bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse childhood experiences and comorbidity in a cohort of people who have injected drugs
Authors: Sosnowski David W. , Feder Kenneth A. , Astemborski Jacquie , Genberg Becky L. , Letourneau Elizabeth J. , Musci Rashelle J. , Mojtabai Ramin , McCall Lisa , Hollander Eileen , Loving Lynnet , Maher Brion S. , Kirk Gregory D. , Mehta Shruti H. , Sun Jing
Published: May 2022

Background

Childhood adversity is associated with the onset of harmful adult substance use and related health problems, but most research on adversity has been conducted in general population samples. This study describes the prevalence of adverse childhood experiences in a cohort of people who have injected drugs and examines the association of these adverse experiences with medical comorbidities in adulthood.

Methods

Six hundred fifty three adults were recruited from a 30-year cohort study on the health of people who have injected drugs living in and around Baltimore, Maryland (Median age = 47.5, Interquartile Range = 42.3–52.3 years; 67.3% male, 81.1% Black). Adverse childhood experiences were assessed retrospectively in 2018 via self-report interview. Lifetime medical comorbidities were ascertained via self-report of a provider diagnosis. Multinomial logistic regression with generalized estimating equations was used to examine the association between adversity and comorbid conditions, controlling for potential confounders.

Results

Two hundred twelve participants (32.9%) reported 0–1 adverse childhood experiences, 215 (33.3%) reported 2–4, 145 (22.5%) reported 5–9, and 72 (11.1%) reported ≥10. Neighborhood violence was the most commonly reported adversity (48.5%). Individuals with ≥10 adverse childhood experiences had higher odds for reporting ≥3 comorbidities (Adjusted Odds Ratio = 2.9, 95% CI = 1.2 – 6.8, p = .01).

Conclusions

Among people who have injected drugs, adverse childhood experiences were common and associated with increased occurrence of self-reported medical comorbidities. Findings highlight the persistent importance of adversity for physical health even in a population where all members have used drugs and there is a high burden of comorbidity.
Dietary and lifestyle indices for hyperinsulinemia with the risk of obesity phenotypes: a prospective cohort study among Iranian adult population
Authors: Teymoori Farshad , Mokhtari Ebrahim , Kazemi Jahromi Mitra , Farhadnejad Hossein , Mirmiran Parvin , Vafa Mohammadreza , Azizi Fereidoun
Published: May 2022

Background

Previous studies have cited insulin-related disorders, including hyperinsulinemia, as one of the main causes of obesity risk and metabolic disorders. We aimed to investigate the association of the Empirical Dietary Index for Hyperinsulinemia (EDIH) and Empirical Lifestyle Index for Hyperinsulinemia (ELIH) with the risk of obesity phenotypes among Iranian adults.

Methods

Present study was conducted on 2705 subjects, including 1604 metabolically healthy normal weights (MHNW) and 1101 metabolically healthy obesity (MHO) individuals. Obesity phenotypes, including MHNW, MHO, metabolically unhealthy normal weights (MUNW), and metabolic unhealthy obesity (MUO), were determined using the criteria of the Joint International statement (JIS) for metabolic syndrome. Dietary intake data from the previous year was gathered using a food frequency questionnaire. Cox proportional hazard regression was used to estimate the hazard ratio and 95% confidence intervals (HRs and 95% CIs) of obesity phenotypes incident across tertiles of EDIH and ELIH scores.

Results

The mean ± SD of age and BMI of all participants were 33.5 ± 12.2 years and 24.3 ± 3.8 kg/m2, respectively. In the multivariable-adjusted model, a higher ELIH score was associated with a greater risk for incidence of MUO (HR: 3.47, 95%CI: 2.54–4.74; Ptrend =  < 0.001) and MHO (HR: 3.61, 95%CI: 2.73–4.77; Ptrend =  < 0.001). Also, a higher score of EDIH was related to an increased risk of MUO incidence (HR: 1.35, 95%CI: 1.02–1.79; P for trend = 0.046). However, there was no significant association between a higher score of EDIH and the risk of MHO.

Conclusion

Our findings revealed that a high insulinemic potential of diet and lifestyle, determined by EDIH and ELIH indices, may be related to an increase in the simultaneous occurrence of obesity with metabolic disorders in Iranian adults.
Comparison of pulmonary function test, diffusion capacity, blood gas analysis and CT scan in patients with and without persistent respiratory symptoms following COVID-19
Authors: Lehmann Antje , Gysan Maximilian , Bernitzky Dominik , Bal Christina , Prosch Helmut , Zehetmayer Sonja , Milos Ruxandra-Iulia , Vonbank Karin , Pohl Wolfgang , Idzko Marco , Gompelmann Daniela
Published: May 2022

Background

Long-lasting symptoms following SARS-CoV2-infection have been described in several studies. However, there is only limited knowledge about the ongoing pathophysiology and the association with pathological findings in medical examinations.

Methods

In this post hoc analysis of a prospective trial, 135 patients following COVID-19 were enrolled and grouped with respect to the presence or absence of respiratory ongoing symptoms following COVID-19. Pulmonary function test (PFT), diffusion capacity measurement (TLCO SB and TLCO/VA), blood gas analysis (BGA), laboratory tests and high-resolution computed tomography (HRCT) of patients with persistent respiratory symptoms were compared to those of asymptomatic patients.

Results

In this analysis, 71% (96/135) of all patients (mean age 49 years; range 20–91 years) reported long-lasting symptoms after a median (IQR) of 85 days (60–116) following COVID-19 whereby 57.8% (78/135) complained about persistent pulmonary symptoms. Pathological findings in blood test, PFT, TLCO, BGA and/or HRCT were found in 71.8% and 64.1% of patients with and without long-lasting respiratory symptoms respectively. Patients with persistent respiratory symptoms were significantly younger and presented a significant lower FVC (%), TLC (L), and TLCO SB compared to asymptomatic patients (p < 0.05). The multiple logistic regression results in a significant effect of age (p = 0.004) and TLCO SB (p = 0.042).

Conclusion

Following COVID-19, a large proportion of patients experience ongoing symptoms, whereby the respiratory symptoms are the predominant complaints. Compared to asymptomatic patients, patients with ongoing symptoms were younger and presented a significant lower FVC, TLC and TLCO SB. The multiple logistic regression demonstrated only a significant association between the TLCO SB as the only PFT parameter and the perceived symptoms.
Cytotoxic activity of non-specific lipid transfer protein (nsLTP1) from Ajwain (Trachyspermum ammi) seeds
Authors: Alshammari Saud O. , Aldakhil Taibah , Alshammari Qamar A. , Salehi David , Ahmed Aftab
Published: May 2022

Background

Trachyspermum ammi, commonly known as Ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered.

Aim

The current study aimed to demonstrate the cytotoxic activity of Ajwain non-specific lipid transfer protein (nsLTP1) in normal breast (MCF10A), breast cancer (MCF-7), and pancreatic cancer (AsPC-1) cell lines. Also, to evaluate its structural stability in human serum as well as at high temperature conditions.

Methods

The cytotoxic activity of Ajwain nsLTP1 was evaluated in MCF-7 and AsPC-1 cell lines using MTT assay. Annexin V-FITC and PI staining were used to detect the early apoptotic and late apoptotic cells. The role of nsLTP1 in inducing apoptosis was further studied by quantifying Bcl-2, Bax, Caspase-3, Survivin, EGFR, and VEGF genes expression using RT-PCR. CD spectroscopy analyzed the nsLTP1 conformational changes after thermal treatment for structure stability determination. The RP-HPLC was used to analyze the nsLTP1 degradation rate in human serum at different time intervals incubated at 37 °C.

Results

Ajwain nsLTP1 showed a potent cytotoxic effect in MCF-7 and AsPC-1. The IC50 value obtained in MCF-7 was 8.21 μM, while for AsPC-1 4.17 μM. The effect of nsLTP1 on stimulating apoptosis revealed that the proportions of apoptotic cells in both cell lines were relatively increased depending on the concentration. The apoptotic cells percentage at 20 μM was in MCF-7 71% (***P < 0.001) and AsPC-1 88% (***P < 0.001). These results indicate that nsLTP1 might efficaciously induce apoptosis in multiple types of cancerous cells. Genes expression in MCF-7 and AsPC-1 showed significant upregulation in Bax and Caspase-3 and downregulation in Bcl-2, Survivin, EGFR, and VEGF protein. The CD analysis of nsLTP1 showed a significant thermostable property. In serum, nsLTP1 showed a slow degradation rate, indicating high stability with a half-life of ~ 8.4 h.

Conclusion

Our results revealed the potential anticancer activity of Ajwain nsLTP1 and its mechanism in inducing apoptosis. It further exhibited thermostable properties at high temperatures and in human serum, which suggested this protein as a promising anticancer agent.
The impact of small-group virtual patient simulator training on perceptions of individual learning process and curricular integration: a multicentre cohort study of nursing and medical students
Authors: Mestre André , Muster Marek , El Adib Ahmed Rhassane , Ösp Egilsdottir Hugrun , Byermoen Kirsten Røland , Padilha Miguel , Aguilar Thania , Tabagari Nino , Betts Lorraine , Sales Leila , Garcia Pedro , Ling Luo , Café Hugo , Binnie Alexandra , Marreiros Ana
Published: May 2022

Background

The COVID-19 pandemic has precipitated rapid changes in medical education to protect students and patients from the risk of infection. Virtual Patient Simulators (VPS) provide a simulated clinical environment in which students can interview and examine a patient, order tests and exams, prioritize interventions, and observe response to therapy, all with minimal risk to themselves and their patients. Like high-fidelity simulators (HFS), VPS are a tool to improve curricular integration. Unlike HFS, VPS require limited infrastructure investment and can be used in low-resource settings. Few studies have examined the impact of VPS training on clinical education. This international, multicenter cohort study was designed to assess the impact of small-group VPS training on individual learning process and curricular integration from the perspective of nursing and medical students.

Methods

We conducted a multi-centre, international cohort study of nursing and medical students. Baseline perceptions of individual learning process and curricular integration were assessed using a 27-item pre-session questionnaire. Students subsequently participated in small-group VPS training sessions lead by a clinical tutor and then completed a 32-item post-session questionnaire, including 25 paired items. Pre- and post-session responses were compared to determine the impact of the small-group VPS experience.

Results

Participants included 617 nursing and medical students from 11 institutions in 8 countries. At baseline, nursing students reported greater curricular integration and more clinical and simulation experience than did medical students. After exposure to small-group VPS training, participants reported significant improvements in 5/6 items relating to individual learning process and 7/7 items relating to curricular integration. The impact of the VPS experience was similar amongst nursing and medical students.

Conclusions

In this multi-centre study, perceptions of individual learning process and curricular integration improved after exposure to small-group VPS training. Nursing and medical students showed similar impact. Small-group VPS training is an accessible, low-risk educational strategy that can improve student perceptions of individual learning process and curricular integration.
Decision-making approaches for children with life-limiting conditions: results from a qualitative phenomenological study
Authors: Vemuri Sidharth , Hynson Jenny , Williams Katrina , Gillam Lynn
Published: May 2022

Background

For children with life-limiting conditions who are unable to participate in decision-making, decisions are made for them by their parents and paediatricians. Shared decision-making is widely recommended in paediatric clinical care, with parents preferring a collaborative approach in the care of their child. Despite the increasing emphasis to adopt this approach, little is known about the roles and responsibilities taken by parents and paediatricians in this process. In this study, we describe how paediatricians approach decision-making for a child with a life-limiting condition who is unable to participate in decision-making for his/herself.

Methods

This qualitative phenomenological study involved 25 purposively sampled paediatricians. Verbatim transcripts from individual semi-structured interviews, conducted between mid-2019 and mid-2020, underwent thematic analysis. Interviews were based around a case vignette matched to the clinical experience of each paediatrician.

Results

Two key themes were identified in the exploration of paediatricians' approach to decision-making for children with life-limiting conditions: (1) there is a spectrum of paediatricians’ roles and responsibilities in decision-making, and (2) the specific influences on paediatricians’ choice of approach for end-of-life decisions. In relation to (1), analysis showed four distinct approaches: (i) non-directed, (ii) joint, (iii) interpretative, and (iv) directed. In relation to (2), the common factors were: (i) harm to the child, (ii) possible psychological harm to parents, (iii) parental preferences in decision-making, and (iv) resource allocation.

Conclusions

Despite self-reporting shared decision-making practices, what paediatricians often described were physician-led decision-making approaches. Adopting these approaches was predominantly justified by paediatricians’ considerations of harm to the child and parents. Further research is needed to elucidate the issues identified in this study, particularly the communication within and parental responses to physician-led approaches. We also need to further study how parental needs are identified in family-led decision-making approaches. These nuances and complexities are needed for future practice guidance and training around paediatric decision-making.

Trial registration:Not applicable.
Predicting acute kidney injury following open partial nephrectomy treatment using SAT-pruned explainable machine learning model
Authors: Lazebnik Teddy , Bahouth Zaher , Bunimovich-Mendrazitsky Svetlana , Halachmi Sarel
Published: May 2022

Background

One of the most prevalent complications of Partial Nephrectomy (PN) is Acute Kidney Injury (AKI), which could have a negative impact on subsequent renal function and occurs in up to 24.3% of patients undergoing PN. The aim of this study was to predict the occurrence of AKI following PN using preoperative parameters by applying machine learning algorithms.

Methods

We included all adult patients (n = 723) who underwent open PN in our department since 1995 and on whom we have data on the pre-operative renal function. We developed a random forest (RF) model with Boolean satisfaction-based pruned decision trees for binary classification (AKI or non-AKI). Hyper-parameter grid search was performed to optimize the model's performance. Fivefold cross-validation was applied to evaluate the model. We implemented a RF model with greedy feature selection to binary classify AKI and non-AKI cases based on pre-operative data.

Results

The best model obtained a 0.69 precision and 0.69 recall in classifying the AKI and non-AKI groups on average (k = 5). In addition, the model's probability to correctly classify a new prediction is 0.75. The proposed model is available as an online calculator.

Conclusions

Our model predicts the occurrence of AKI following open PN with (75%) accuracy. We plan to externally validate this model and modify it to minimally-invasive PN.
Nurses’ knowledge and understanding of obstacles encountered them when administering resuscitation medications: a cross-sectional study from Palestine
Authors: Qedan Rawan I. , Daibes Marah A. , Al-Jabi Samah W. , Koni Amer A. , Zyoud Sa’ed H.
Published: May 2022

Background

Medication errors (ME) are one of the most important reasons for patient morbidity and mortality, but insufficient drug knowledge among nurses is considered a major factor in drug administration errors. Furthermore, the complex and stressful systems surrounding resuscitation events increase nursing errors.

Aims

This study aimed to assess the knowledge about resuscitation medications and understand the obstacles faced by nurses when giving resuscitation medications. Additionally, errors in the reporting of resuscitation medication administration and the reasons that prevented nurses from reporting errors were investigated.

Methods

A cross-sectional study was conducted in the West Bank, Palestine. Convenient sampling was used to collect data, which was collected via a face-to-face interview questionnaire taken from a previous study. The questionnaire consisted of five parts: demographic data, knowledge of resuscitation medications (20 true/false questions), self-evaluation and causes behind not reporting ME, with suggestions to decrease ME.

Results

A total of 200 nurses participated in the study. Nurses were found to have insufficient knowledge about resuscitation medications (58.6%). A high knowledge score was associated with male nurses, those working in the general ward, the cardiac care unit (CCU), the intensive care unit (ICU) and the general ward. The main obstacles nurses faced when administering resuscitation medication were the chaotic environment in cardiopulmonary resuscitation (62%), the unavailability of pharmacists for a whole day (61%), and different medications that look alike in the packaging (61%). Most nurses (70.5%) hoped to gain additional training. In our study, we found no compatibility in the definition of ME between nurses and hospitals (43.5%).

Conclusions

Nurses had insufficient knowledge of resuscitation medications. One of the obstacles nurses faced was that pharmacists should appropriately arrange medications, and nurses wanted continuous learning and additional training about resuscitation medications to decrease ME.
Use of simulation to improve nursing students’ medication administration competence: a mixed-method study
Authors: Pol-Castañeda Sandra , Carrero-Planells Alba , Moreno-Mulet Cristina
Published: May 2022

Background

Medication administration errors are among the most important adverse events in healthcare systems. To minimise the risk of this occurring, nursing training programmes should emphasise the overriding priority of patient safety. In this respect, simulation can be a valuable resource in teaching procedures, for patient safety in general and safe medication administration in particular. In this study, we evaluate the use of a simulation-based activity for students to acquire skills in safe medication administration, and consider the students’ perceptions of this activity.

Methods

Second-year nursing students enrolled in the subject of pharmacology at a Spanish university during the academic year 2018–2019 were invited to participate in this mixed-method study. Their acquisition of professional competencies via a simulation exercise was evaluated according to the ‘six rights’. Before the simulation, each student completed a researcher-developed online questionnaire. The simulation was evaluated by the students’ tutor, using a checklist. A descriptive analysis was made of the data obtained from the questionnaire and during the simulation. At the end of the semester, the students' opinions were recorded in the questionnaire, in response to an open question. A content analysis was made of the responses to the open question.

Results

The simulation exercise was performed by 179 students, of whom 73 had previously completed the questionnaire. Analysis showed that, in comparison with the pre-simulation questionnaire results, compliance with the six rights improved in all dimensions except data documentation: right patient (from 64.4% to 83.3%); right medication (from 60.3% to 95.8%); right dose (from 60.3% to 100%); right route (from 54.8% to 95.8%); right time (from 24.7% to 70.8%); the right documentation result fell from 54.8% to 45.8%. The students expressed their satisfaction with the simulation method, affirming that it brought them closer to the reality of health care.

Conclusions

Simulation is a useful tool for the acquisition of skills in medication administration. The students were satisfied with the simulation capacity to bridge the gap between theory and practice. Moreover, simulation represents an added teaching resource in the nursing degree curriculum and is expected to enhance patient safety.
‘Leading from the front’ implementation increases the success of influenza vaccination drives among healthcare workers: a reanalysis of systematic review evidence using Intervention Component Analysis (ICA) and Qualitative Comparative Analysis (QCA)
Authors: Sutcliffe Katy , Kneale Dylan , Thomas James
Published: May 2022

Background

Seasonal influenza vaccination of healthcare workers (HCW) is widely recommended to protect staff and patients. A previous systematic review examined interventions to encourage uptake finding that hard mandates, such as loss of employment for non-vaccination, were more effective than soft mandates, such as signing a declination form, or other interventions such as incentives. Despite these overarching patterns the authors of the review concluded that ‘substantial heterogeneity’ remained requiring further analysis. This paper reanalyses the evidence using Intervention Component Analysis (ICA) and Qualitative Comparative Analysis (QCA) to examine whether the strategies used to implement interventions explain the residual heterogeneity.

Methods

We used ICA to extract implementation features and trialists’ reflections on what underpinned the success of the intervention they evaluated. The ICA findings then informed and structured two QCA analyses to systematically examine associations between implementation features and intervention outcomes. Analysis 1 examined hard mandate studies. Analysis 2 examined soft mandates and other interventions.

Results

In Analysis 1 ICA revealed the significance of ‘leading from the front’ rather than ‘top-down’ implementation of hard mandates. Four key features underpinned this: providing education prior to implementation; two-way engagement so HCW can voice concerns prior to implementation; previous use of other strategies so that institutions ‘don’t-go-in-cold’ with hard-mandates; and support from institutional leadership. QCA revealed that either of two configurations were associated with greater success of hard mandates. The first involves two-way engagement, leadership support and a ‘don’t-go-in-cold’ approach. The second involves leadership support, education and a ‘don’t-go-in-cold’ approach. Reapplying the ‘leading from the front’ theory in Analysis 2 revealed similar patterns.

Conclusions

Regardless of intervention type a ‘leading from the front’ approach to implementation will likely enhance intervention success. While the results pertain to flu vaccination among HCWs, the components identified here may be relevant to public health campaigns regarding COVID-19 vaccination.
Direct and indirect costs for hospitalized patients with dengue in Southern Sri Lanka
Authors: Weerasinghe N. P. , Bodinayake C. K. , Wijayaratne W. M. D. G. B. , Devasiri I. V. , Dahanayake N. J. , Kurukulasooriya M. R. P. , Premamali M. , Sheng T. , Nicholson B. P. , Ubeysekera H. A. , de Silva A. D. , Østbye T. , Woods C. W. , Tillekeratne L. G. , Nagahawatte A De S
Published: May 2022

Background

The Southern Province of Sri Lanka is endemic with dengue, with frequent outbreaks and occurrence of severe disease. However, the economic burden of dengue is poorly quantified. Therefore, we conducted a cost analysis to assess the direct and indirect costs associated with hospitalized patients with dengue to households and to the public healthcare system.

Methods

From June 2017–December 2018, we prospectively enrolled children and adults with acute dengue hospitalized at the largest, public tertiary-care (1800 bed) hospital in the Southern Province, Sri Lanka. We administered a structured questionnaire to obtain information regarding direct costs spent by households on medical visits, medications, laboratory testing, and travel for seeking care for the illness. Indirect costs lost by households were estimated by identifying the days of work lost by patients and caregivers and school days lost by children. Direct hospital costs were estimated using gross costing approach and adjusted by multiplying by annual inflation rates in Sri Lankan rupees and converted to US dollars.

Results

A total of 1064 patients with laboratory-confirmed dengue were enrolled. The mean age (SD) was 35.9 years (15.6) with male predominance (66.2%). The mean durations of hospitalization for adults and paediatric patients were 3.86 (SD = 1.51) and 4 (SD = 1.32) days, respectively. The per-capita direct cost borne by the healthcare system was 233.76 USD, and was approximately 14 times greater than the per-capita direct cost borne by households (16.29 USD, SD = 14.02). The per-capita average number of loss of working days was 21.51 (SD = 41.71), with mean per-capita loss of income due to loss of work being 303.99 USD (SD = 569.77), accounting for over 70% of average monthly income. On average, 10.88 days (SD = 10.97) of school days were missed due to the dengue episode. School misses were expected to reduce future annual income of affected children by 0.44%.

Conclusions

Dengue requiring hospitalization had a substantial economic burden on the public healthcare system in Sri Lanka and the affected households. These findings emphasize the importance of strengthening dengue control activities and improved use of hospital-based resources for care to reduce the economic impact of dengue in Sri Lanka.
Ten years of tracking mental health in refugee primary health care settings: an updated analysis of data from UNHCR’s Health Information System (2009–2018)
Authors: Fine Shoshanna L. , Kane Jeremy C. , Spiegel Paul B. , Tol Wietse A. , Ventevogel Peter
Published: May 2022

Background

This study examines mental, neurological, and substance use (MNS) service usage within refugee camp primary health care facilities in low- and middle-income countries (LMICs) by analyzing surveillance data from the United Nations High Commissioner for Refugees Health Information System (HIS). Such information is crucial for efforts to strengthen MNS services in primary health care settings for refugees in LMICs.

Methods

Data on 744,036 MNS visits were collected from 175 refugee camps across 24 countries between 2009 and 2018. The HIS documented primary health care visits for seven MNS categories: epilepsy/seizures, alcohol/substance use disorders, mental retardation/intellectual disability, psychotic disorders, severe emotional disorders, medically unexplained somatic complaints, and other psychological complaints. Combined data were stratified by 2-year period, country, sex, and age group. These data were then integrated with camp population data to generate MNS service utilization rates, calculated as MNS visits per 1000 persons per month.

Results

MNS service utilization rates remained broadly consistent throughout the 10-year period, with rates across all camps hovering around 2–3 visits per 1000 persons per month. The largest proportion of MNS visits were attributable to epilepsy/seizures (44.4%) and psychotic disorders (21.8%). There were wide variations in MNS service utilization rates and few consistent patterns over time at the country level. Across the 10 years, females had higher MNS service utilization rates than males, and rates were lower among children under five compared to those five and older.

Conclusions

Despite increased efforts to integrate MNS services into refugee primary health care settings over the past 10 years, there does not appear to be an increase in overall service utilization rates for MNS disorders within these settings. Healthcare service utilization rates are particularly low for common mental disorders such as depression, anxiety, post-traumatic stress disorder, and substance use. This may be related to different health-seeking behaviors for these disorders and because psychological services are often offered outside of formal health settings and consequently do not report to the HIS. Sustained and equitable investment to improve identification and holistic management of MNS disorders in refugee settings should remain a priority.
Immortalization effect of SV40T lentiviral vectors on canine corneal epithelial cells
Authors: Guo Long , Wang Zhihao , Li Jun , Li Jianji , Cui Luying , Dong Junsheng , Meng Xia , Qian Chen , Wang Heng
Published: May 2022

Background

Primary canine corneal epithelial cells (CCECs) easily become senescent, and cell proliferation is limited. Therefore, sampling for experimentation requires a large number of animals, which is problematic in terms of animal welfare and fails to maintain the stability of the cells for in vitro analyses.

Results

In this study, CCECs were separated and purified by trypsin and dispase II enzymatic analysis. Next, the cells were immortalized by transfection with a lentiviral vector expressing Simian vacuolating virus 40 large T (SV40T). The immortalized canine corneal epithelial cell line (CCEC-SV40T) was established by serial passages and monoclonal selection. The biological characteristics of CCEC-SV40T cells were evaluated based on the cell proliferation rate, cell cycle pattern, serum dependence, karyotype, and cytokeratin 12 immunofluorescence detection. In addition, we infected CCEC-SV40T cells with Staphylococcus pseudintermedius (S. pseudintermedius) and detected the inflammatory response of the cells. After the CCEC-SV40T cells were passaged continuously for 40 generations, the cells grew in a cobblestone pattern, which was similar to CCECs. The SV40T gene and cytokeratin 12 can be detected in each generation. CCEC-SV40T cells were observed to have a stronger proliferation capacity than CCECs. CCEC-SV40T cells maintained the same diploid karyotype and serum-dependent ability as CCECs. After CCEC-SV40T cells were infected with S. pseudintermedius, the mRNA expression levels of NLRP3, Caspase-1 and proinflammatory cytokines, including IL-1β, IL-6, IL-8 and TNF-α, were upregulated, and the protein levels of MyD88, NLRP3 and the phosphorylation of Iκbα and p65 were upregulated.

Conclusions

In conclusion, the CCEC-SV40T line was successfully established and can be used for in vitro studies, such as research on corneal diseases or drug screening.
MiR-129-5p exerts Wnt signaling-dependent tumor-suppressive functions in hepatocellular carcinoma by directly targeting hepatoma-derived growth factor HDGF
Authors: Huge Nicole , Reinkens Thea , Buurman Reena , Sandbothe Maria , Bergmann Anke , Wallaschek Hannah , Vajen Beate , Stalke Amelie , Decker Melanie , Eilers Marlies , Schäffer Vera , Dittrich-Breiholz Oliver , Gürlevik Engin , Kühnel Florian , Schlegelberger Brigitte , Illig Thomas , Skawran Britta
Published: May 2022

Background

In hepatocellular carcinoma (HCC), histone deacetylases (HDACs) are frequently overexpressed. This results in chromatin compaction and silencing of tumor-relevant genes and microRNAs. Modulation of microRNA expression is a potential treatment option for HCC. Therefore, we aimed to characterize the epigenetically regulated miR-129-5p regarding its functional effects and target genes to understand its relevance for HCC tumorigenesis.

Methods

Global miRNA expression of HCC cell lines (HLE, HLF, Huh7, HepG2, Hep3B) and normal liver cell lines (THLE-2, THLE-3) was analyzed after HDAC inhibition by miRNA sequencing. An in vivo xenograft mouse model and in vitro assays were used to investigate tumor-relevant functional effects following miR-129-5p transfection of HCC cells. To validate hepatoma-derived growth factor (HDGF) as a direct target gene of miR-129-5p, luciferase reporter assays were performed. Survival data andHDGFexpression were analyzed in public HCC datasets. After siRNA-mediated knockdown ofHDGF, its cancer-related functions were examined.

Results

HDAC inhibition induced the expression of miR-129-5p. Transfection of miR-129-5p increased the apoptosis of HCC cells, decreased proliferation, migration and ERK signaling in vitro and inhibited tumor growth in vivo.Direct binding of miR-129-5p to the 3′UTR ofHDGFvia a noncanonical binding site was validated by luciferase reporter assays.HDGFknockdown reduced cell viability and migration and increased apoptosis in Wnt-inactive HCC cells. These in vitro results were in line with the analysis of public HCC datasets showing thatHDGFoverexpression correlated with a worse survival prognosis, primarily in Wnt-inactive HCCs.

Conclusions

This study provides detailed insights into the regulatory network of the tumor-suppressive, epigenetically regulated miR-129-5p in HCC. Our results reveal for the first time that the therapeutic application of mir-129-5p may have significant implications for the personalized treatment of patients with Wnt-inactive, advanced HCC by directly regulatingHDGF. Therefore, miR-129-5p is a promising candidate for a microRNA replacement therapy to prevent HCC progression and tumor metastasis.
A novel nanobody as therapeutics target for EGFR-positive colorectal cancer therapy: exploring the effects of the nanobody on SW480 cells using proteomics approach
Authors: Lamtha Thomanai , Krobthong Sucheewin , Yingchutrakul Yodying , Samutrtai Pawitrabhorn , Gerner Christopher , Tabtimmai Lueacha , Choowongkomon Kiattawee
Published: May 2022

Background

The epidermal growth factor receptor (EGFR) overexpression is found in metastatic colorectal cancer (mCRC). Targeted molecular therapies such as monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKI) are becoming more precise, targeting specifically for cancer therapeutics. However, there are adverse effects of currently available anti-EGFR drugs, including drug-resistant and side effects. Nanobodies can overcome these limitations. Our previous study has found that cell-penetrable nanobodies targeted at EGFR-tyrosine kinase were significantly reduced EGFR-positive lung cancer cells viability and proliferation. The aim of the present study was to determine the effect of cell-penetrable nanobody (R9VH36) on cell viability and proteomic profile in EGFR-positive human colorectal cancer cell lines.

Methods

The human colorectal carcinoma cell line (SW480) was treated with R9VH36, compared with gefitinib. Cell viability was monitored using the MTT cell viability assay. The proteomic profiling was analyzed by LC–MS/MS .

Results

The half-maximal inhibitory concentration (IC50) values determined for R9VH36 and gefitinib against SW480 were 527 ± 0.03 nM and 13.31 ± 0.02 μM, respectively. Moreover, both the gefitinib-treated group and nanobody-treated group had completely different proteome profiles. A total 6626 differentially expressed proteins were identified. PCA analysis revealed different proteome profiling in R9VH36 experiment. There were 8 proteins in R9VH36 that significantly exhibited opposite expression directions when compared to gefitinib. These proteins are involved in DNA-damage checkpoint processes.

Conclusion

The proteomics explored those 6,626 proteins had different expressions between R9VH36 and gefitinib. There were 8 proteins in R9VH36 exhibited opposite expression direction when comparing to gefitinib. Our findings suggest that R9VH36 has the potential to be an alternative remedy for treating EGFR-positive colon cancer.
Evaluating official development assistance-funded granting mechanisms for global health and development research that is initiated in high-income countries
Authors: Cassola Adèle , Baral Prativa , Røttingen John-Arne , Hoffman Steven J.
Published: May 2022

Background

Several countries allocate official development assistance (ODA) for research on global health and development issues that is initiated in the donor country. The integration of such research within domestic research systems aligns with efforts to coordinate ODA investments with science, technology and innovation policies towards achieving the Sustainable Development Goals (SDGs).

Methods

Through a document synthesis and interviews with research funders in ODA donor and recipient countries, we evaluated the performance of this funding approach across seven donor-country programmes from five donor countries and examined the institutional design elements that increase its chances of advancing development goals and addressing global challenges.

Results

We found that carefully designed programmes provide a promising pathway to producing valuable and contextually relevant knowledge on global health and development issues. To achieve these outcomes and ensure they benefit ODA-receiving countries, programmes should focus on recipient-country priorities and absorptive capacity; translate research on global public goods into context-appropriate technologies; plan and monitor pathways to impact; structure equitable partnerships; strengthen individual and institutional capacity; and emphasize knowledge mobilization.

Conclusions

Global health and development research programmes and partnerships have an important role to play in achieving the SDGs and addressing global challenges. Governments should consider the potential of ODA-funded research programmes to address gaps in their global health and development frameworks. In the absence of concrete evidence of development impact, donor countries should consider making increases in ODA allocations for research additional to more direct investments that have demonstrated effectiveness in ODA-receiving countries.
Accelerometer-measured physical activity and sedentary time among children and their parents in the UK before and after COVID-19 lockdowns: a natural experiment
Authors: Salway Ruth , Foster Charlie , de Vocht Frank , Tibbitts Byron , Emm-Collison Lydia , House Danielle , Williams Joanna G. , Breheny Katie , Reid Tom , Walker Robert , Churchward Sarah , Hollingworth William , Jago Russell
Published: May 2022

Background

Restrictions due to the coronavirus disease 2019 (COVID-19) pandemic reduced physical activity provision for both children and their parents. Recent studies have reported decreases in physical activity levels during lockdown restrictions, but these were largely reliant on self-report methods, with data collected via unrepresentative self-report surveys. The post-pandemic impacts on children’s activity levels remain unknown. A key question is how active children become once lockdown restrictions are lifted.

Methods

Active-6 is a repeated cross-sectional natural experiment. Accelerometer data from 1296 children aged 10–11 and their parents were collected in 50 schools in the Greater Bristol area, UK in March 2017-May 2018 (pre-COVID-19 comparator group), and compared to 393 children aged 10–11 and parents in 23 of the same schools, collected in May-December 2021. Mean minutes of accelerometer-measured moderate-to-vigorous physical activity (MVPA) were derived for weekdays and weekend and compared pre- and post-lockdown via linear multilevel models.

Results

After adjusting for seasonality, accelerometer wear time and child/parent demographics, children’s mean weekday and weekend MVPA were 7.7 min (95% CI: 3.5 to 11.9) and 6.9 min (95% CI: 0.9 to 12.9) lower in 2021 than in 2018, respectively, while sedentary time was higher by 25.4 min (95% CI: 15.8 to 35.0) and 14.0 min (95% CI: 1.5 to 26.5). There was no evidence that differences varied by child gender or household education. There was no significant difference in parents’ MVPA or sedentary time, either on weekdays or weekends.

Conclusions

Children’s MVPA was lower by 7–8 min/day in 2021 once restrictions were lifted than before the pandemic for all groups, on both weekdays and weekends. Previous research has shown that there is an undesirable age-related decline in children’s physical activity. The 8-min difference reported here would be broadly comparable to the decline that would have previously been expected to occur over a three-year period. Parents’ physical activity was similar to pre-pandemic levels. Our results suggest that despite easing of restrictions, children’s activity levels have not returned to pre-pandemic levels. There is an urgent need to understand why these changes have occurred and how long they are maintained.
Interleukin 13 promotes long-term recovery after ischemic stroke by inhibiting the activation of STAT3
Authors: Chen Di , Li Jiaying , Huang Yichen , Wei Pengju , Miao Wanying , Yang Yaomei , Gao Yanqin
Published: May 2022

Background

Microglia/macrophages are activated after cerebral ischemic stroke and can contribute to either brain injury or recovery by polarizing microglia/macrophage into distinctive functional phenotypes with pro- or anti-inflammatory properties. Interleukin-13 (IL-13) is an anti-inflammatory cytokine that regulates microglia/macrophage polarization toward an anti-inflammatory phenotype. However, it is not clear whether IL-13 is beneficial after ischemic stroke long-term and the underlying molecular mechanism(s) remain unknown. Thus, we examined the effect of IL-13 on long-term recovery and microglia/macrophage polarization in mice with transient middle cerebral artery occlusion model (tMCAO).

Methods

tMCAO was induced in adult male C57BL/6J mice. IL-13 (60 μg/kg) was administered intranasally starting 2 h after stroke and continued for seven consecutive days. Sensorimotor function, spatial learning and memory function, as well as brain infarct volume were assessed up to 35 days after stroke. White matter integrity was evaluated by electrophysiology, immunofluorescence staining, and transmission electron microscopy. Microglia/macrophage activation was assessed using immunofluorescence staining and quantitative real-time polymerase chain reaction. Changes in immune cells in the brain and the periphery, and expression of IL-13 receptors in different brain cells were detected by flow cytometry. Primary neuron/microglia co-cultures and a STAT3 inhibitor were used for mechanistic studies.

Results

Post-treatment with IL-13 improved long-term neurofunctional recovery and decreased brain tissue atrophy after stroke. Intranasal delivery of IL-13 enhanced the structural and functional integrity of white matter after stroke. Furthermore, the neuroprotection afforded by IL-13 administration was not due to a direct effect on neurons, but by indirectly regulating the anti-inflammatory phenotype of microglia/macrophages. IL-13 treatment also had no effect on peripheral immune cells. Mechanistically, IL-13 improved the long-term outcome after ischemic stroke by promoting the polarization of microglia/macrophages toward the anti-inflammatory phenotype at least partially by inhibiting the phosphorylation of STAT3.

Conclusions

IL-13 promotes white matter repair and improves neurofunctional outcomes after ischemic stroke by modulating microglia/macrophages via inhibition of STAT3 phosphorylation.
Manual therapy versus advice to stay active for nonspecific back and/or neck pain: a cost-effectiveness analysis
Authors: Aboagye Emmanuel , Lilje Stina , Bengtsson Camilla , Peterson Anna , Persson Ulf , Skillgate Eva
Published: May 2022

Background

Low back and neck pain are the most common musculoskeletal disorders worldwide, and imply suffering and substantial societal costs, hence effective interventions are crucial. The aim of this study was to evaluate the cost-effectiveness of manual therapy compared with advice to stay active for working age persons with nonspecific back and/or neck pain.

Methods

The two interventions were: a maximum of 6 manual therapy sessions within 6 weeks, including spinal manipulation/mobilization, massage and stretching, performed by a naprapath (index group), respectively information from a physician on the importance to stay active and on how to cope with pain, according to evidence-based advice, at 2 occasions within 3 weeks (control group). A cost-effectiveness analysis with a societal perspective was performed alongside a randomized controlled trial including 409 persons followed for one year, in 2005. The outcomes were health-related Quality of Life (QoL) encoded from the SF-36 and pain intensity. Direct and indirect costs were calculated based on intervention and medication costs and sickness absence data. An incremental cost per health related QoL was calculated, and sensitivity analyses were performed.

Results

The difference in QoL gains was 0.007 (95% CI − 0.010 to 0.023) and the mean improvement in pain intensity was 0.6 (95% CI 0.068–1.065) in favor of manual therapy after one year. Concerning the QoL outcome, the differences in mean cost per person was estimated at − 437 EUR (95% CI − 1302 to 371) and for the pain outcome the difference was − 635 EUR (95% CI − 1587 to 246) in favor of manual therapy. The results indicate that manual therapy achieves better outcomes at lower costs compared with advice to stay active. The sensitivity analyses were consistent with the main results.

Conclusions

Our results indicate that manual therapy for nonspecific back and/or neck pain is slightly less costly and more beneficial than advice to stay active for this sample of working age persons. Since manual therapy treatment is at least as cost-effective as evidence-based advice from a physician, it may be recommended for neck and low back pain. Further health economic studies that may confirm those findings are warranted.

Trial registrationCurrent Controlled Trials ISRCTN56954776. Retrospectively registered 12 September 2006,http://www.isrctn.com/ISRCTN56954776.
Safety of surgical hip dislocation in femoral head fracture and dislocation (FHFD) and avascular necrosis risk factor analysis of FHFD: midterm results confirmed by SPECT/CT and MRI
Authors: Yoon Yong-Cheol , Oh Chang-Wug , Kim Joon-Woo , Heo Jeong , Song Hyung Keun
Published: May 2022

Background

The study aim was to report the treatment outcomes of trochanteric flip osteotomy (TFO) with surgical hip dislocation (SHD) for femoral head fracture and dislocation (FHFD) and to investigate the risk factors for avascular necrosis (AVN) of the femoral head.

Methods

The data of 34 patients (29 men, 5 women; mean age 37.9 years) diagnosed with FHFD and treated with TFO with SHD between May 2009 and February 2018 with an average follow-up period of 5.1 years (range 2.8–10.5 years) were analyzed. Clinical outcomes were evaluated using the Merle d'Aubigné–Postel score and Thompson–Epstein Scale. Radiologic outcomes were classified according to the Matta classification. AVN was confirmed using magnetic resonance imaging or single-photon emission computed tomography/computed tomography. The occurrence of complications was examined, and factors influencing complications, AVN.

Results

Regarding the Pipkin’s classification, there were 7 patients with type II, 2 patients with type III, and 25 patients with type IV fractures. Posterior wall fractures accompanied all associated acetabular fractures in the patients with Pipkin type IV fractures. Radiologically, the union of acetabular and femoral head fractures was observed within 6.1 months on average (range 4–10 months) in 32 patients, except two patients who developed femoral head AVN. Clinically, the average Merle d'Aubigné–Postel score was 14.4 points (range 8–17 points), and 22 patients had good or excellent results on the Thompson–Epstein Scale. Two patients developed femoral head AVN with both having displaced femoral neck fractures associated with FHFD. AVN was significantly correlated with femoral neck fractures (P = 0.000).

Conclusion

TFO with SHD is a safe and useful approach for the treatment of FHFD. Particular attention should be paid when treating femoral head fractures associated with displaced femoral neck fractures because of the high risk of AVN development.