = 0.016–0.551; p = 0.009) and patient safety (OR = 0.153; 95% CI = 0.027–0.854; p = 0.032) among healthcare professionals. Additionally, an association between the admission/work area and participants’ perspectives on the quality of care (patients, OR = 0.257; 95% CI = 0.072–0.916; p = 0.036; professionals, OR = 0.093; 95% CI = 0.009–0.959; p = 0.046) was found.

Conclusions

The perspectives of both patients and healthcare professionals showed that they viewed both quality of care and patient safety as excellent, with slight differences, indicating a high level of patient satisfaction and competent healthcare delivery professionals. Such perspectives can provide meaningful and complementary insights on improving the overall standards of healthcare delivery systems.
The provider’s checklist to improve pregnant women coverage by intermittent preventive malaria treatment in Mali: a pilot implementation study
Authors: Doumbia Issa , Seydou Fomba , Diakalia Koné , Bennis Issam
Published: October 2021

Background

Intermittent preventive treatment of malaria in pregnancy (IPTp) is a comprehensive treatment protocol of anti-malarial drugs administered to pregnant women to prevent malaria, started at the fourth pregnancy month, with at least three doses of sulfadoxine–pyrimethamine (SP), taken as directly observed treatment (DOT) every 30 days at intervals until childbirth, in combination with other preventive measures. This paper introduces feasibility and adoption concepts as implementation research outcomes (IRO), allowing after a defined intervention, to assess the coverage improvement by IPTp for women attending a reference district hospital in Mali. Specifically, the purpose is to evaluate the feasibility of a reminder tool (provider checklist) to enhance pregnant women’s adoption of information about IPTp-SP uptake as immediate and sustained women practices.

Methods

The implementation strategy used a reminder checklist about malaria knowledge and the recommended preventive tools. Then, the checklist feasibility was assessed during routine practices with the adoption-level about pregnant women’ knowledge. Quantitative data were collected through a questionnaire distributed to a non-probability purposive sampling targeting 200 pregnant women divided into two groups before and after the checklist intervention. In contrast, the qualitative data were based on in-depth face-to-face gynaecologists’ interviews.

Results

Both the IROs (feasibility and adoption) were satisfactory. The gynaecologists agreed to the use of this checklist during routine practice with a recommendation to generalize it to other health providers. After a gynaecologist visit, a significant increase of the adoption-level about prior knowledge and preventive tools was noticed. A total of 83% of participants were not knowledgeable about malaria disease before checklist use versus 15% after. Similarly, coverage of women’s SP DOT rose from 0 to 59% after introducing the checklist and the IPTp-SP uptake after the visit was highly significant in the second group. The latter reached 95% of pregnant women with 4–8 months’ gestational age, that mostly respected all SP future visits as theoretically scheduled.

Conclusions

Generalizing such a checklist reminder will improve women’s knowledge about malaria prevention.
Entomological survey in two communes with residual malaria transmission in Gia Lai Province in the central highlands of Vietnam
Authors: Nguyen Thai Quang , Nguyen Manh Duc , Pham Vinh Xuan , Ro Huan Mah , Edstein Michael D. , Chow Weng K. , Martin Nicholas J. , Hertz Jeffrey C. , Motoki Maysa T.
Published: October 2021

Background

In 2018, the National Malaria Control Programme in Vietnam switched from prioritizing malaria control to elimination. However, with the ongoing elimination programme, there are still areas where residual malaria transmission persists, including the central highlands. This entomological survey was conducted to evaluate Anopheles diversity and host-seeking activity of Anopheles vectors in two communes with very low malaria transmission in Gia Lai Province.

Methods

Anopheles species were collected in Ia DReh commune and Ia KDam commune, Gia Lai Province in the central highlands of Vietnam. Collections were conducted using human-baited double net trap, light trap and manual aspiration collections around cattle sheds, in the dry and rainy season. Mosquito specimens were identified morphologically, and members of species complexes were distinguished molecularly. Mosquito night-feeding patterns were investigated during the dry and rainy seasons.

Results

Overall, 18,835 specimens including 19 taxa were collected in Ia KDam and Ia DReh communes. These included the primary malaria vectors, Anopheles dirus and Anopheles minimus, and other secondary vector species. Anopheles dirus was observed to be an anthropophilic species, whereas An. minimus and a number of secondary vectors were observed to be zoophilic. Anopheles vagus was the dominant species, followed by Anopheles sinensis and Anopheles peditaeniatus. The majority of specimens were collected in the rainy season due to the relatively large number of An. vagus, while An. peditaeniatus, An. dirus, Anopheles kochi, Anopheles monstrosus and Anopheles tessellatus were collected in greater numbers during the dry season. The peak of host-seeking activity for An. dirus, An. sinensis, and An. vagus was between 18.00 and 19.00 h.

Conclusion

This study provided information on the diversity, seasonal prevalence and behaviour of Anopheles at the study sites. Identifying the diverse mosquito fauna in the central highlands of Vietnam allows species-specific control measures to be implemented by the National Programme to reduce malaria in areas of very low malaria transmission. The peak Anopheles host-seeking activity observed in this study was between 18.00 and 23.00 h, which highlights the need to better characterize Anopheles behaviour in this region of Vietnam to inform on vector control strategies.
Intraoperative serosal extracellular mapping of the human distal colon: a feasibility study
Authors: Lin Anthony Y. , Varghese Chris , Du Peng , Wells Cameron I. , Paskaranandavadivel Niranchan , Gharibans Armen A. , Erickson Jonathan C. , Bissett Ian P. , O’Grady Greg
Published: October 2021

Background

Cyclic motor patterns (CMP) are the predominant motor pattern in the distal colon, and are important in both health and disease. Their origin, mechanism and relation to bioelectrical slow-waves remain incompletely understood. During abdominal surgery, an increase in the CMP occurs in the distal colon. This study aimed to evaluate the feasibility of detecting propagating slow waves and spike waves in the distal human colon through intraoperative, high-resolution (HR), serosal electrical mapping.

Methods

HR electrical recordings were obtained from the distal colon using validated flexible PCB arrays (6 × 16 electrodes; 4 mm inter-electrode spacing; 2.4 cm2, 0.3 mm diameter) for up to 15 min. Passive unipolar signals were obtained and analysed.

Results

Eleven patients (33–71 years; 6 females) undergoing colorectal surgery under general anaesthesia (4 with epidurals) were recruited. After artefact removal and comprehensive manual and automated analytics, events consistent with regular propagating activity between 2 and 6 cpm were not identified in any patient. Intermittent clusters of spike-like activities lasting 10–180 s with frequencies of each cluster ranging between 24 and 42 cpm, and an average amplitude of 0.54 ± 0.37 mV were recorded.

Conclusions

Intraoperative colonic serosal mapping in humans is feasible, but unlike in the stomach and small bowel, revealed no regular propagating electrical activity. Although sporadic, synchronous spike-wave events were identifiable. Alternative techniques are required to characterise the mechanisms underlying the hyperactive CMP observed in the intra- and post-operative period.

New findings

The aim of this study was to assess the feasibility of detecting propagating electrical activity that may correlate to the cyclic motor pattern in the distal human colon through intraoperative, high-resolution, serosal electrical mapping. High-resolution electrical mapping of the human colon revealed no regular propagating activity, but does reveal sporadic spike-wave events. These findings indicate that further research into appropriate techniques is required to identify the mechanism of hyperactive cyclic motor pattern observed in the intra- and post-operative period in humans.
Light at night and risk of breast cancer: a systematic review and dose–response meta-analysis
Authors: Urbano Teresa , Vinceti Marco , Wise Lauren A. , Filippini Tommaso
Published: October 2021

Breast cancer is the most common malignancy in women and the second leading cause of cancer death overall. Besides genetic, reproductive, and hormonal factors involved in disease onset and progression, greater attention has focused recently on the etiologic role of environmental factors, including exposure to artificial lighting such as light-at-night (LAN). We investigated the extent to which LAN, including outdoor and indoor exposure, affects breast cancer risk. We performed a systematic review of epidemiological evidence on the association between LAN exposure and breast cancer risk, using a dose–response meta-analysis to examine the shape of the relation. We retrieved 17 eligible studies through September 13, 2021, including ten cohort and seven case–control studies. In the analysis comparing highest versus lowest LAN exposure, we found a positive association between exposure and disease risk (risk ratio [RR] 1.11, 95% confidence interval-CI 1.07–1.15), with comparable associations in case–control studies (RR 1.14, 95% CI 0.98–1.34) and cohort studies (RR 1.10, 95% CI 1.06–1.15). In stratified analyses, risk was similar for outdoor and indoor LAN exposure, while slightly stronger risks were observed for premenopausal women (premenopausal: RR 1.16, 95% CI 1.04–1.28; postmenopausal: 1.07, 95% CI 1.02–1.13) and for women with estrogen receptor (ER) positive breast cancer (ER + : RR 1.09, 95% CI 1.02–1.17; ER–: RR 1.07, 95% CI 0.92–1.23). The dose–response meta-analysis, performed only in studies investigating outdoor LAN using comparable exposure assessment, showed a linear relation up to 40 nW/cm2/sr after which the curve flattened, especially among premenopausal women. This first assessment of the dose–response relation between LAN and breast cancer supports a positive association in selected subgroups, particularly in premenopausal women.
The prognostic value of intratumoral and peritumoral tumor-infiltrating FoxP3+Treg cells in of pancreatic adenocarcinoma: a meta-analysis
Authors: Hu Lingyu , Zhu Mingyuan , Shen Yiyu , Zhong Zhengxiang , Wu Bin
Published: October 2021

Background

Tumor-infiltrating lymphocytes (TILs) are major participants in the tumor microenvironment. The prognostic value of TILs in patients with pancreatic cancer is still controversial.

Methods

The aim of our meta-analysis was to determine the impact of FoxP3+Treg cells on the survival of pancreatic cancer patients. We searched for related studies in PubMed, EMBASE, Ovid, and Cochrane Library from the time the databases were established to Mar 30, 2017. We identified studies reporting the prognostic value of FoxP3+Treg cells in patients with pancreatic cancer. Overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS)/relapse-free survival (RFS) were investigated by pooling the data. The pooled hazard ratios (HRs) with 95% confidence intervals (95% CI) were used to evaluate the association between FoxP3+Treg cells and survival outcomes of pancreatic cancer patients. A total of 972 pancreatic cancer patients from 8 studies were included in our meta-analysis.

Results

High levels of infiltration with FoxP3+Treg cells were significantly associated with poor OS (HR=2.13; 95% CI 1.64–2.77; P<0.05) and poor DFS/PFS/RFS (HR=1.70; 95% CI 1.04 ~ 2.78; P< 0.05). Similar results were also observed in the peritumoral tissue; high levels of FoxP3+Treg cells were associated with poor OS (HR =2.1795% CI, CI 1.50–3.13).

Conclusion

This meta-analysis indicated that high levels of intratumoral or peritumoral FoxP3+Treg cell infiltration could be recognized as a negative factor in the prognosis of pancreatic cancer.
Impact of endometriosis on oocyte morphology in IVF-ICSI: retrospective study of a cohort of more than 6000 mature oocytes
Authors: Robin Camille , Uk Audrey , Decanter Christine , Behal Hélène , Collinet Pierre , Rubod Chrystèle , Barbotin Anne-Laure , Robin Geoffroy
Published: October 2021

Background

Infertility associated with endometriosis can be explained by several non-exclusive mechanisms. The oocyte plays a crucial role in determining embryonic competence and this is particularly relevant for in vitro fertilization (IVF) outcomes. According to some authors, the morphology of oocytes could also be a non-invasive marker of oocyte quality. The aim of this study was to evaluate the relationship between endometriosis and oocyte morphology after controlled ovarian stimulation for intracytoplasmic sperm injection (ICSI) on a large oocyte cohort.

Methods

Single-center comparative retrospective study in the academic In Vitro Fertilization (IVF) unit of the Lille University Hospital. A total of 596 women treated for IVF-ICSI with ejaculated spermatozoa for sperm alterations were included. They were classified as endometriosis (n = 175) or control groups (n = 401). The morphological evaluation of 2,016 mature oocytes from 348 cycles of patients with endometriosis was compared with that of 4,073 mature oocytes from 576 control cycles. The main outcome measures were Average Oocyte Quality Index (AOQI) and metaphase II oocyte morphological scoring system (MOMS). Comparison of groups was carried out by a mixed linear model and by a generalized estimation equation model with a "patient" random effect to consider that a patient might have several attempts.

Results

No difference in AOQI and MOMS scores was found between endometriosis and control women (adjusted p = 0.084 and 0.053, respectively).

In case of endometriosis, there were significantly fewer metaphase II oocytes retrieved, embryos obtained, grade 1 embryos and number of cumulative clinical pregnancies compared to controls. In the endometriosis group, endometriosis surgery was associated with a reduced number of mature oocytes retrieved, and the presence of endometrioma(s) was associated with some abnormal oocyte shapes. Nevertheless, no difference concerning the AOQI and MOMS scores was found in these subgroups.

Conclusion

Endometriosis does not have a negative impact on oocytes’ morphology in IVF-ICSI.

Trial registration

On December 16, 2019, the Institutional Review Board of the Lille University Hospital gave unrestricted approval for the anonymous use of all patients’ clinical, hormonal and ultrasound records (reference DEC20150715-0002).
Sodium phenylbutyrate inhibits Schwann cell inflammation via HDAC and NFκB to promote axonal regeneration and remyelination
Authors: Yadav Anjali , Huang Tzu-Chieh , Chen Szu-Han , Ramasamy Thamil Selvee , Hsueh Yuan-Yu , Lin Shau-Ping , Lu Fu-I , Liu Ya-Hsin , Wu Chia-Ching
Published: October 2021

Background

Epigenetic regulation by histone deacetylases (HDACs) in Schwann cells (SCs) after injury facilitates them to undergo de- and redifferentiation processes necessary to support various stages of nerve repair. Although de-differentiation activates the synthesis and secretion of inflammatory cytokines by SCs to initiate an immune response during nerve repair, changes in either the timing or duration of prolonged inflammation mediated by SCs can affect later processes associated with repair and regeneration. Limited studies have investigated the regulatory processes through which HDACs in SCs control inflammatory cytokines to provide a favorable environment for peripheral nerve regeneration.

Methods

We employed the HDAC inhibitor (HDACi) sodium phenylbutyrate (PBA) to address this question in an in vitro RT4 SC inflammation model and an in vivo sciatic nerve transection injury model to examine the effects of HDAC inhibition on the expression of pro-inflammatory cytokines. Furthermore, we assessed the outcomes of suppression of extended inflammation on the regenerative potential of nerves by assessing axonal regeneration, remyelination, and reinnervation.

Results

Significant reductions in lipopolysaccharide (LPS)-induced pro-inflammatory cytokine (tumor necrosis factor-α [TNFα]) expression and secretion were observed in vitro following PBA treatment. PBA treatment also affected the transient changes in nuclear factor κB (NFκB)-p65 phosphorylation and translocation in response to LPS induction in RT4 SCs. Similarly, PBA mediated long-term suppressive effects on HDAC3 expression and activity. PBA administration resulted in marked inhibition of pro-inflammatory cytokine secretion at the site of transection injury when compared with that in the hydrogel control group at 6-week post-injury. A conducive microenvironment for axonal regrowth and remyelination was generated by increasing expression levels of protein gene product 9.5 (PGP9.5) and myelin basic protein (MBP) in regenerating nerve tissues. PBA administration increased the relative gastrocnemius muscle weight percentage and maintained the intactness of muscle bundles when compared with those in the hydrogel control group.

Conclusions

Suppressing the lengthened state of inflammation using PBA treatment favors axonal regrowth and remyelination following nerve transection injury. PBA treatment also regulates pro-inflammatory cytokine expression by inhibiting the transcriptional activation of NFκB-p65 and HDAC3 in SCs in vitro.
A novel phosphoproteomic landscape evoked in response to type I interferon in the brain and in glial cells
Authors: Viengkhou Barney , White Melanie Y. , Cordwell Stuart J. , Campbell Iain L. , Hofer Markus J.
Published: October 2021

Background

Type I interferons (IFN-I) are key responders to central nervous system infection and injury and are also increased in common neurodegenerative diseases. Their effects are primarily mediated via transcriptional regulation of several hundred interferon-regulated genes. In addition, IFN-I activate several kinases including members of the MAPK and PI3K families. Yet, how changes to the global protein phosphoproteome contribute to the cellular response to IFN-I is unknown.

Methods

The cerebral phosphoproteome of mice with brain-targeted chronic production of the IFN-I, IFN-α, was obtained. Changes in phosphorylation were analyzed by ontology and pathway analysis and kinase enrichment predictions. These were verified by phenotypic analysis, immunohistochemistry and immunoblots. In addition, primary murine microglia and astrocytes, the brain's primary IFN-I-responding cells, were acutely treated with IFN-α and the global phosphoproteome was similarly analyzed.

Results

We identified widespread protein phosphorylation as a novel mechanism by which IFN-I mediate their effects. In our mouse model for IFN-I-induced neurodegeneration, protein phosphorylation, rather than the proteome, aligned with the clinical hallmarks and pathological outcome, including impaired development, motor dysfunction and seizures. In vitro experiments revealed extensive and rapid IFN-I-induced protein phosphorylation in microglia and astrocytes. Response to acute IFN-I stimulation was independent of gene expression and mediated by a small number of kinase families. The changes in the phosphoproteome affected a diverse range of cellular processes and functional analysis suggested that this response induced an immediate reactive state and prepared cells for subsequent transcriptional responses.

Conclusions

Our studies reveal a hitherto unappreciated role for changes in the protein phosphorylation landscape in cellular responses to IFN-I and thus provide insights for novel diagnostic and therapeutic strategies for neurological diseases caused by IFN-I.
Tocilizumab in HIV patient with severe COVID-19: case report
Authors: Bertozzi Pedro Vieira , de Oliveira Vicente Amanda , Pereira Amanda Siqueira , de Sant’Ana Joao Pedro Espinha , Mano Rafaela Braga Cabrera , Jorge Luciana Souza , da Silva Sardenberg Rodrigo Afonso
Published: October 2021

Background

A 73-year-old male patient who had a history of Human Immunodeficiency Virus (HIV) infection for over 20 years was diagnosed with SARS-CoV-2 infection.

Case presentation

The patient was admitted to the Intensive Care Unit (ICU), where he remained for 25 days, due to a severe condition. Intubation, hemodialysis, and tracheostomy were necessary to maintain homeostasis. In addition to regular treatment with etravirine, dolutegravir, darunavir, and ritonavir for highly active antiretroviral therapy, the patient received tocilizumab, which showed a great recovery in the patient’s condition.

Conclusion

The patient had several risk factors, such as male gender, age  >  70 years, and arterial hypertension. The use of tocilizumab was of great importance in the patient’s recovery since the drug increased his immune response, which is deficient, due to HIV infection.
The anti-diabetic effects of betanin in streptozotocin-induced diabetic rats through modulating AMPK/SIRT1/NF-κB signaling pathway
Authors: Abedimanesh Nasim , Asghari Somayyeh , Mohammadnejad Kosar , Daneshvar Zahra , Rahmani Soudeh , Shokoohi Samaneh , Farzaneh Amir Hasan , Hosseini Seyed Hojjat , Jafari Anarkooli Iraj , Noubarani Maryam , Andalib Sina , Eskandari Mohammad Reza , Motlagh Behrooz
Published: October 2021

Background

In the last few years, the effects of bioactive food components have received much attention because of their beneficial effects including decreasing inflammation, scavenging free radicals, and regulating cell signaling pathways. Betanin as a potent antioxidant has been previously reported to exhibit anti diabetic effects. The present study aimed to evaluate the effects of betanin on glycemic control, lipid profile, hepatic function tests, as well as the gene expression levels of 5′ adenosine monophosphate‑activated protein kinase (AMPK), sirtuin-1 (SIRT1), and nuclear factor kappa B (NF‑κB) in streptozocin (STZ) induced diabetic rats.

Methods

Diabetes was induced in male Sprague–Dawley rats by intraperitoneal administration of STZ. Different doses of betanin (10, 20 and 40 mg/kg.b.w) was administered to diabetic rats for 28 days. Fasting blood glucose and serum insulin were measured. The histopathology of liver and pancreas tissue evaluated. Real-time PCR was performed to assess gene expression levels.

Results

Treatment of diabetic rats with betanin (10 and 20 mg/kg.b.w) reduced FBG levels compared to the control diabetic rats (P < 0.001). Betanin at the dose of 20 mg/kg.b.w was most effective in increasing serum insulin levels (P < 0.001) improving glucose tolerance test (GTT) as well as improvement in lipid profile and liver enzymes levels. According to histopathologic assay, different damages induced by STZ to liver and pancreas tissues was largely eliminated by treatment with 10 and 20 mg/kg.b.w of betanin. Betanin also significantly upregulated the AMPK and SIRT1 and downregulated the NF-κB mRNA expression compared to the diabetic control rats (P < 0.05).

Conclusion

Betanin could modulate AMPK/SIRT1/NF-κB signaling pathway and this may be one of its anti-diabetic molecular mechanisms.
Selection of medicinal plants for traditional medicines in Nepal
Authors: Kutal Durga H. , Kunwar Ripu M. , Uprety Yadav , Adhikari Yagya P. , Bhattarai Shandesh , Adhikari Binaya , Kunwar Laxmi M. , Bhatt Man D. , Bussmann Rainer W.
Published: October 2021

Background

There are handful hypothesis-driven ethnobotanical studies in Nepal. In this study, we tested the non-random medicinal plant selection hypothesis using national- and community-level datasets through three different types of regression: linear model with raw data, linear model with log-transformed data and negative binomial model.

Methods

For each of these model, we identified over-utilized families as those with highest positive Studentized residuals and underutilized families with highest negative Studentized residuals. The national-level data were collected from online databases and available literature while the community-level data were collected from Baitadi and Darchula districts.

Results

Both dataset showed larger variance (national dataset mean 6.51 < variance 156.31, community dataset mean 1.16 < variance 2.38). All three types of regression were important to determine the medicinal plant species selection and use differences among the total plant families, although negative binomial regression was most useful. The negative binomial showed a positive nonlinear relationship between total plant family size and number of medicinal species per family for the national dataset (β1 = 0.0160 ± 0.0009,Z1 = 16.59,p < 0.00001, AIC1 = 1181), and with similar slope and stronger performance for the community dataset (β2 = 0.1747 ± 0.0199,Z2 = 8.76,p < 0.00001, AIC2 = 270.78). Moraceae and Euphorbiaceae were found over-utilized while Rosaceae, Cyperaceae and Caryophyllaceae were recorded as underutilized.

Conclusions

As our datasets showed larger variance, negative binomial regression was found the most useful for testing non-random medicinal plant selection hypothesis. The predictions made by non-random selection of medicinal plants hypothesis holds true for community-level studies. The identification of over-utilized families is the first step toward sustainable conservation of plant resources and it provides a baseline for pharmacological research that might be leading to drug discovery.
Combined therapy of platelet-rich plasma and basic fibroblast growth factor using gelatin-hydrogel sheet for rotator cuff healing in rat models
Authors: Kataoka Takeshi , Mifune Yutaka , Inui Atsuyuki , Nishimoto Hanako , Kurosawa Takashi , Yamaura Kohei , Mukohara Shintaro , Matsushita Takehiko , Niikura Takahiro , Tabata Yasuhiko , Kuroda Ryosuke
Published: October 2021

Introduction

Excellent outcomes of arthroscopic rotator cuff repair for small and medium tears have been recently reported. However, re-tears after surgery have been a common complication after surgical repair of large and massive rotator cuff tears and often occur in early postoperative phase. It was previously reported that basic fibroblast growth factor and platelet-rich plasma enhanced rotator cuff tear healing. We hypothesized that this combined therapy could enhance rotator cuff healing after rotator cuff repair in a rat model. This study aimed to evaluate the efficacy of combined therapy of platelet-rich plasma and basic fibroblast growth factor with gelatin-hydrogel sheet.

Methods

To create a rotator cuff defect, the infraspinatus tendon of Sprague Dawley rat was resected from the greater tuberosity. The infraspinatus tendons were repaired and covered with gelatin-hydrogel sheet impregnated with PBS (control group), basic fibroblast growth factor (bFGF group), platelet-rich plasma (PRP group), or both basic fibroblast growth factor and platelet-rich plasma (combined group). Histological examinations were conducted using hematoxylin and eosin, safranin O, and immunofluorescence staining, such as Isolectin B4, type II collagen at 2 weeks postoperatively. For mechanical analysis, ultimate failure load of the tendon-humeral head complex was evaluated at 6 weeks postoperatively.

Results

In the hematoxylin and eosin staining, the tendon maturing score of the combined group was higher than that of the control group at postoperative 2 weeks. In the safranin O staining, stronger proteoglycan staining was observed in the combined group compared with the other groups at postoperative 2 weeks. Vascular staining with isolectin B4 in 3 treatment groups was significantly higher than that in the control group. Type II collagen expression in the combined group was significantly higher than those in the other groups. The ultimate failure load of the combined group was significantly higher than that of the control group.

Conclusion

Combined therapy of basic fibroblast growth factor and platelet-rich plasma promoted angiogenesis, tendon maturing and fibrocartilage regeneration at the enthesis, which could enhance the mechanical strength. It was suggested that combined basic fibroblast growth factor and platelet-rich plasma might enhance both tendon and bone–tendon junction healing, and basic fibroblast growth factor and platelet-rich plasma might be synergistic.
A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot–Marie–Tooth type 1A
Authors: Attarian Shahram , Young Peter , Brannagan Thomas H. , Adams David , Van Damme Philip , Thomas Florian P. , Casanovas Carlos , Kafaie Jafar , Tard Céline , Walter Maggie C. , Péréon Yann , Walk David , Stino Amro , de Visser Marianne , Verhamme Camiel , Amato Anthony , Carter Gregory , Magy Laurent , Statland Jeffrey M. , Felice Kevin
Published: October 2021

Background

Charcot–Marie–Tooth disease type 1A (CMT1A) is a rare, orphan, hereditary neuromuscular disorder with no cure and for which only symptomatic treatment is currently available. A previous phase 2 trial has shown preliminary evidence of efficacy for PXT3003 in treating CMT1A. This phase 3, international, randomized, double-blind, placebo-controlled study further investigated the efficacy and safety of high- or low-dose PXT3003 (baclofen/naltrexone/D-sorbitol [mg]: 6/0.70/210 or 3/0.35/105) in treating subjects with mild to moderate CMT1A.

Methods

In this study, 323 subjects with mild-to-moderate CMT1A were randomly assigned in a 1:1:1 ratio to receive 5 mL of high- or low-dose PXT3003, or placebo, orally twice daily for up to 15 months. Efficacy was assessed using the change in Overall Neuropathy Limitations Scale total score from baseline to months 12 and 15 (primary endpoint). Secondary endpoints included the 10-m walk test and other assessments. The high-dose group was discontinued early due to unexpected crystal formation in the high-dose formulation, which resulted in an unanticipated high discontinuation rate, overall and especially in the high-dose group. The statistical analysis plan was adapted to account for the large amount of missing data before database lock, and a modified full analysis set was used in the main analyses. Two sensitivity analyses were performed to check the interpretation based on the use of the modified full analysis set.

Results

High-dose PXT3003 demonstrated significant improvement in the Overall Neuropathy Limitations Scale total score vs placebo (mean difference: − 0.37 points; 97.5% CI [− 0.68 to − 0.06]; p = 0.008), and consistent treatment effects were shown in the sensitivity analyses. Both PXT3003 doses were safe and well-tolerated.

Conclusion

The high-dose group demonstrated a statistically significant improvement in the primary endpoint and a good safety profile. Overall, high-dose PXT3003 is a promising treatment option for patients with Charcot–Marie–Tooth disease type 1A.
The role of the tumor microbe microenvironment in the tumor immune microenvironment: bystander, activator, or inhibitor?
Authors: Ma Jiayao , Huang Lingjuan , Hu Die , Zeng Shan , Han Ying , Shen Hong
Published: October 2021

The efficacy of cancer immunotherapy largely depends on the tumor microenvironment, especially the tumor immune microenvironment. Emerging studies have claimed that microbes reside within tumor cells and immune cells, suggesting that these microbes can impact the state of the tumor immune microenvironment. For the first time, this review delineates the landscape of intra-tumoral microbes and their products, herein defined as the tumor microbe microenvironment. The role of the tumor microbe microenvironment in the tumor immune microenvironment is multifaceted: either as an immune activator, inhibitor, or bystander. The underlying mechanisms include: (I) the presentation of microbial antigens by cancer cells and immune cells, (II) microbial antigens mimicry shared with tumor antigens, (III) microbe-induced immunogenic cell death, (IV) microbial adjuvanticity mediated by pattern recognition receptors, (V) microbe-derived metabolites, and (VI) microbial stimulation of inhibitory checkpoints. The review further suggests the use of potential modulation strategies of the tumor microbe microenvironment to enhance the efficacy and reduce the adverse effects of checkpoint inhibitors. Lastly, the review highlights some critical questions awaiting to be answered in this field and provides possible solutions. Overall, the tumor microbe microenvironment modulates the tumor immune microenvironment, making it a potential target for improving immunotherapy. It is a novel field facing major challenges and deserves further exploration.
Serological assessment of collagen fragments and tumor fibrosis may guide immune checkpoint inhibitor therapy
Authors: Jensen Christina , Nissen Neel I. , Von Arenstorff Claus S. , Karsdal Morten A. , Willumsen Nicholas
Published: October 2021

Despite the overall clinical success of immune checkpoint inhibitors (ICIs) for treating patients with solid tumors, a large number of patients do not benefit from this approach. Consequently, there is a need for predictive biomarkers. The most prevalent biomarkers such as PD-L1 expression and tumor mutational burden (TMB) do not reliably predict response to ICIs across different solid tumor types suggesting that a broader view of regulating factors in the tumor microenvironment is needed. Emerging evidence indicates that one central common denominator of resistance to ICIs may be fibrotic activity characterized by extracellular matrix (ECM) and collagen production by cancer-associated fibroblasts (CAFs). A fibroblast-and collagen-rich stroma attenuates immunotherapy response by contributing to inhibition and exclusion of T cells. Here we review opportunities and limitations in the utilization of the most prevalent biomarkers for ICIs and elaborate on the unique opportunities with biomarkers originating from the activated fibroblasts producing an impermeable ECM. We propose that ECM and collagen biomarkers measured non-invasively may be a novel and practical approach to optimize treatment strategies and improve patient selection for ICI therapy.
Pre-hospital suPAR, lactate and CRP measurements for decision-making: a prospective, observational study of patients presenting non-specific complaints
Authors: Jousi Milla , Mäkinen Marja , Kaartinen Johanna , Meriläinen Leena , Castrén Maaret
Published: October 2021

Background

In the pre-hospital setting, non-urgent patients with non-specific chief complaints pose assessment challenges for the emergency medical systems (EMS). Severely ill patients should be identified among these patients, and unnecessary transport to the emergency department (ED) should be avoided. Unnecessary admissions burden EDs, deplete EMS resources and can even be harmful to patients, especially elderly patients. Therefore, tools for facilitating pre-hospital decision-making are needed. They could be based on vital signs or point-of-care laboratory biomarkers. In this study, we examined whether the biomarker soluble urokinase plasminogen activator receptor (suPAR), either alone or combined with C-reactive protein (CRP) and/or lactate, could predict discharge from the ED and act as a pre-hospital support tool for non-conveyance decision-making.

Methods

This was a prospective, observational study of adult patients with normal or near-normal vital signs transported by an EMS to an ED with a code referring to deteriorated general condition. The levels of suPAR, CRP and lactate in the patients’ pre-hospital blood samples were analysed. The values of hospitalized patients were compared to those of discharged patients to determine whether these biomarkers could predict direct discharge from the ED.

Results

A total of 109 patients (median age: 81 years) were included in the study. Of those, 52% were hospitalized and 48% were discharged from the ED. No statistically significant association was found between suPAR and the ED discharge vs hospitalization outcome (OR: 1.04, 95% CI 0.97–1.13, AUROC: 0.58, 95% CI 0.47–0.69). Adding CRP (AUROC: 0.64, 95% CI 0.54–0.75) or lactate (AUROC: 0.60, 95% CI 0.49–0.71) to the regression models did not improve their diagnostic accuracy. None of the patients with a suPAR value of less than 2 ng/ml were admitted to hospital, while 64% of the patients with a suPAR value of more than 6 ng/ml were hospitalized.

Conclusion

Pre-hospital suPAR measurements alone or combined with CRP and/or lactate measurements could not predict the ED discharge or hospital admission of 109 non-urgent EMS patients with non-specific chief complaints and normal or near-normal vital signs.
The development of emergency medical services benefit score: a European Delphi study
Authors: Heino Anssi , Raatiniemi Lasse , Iirola Timo , Meriläinen Merja , Liisanantti Janne , Tommila Miretta ,   Collaboration Group, Krüger Andreas , Dami Fabrice , Moens Didier , Fevang Espen , Harve-Rytsälä Heini , Jäntti Helena , Nurmi Jouni , Tønsager Kristin , Rognås Leif , Rehn Marius , Schober Patrick , Bredmose Per P. , Hansen Peter Martin , Temesvari Peter , Mikkelsen Søren , Lindner Thomas W. , Hansen Troels Martin , Nikula Anna , Kantanen Anne-Mari , Lindgren Antti E. , Salmi Heli , Kirjasuo Karri , Varpula Marjut , Reinikainen Matti , Paalasmaa Nanneli , Peltoniemi Outi , Luoto Teemu , Lund Vesa , Jalkanen Ville
Published: October 2021

Background

The helicopter emergency services (HEMS) Benefit Score (HBS) is a nine-level scoring system developed to evaluate the benefits of HEMS missions. The HBS has been in clinical use for two decades in its original form. Advances in prehospital care, however, have produced demand for a revision of the HBS. Therefore, we developed the emergency medical services (EMS) Benefit Score (EBS) based on the former HBS. As reflected by its name, the aim of the EBS is to measure the benefits produced by the whole EMS systems to patients.

Methods

This is a four-round, web-based, international Delphi consensus study with a consensus definition made by experts from seven countries. Participants reviewed items of the revised HBS on a 5-point Likert scale. A content validity index (CVI) was calculated, and agreement was defined as a 70% CVI. Study included experts from seven European countries. Of these, 18 were prehospital expert panellists and 11 were in-hospital commentary board members.

Results

The first Delphi round resulted in 1248 intervention examples divided into ten diagnostic categories. After removing overlapping examples, 413 interventions were included in the second Delphi round, which resulted in 38 examples divided into HBS categories 3–8. In the third Delphi round, these resulted in 37 prehospital interventions, examples of which were given revised version of the score. In the fourth and final Delphi round, the expert panel was given an opportunity to accept or comment on the revised scoring system.

Conclusions

The former HBS was revised by a Delphi methodology and EBS developed to represent its structural purpose better. The EBS includes 37 exemplar prehospital interventions to guide its clinical use.

Trial registration The study permission was requested and granted by Turku University Hospital (decision number TP2/010/18).