bluuebunny/crossref_metadata_2025 huggingface dataset:
The NeoPACE study: study protocol for the development of a core outcome set for neonatal palliative care
Authors: Gallagher Katie , Chant Kathy , Mancini Alex , Bluebond-Langner Myra , Marlow Neil
Published: December 2023

Background

Neonatal death is the leading category of death in children under the age of 5 in the UK. Many babies die following decisions between parents and the neonatal team; when a baby is critically unwell, with the support of healthcare professionals, parents may make the decision to stop active treatment and focus on ensuring their baby has a ‘good’ death. There is very little evidence to support the clinical application of neonatal palliative care and/or end-of-life care, resulting in variation in clinical provision between neonatal units. Developing core outcomes for neonatal palliative care would enable the development of measures of good practice and enhance our care of families. The aim of this study is to develop a core outcome set with associated tools for measuring neonatal palliative care.

Method

This study has four phases: (1) identification of potential outcomes through systematic review and qualitative interviews with key stakeholders, including parents and healthcare professionals (2) an online Delphi process with key stakeholders to determine core outcomes (3) identification of outcome measures to support clinical application of outcome use (4) dissemination of the core outcome set for use across neonatal units in the UK. Key stakeholders include parents, healthcare professionals, and researchers with a background in neonatal palliative care.

Discussion

Developing a core outcome set will standardise minimum reported outcomes for future research and quality improvement projects designed to determine the effectiveness of interventions and clinical care during neonatal palliative and/or end-of-life care. The core outcome set will provide healthcare professionals working in neonatal palliative and/or end-of-life support with an increased and consistent evidence base to enhance practice in this area.

Trial registration

The study has been registered with the COMET initiative (https://www.comet-initiative.org/Studies/Details/1470) and the systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023451068).
Bilateral or unilateral tubo-ovarian abscess: exploring its clinical significance
Authors: Yagur Yael , Weitzner Omer , Shams Rebecca , Man-El Gili , Kadan Yfat , Daykan Yair , Klein Zvi , Schonman Ron
Published: December 2023

Objectives

To assess the characteristics of patients with unilateral and bilateral tubo-ovarian abscess (TOA).

Methods

Women diagnosed with TOA during 2003–2017 were included in this retrospective cohort study. TOA was diagnosed using sonography or computerized tomography and clinical criteria, or by surgical diagnosis. Demographics, sonographic data, clinical treatment, surgical treatment, and post-operative information were retrieved.

Results

The study cohort included 144 women who met the inclusion criteria, of whom 78 (54.2%) had unilateral TOA and 66 (45.8%) had bilateral TOA. Baseline characteristics were not different between the groups. There was a statistical trend that women with fewer events of previous PID were less likely to have with bilateral TOA (75.3% vs. 64.1%, respectively; p = 0.074). Women diagnosed with bilateral TOA were more likely to undergo surgical treratment for bilateral salpingo-oophorectomy compared to unilateral TOA (61.5% vs. 42.3%, respectively; p = 0.04). There was no difference in maximum TOA size between groups.

Conclusions

This study detected a trend toward increased need for surgical treatment in women diagnosed with bilateral TOA. These findings may contribute to determining the optimal medical or surgical treatment, potentially leading to a decrease in the duration of hospitalization, antibiotic exposure, and resistance. However, it is important to acknowledge that the results of the current study are limited, and further research is warranted to validate these potential outcomes.
Teaching point-of-care ultrasound using a serious game: a randomized controlled trial
Authors: Olgers Tycho , Rozendaal Jelle , van Weringh Sanne , van de Vliert Rachel , Laros Ranek , Bouma Hjalmar , ter Maaten Jan
Published: December 2023

Background

Point-of-care ultrasound (POCUS) is an important diagnostic tool for internists. However, there are important barriers in learning POCUS, including lack of practice time and lack of experts for supervision. Alternative learning tools may assist in overcoming these barriers. A serious game is being developed specifically for teaching ultrasound. In this study, we assessed the use of a serious game in learning POCUS.

Methods

Ultrasound-native medical students were randomly assigned to the intervention group (N = 27) or the control group (N = 26). Both groups performed a real ultrasound on a volunteer after a brief introduction, but the intervention group played a serious game in advance. The endpoints were the assessments of the videos by experts (scoring quality of the probe movements) and the research team (counting probe movements), and probe movements measured with an accelerometer.

Results

The intervention group completed the exam faster (247 s vs. 347 s, p = 0.006 (95% CI: [30.20;168.80]) and lifted the probe less frequently from the model (0.54 vs. 3.79, p = 0.001 (95% CI: [1.39;5.11]). Also, we found an in-game learning effect between levels, showing a 48% decrease in total playing time (p < 0.001), 36% reduction in attempts per coin (p = 0.007), a 33% reduction in total probe distance (p = 0.002), and a 61% decrease in contact moments (p < 0.001). However, there was no significant difference in expert score between the two groups.

Conclusion

The serious game ‘Underwater’ is a fun and useful addition to traditional bedside ultrasound learning, which also may overcome one of the most important barriers in learning ultrasound: lack of supervised practice time. We show that the game improves real-practice probe handling with faster and more goal-oriented probe movements.
GPRC5C regulates the composition of cilia in the olfactory system
Authors: Bhat Sneha , Dietz André , Senf Katja , Nietzsche Sandor , Hirabayashi Yoshio , Westermann Martin , Neuhaus Eva Maria
Published: December 2023

Background

Olfactory sensory neurons detect odourants via multiple long cilia that protrude from their dendritic endings. The G protein-coupled receptor GPRC5C was identified as part of the olfactory ciliary membrane proteome, but its function and localization is unknown.

Results

High-resolution confocal and electron microscopy revealed that GPRC5C is located at the base of sensory cilia in olfactory neurons, but not in primary cilia of immature neurons or stem cells. Additionally, GPRC5C localization in sensory cilia parallels cilia formation and follows the formation of the basal body. In closer examination, GPRC5C was found in the ciliary transition zone. GPRC5C deficiency altered the structure of sensory cilia and increased ciliary layer thickness. However, primary cilia were unaffected. Olfactory sensory neurons from Gprc5c-deficient mice exhibited altered localization of olfactory signalling cascade proteins, and of ciliary phosphatidylinositol-4,5-bisphosphat. Sensory neurons also exhibited increased neuronal activity as well as altered mitochondrial morphology, and knockout mice had an improved ability to detect food pellets based on smell.

Conclusions

Our study shows that GPRC5C regulates olfactory cilia composition and length, thereby controlling odour perception.
Self-collection of samples for group B streptococcus testing during pregnancy: a systematic review and meta-analysis
Authors: Borg Sarah A. , Cao Jenny , Nguyen Phi-Yen , Aziz Samia , Vogel Joshua P.
Published: December 2023

Background

Sample self-collection for reproductive tract infection diagnosis has been found to offer greater convenience, privacy, autonomy, and expanded access to testing in non-pregnant adults. This review aimed to determine whether sample self-collection is as accurate as provider-collection for detection of group B streptococcus colonisation in pregnancy and whether a strategy of self-collection compared to provider-collection might improve maternal and neonatal health outcomes.

Methods

We searched CINAHL Plus, Medline, EMBASE, Maternity and Infant Care Database, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews in June 2022. Eligible studies compared self-collected and provider-collected samples taken from the same participants or participants randomised to either self-collection or provider-collection for reproductive tract infection testing using the same test and testing method in pregnant individuals. We included trials and observational studies. Reviewers assessed risk of bias using the QUADAS-2 checklist and independently extracted data. Sensitivity and specificity for group B streptococcus colonisation of self-collected compared to provider-collected samples were pooled using a bivariate, random-effects, meta-analytic model. This review was registered with PROSPERO (CRD42023396573).

Results

The search identified 5909 references, of which eleven diagnostic accuracy group B streptococcus studies were included (n = 3269 participants). No studies assessed the effects of self-collection in pregnancy on health outcomes. All studies had high or unclear risk of bias. Pooled sensitivities of self-collected samples for group B streptococcus detection were 82% (95% CI: 66–91%; I2 = 68.85%) in four trials (n = 1226) and 91% (95% CI: 83–96%; I2 = 37.38%) in seven non-randomised studies (n = 2043). Pooled specificities were 99% (95% CI: 98–99%; I2 = 12.08%) and 97% (95% CI: 94–99%; I2 = 72.50%), respectively.

Conclusions

Self-collected samples for group B streptococcus detection in pregnancy had high specificity compared to provider-collection, but lower sensitivity, particularly for included trials. Studies investigating the effect of self-collection on health outcomes, and further higher quality trials comparing accuracy of self-collection to provider-collection, are required.
Effects of physical activity and sedentary time on depression, anxiety and well-being: a bidirectional Mendelian randomisation study
Authors: Casanova Francesco , O’Loughlin Jessica , Karageorgiou Vasilis , Beaumont Robin N. , Bowden Jack , Wood Andrew R. , Tyrrell Jessica
Published: December 2023

Background

Mental health conditions represent one of the major groups of non-transmissible diseases. Physical activity (PA) and sedentary time (ST) have been shown to affect mental health outcomes in opposite directions. In this study, we use accelerometery-derived measures of PA and ST from the UK Biobank (UKB) and depression, anxiety and well-being data from the UKB mental health questionnaire as well as published summary statistics to explore the causal associations between these phenotypes.

Methods

We used MRlap to test if objectively measured PA and ST associate with mental health outcomes using UKB data and summary statistics from published genome-wide association studies. We also tested for bidirectional associations. We performed sex stratified as well as sensitivity analyses.

Results

Genetically instrumented higher PA was associated with lower odds of depression (OR = 0.92; 95% CI: 0.88, 0.97) and depression severity (beta =  − 0.11; 95% CI: − 0.18, − 0.04), Genetically instrumented higher ST was associated higher odds of anxiety (OR = 2.59; 95% CI: 1.10, 4.60). PA was associated with higher well-being (beta = 0.11, 95% CI: 0.04; 0.18) and ST with lower well-being (beta =  − 0.18; 95% CI: − 0.32, − 0.03). Similar findings were observed when stratifying by sex. There was evidence for a bidirectional relationship, with higher genetic liability to depression associated with lower PA (beta =  − 0.25, 95% CI: − 0.42; − 0.08) and higher well-being associated with higher PA (beta = 0.15; 95% CI: 0.05, 0.25).

Conclusions

We have demonstrated the bidirectional effects of both PA and ST on a range of mental health outcomes using objectively measured predictors and MR methods for causal inference. Our findings support a causal role for PA and ST in the development of mental health problems and in affecting well-being.
Clinical prediction models and the multiverse of madness
Authors: Riley Richard D. , Pate Alexander , Dhiman Paula , Archer Lucinda , Martin Glen P. , Collins Gary S.
Published: December 2023

Background

Each year, thousands of clinical prediction models are developed to make predictions (e.g. estimated risk) to inform individual diagnosis and prognosis in healthcare. However, most are not reliable for use in clinical practice.

Main body

We discuss how the creation of a prediction model (e.g. using regression or machine learning methods) is dependent on the sample and size of data used to develop it—were a different sample of the same size used from the same overarching population, the developed model could be very different even when the same model development methods are used. In other words, for each model created, there exists a multiverse of other potential models for that sample size and, crucially, an individual’s predicted value (e.g. estimated risk) may vary greatly across this multiverse. The more an individual’s prediction varies across the multiverse, the greater the instability. We show how small development datasets lead to more different models in the multiverse, often with vastly unstable individual predictions, and explain how this can be exposed by using bootstrapping and presenting instability plots. We recommend healthcare researchers seek to use large model development datasets to reduce instability concerns. This is especially important to ensure reliability across subgroups and improve model fairness in practice.

Conclusions

Instability is concerning as an individual’s predicted value is used to guide their counselling, resource prioritisation, and clinical decision making. If different samples lead to different models with very different predictions for the same individual, then this should cast doubt into using a particular model for that individual. Therefore, visualising, quantifying and reporting the instability in individual-level predictions is essential when proposing a new model.
Early insulin resistance in normoglycemic low-risk individuals is associated with subclinical atherosclerosis
Authors: Iglesies-Grau Josep , Garcia-Alvarez Ana , Oliva Belén , Mendieta Guiomar , García-Lunar Inés , Fuster José J. , Devesa Ana , Pérez-Herreras Cristina , Fernández-Ortiz Antonio , Brugada Ramon , Ibanez Borja , Fernandez-Jimenez Rodrigo , Fuster Valentin
Published: December 2023

Background

Elevated glycated hemoglobin (HbA1c) is associated with a higher burden of subclinical atherosclerosis (SA). However, the association with SA of earlier insulin resistance markers is poorly understood. The study assessed the association between the homeostatic model assessment of insulin resistance index (HOMA-IR) and SA in addition to the effect of cardiovascular risk factors (CVRFs) in individuals with normal HbA1c.

Methods

A cohort of 3,741 middle-aged individuals from the Progression of Early Subclinical Atherosclerosis (PESA) study with basal HbA1c < 6.0% (< 42 mmol/mol) and no known CV disease underwent extensive imaging (multiterritorial vascular ultrasound and coronary artery calcium score, CACS) to assess the presence, burden, and extent of SA.

Results

Individuals with higher HOMA-IR values had higher rates of CVRFs. HOMA-IR showed a direct association with the multiterritorial extent of SA and CACS (p < 0.001) and with global plaque volume measured by 3-dimensional vascular ultrasound (p < 0.001). After adjusting for key CVRFs and HbA1c, HOMA-IR values ≥ 3 were associated with both the multiterritorial extent of SA (odds ratio 1.41; 95%CI: 1.01 to 1.95, p = 0.041) and CACS > 0 (odds ratio 1.74; 95%CI: 1.20 to 2.54, p = 0.004), as compared with the HOMA-IR < 2 (the reference HOMA-IR category). In a stratified analysis, this association remained significant in individuals with a low-to-moderate SCORE2 risk estimate (75.6% of the cohort) but not in high-risk individuals.

Conclusions

The use of HOMA-IR identified low-risk individuals with a higher burden of SA, after adjusting for the effects of key traditional CVRFs and HbA1c. HOMA-IR is a simple measure that could facilitate earlier implementation of primary CV prevention strategies in clinical practice.
Reprogramming mitochondrial metabolism of macrophages by miRNA-released microporous coatings to prevent peri-implantitis
Authors: Zhang Hongming , Yuan Yun , Xue Hanxiao , Yu Runping , Jin Xiayue , Wu Xiaolin , Huang Hui
Published: December 2023

Although various new biomaterials have enriched the methods for peri-implant inflammation treatment, their efficacy is still debated, and secondary operations on the implant area have also caused pain for patients. Recently, strategies that regulate macrophage polarization to prevent or even treat peri-implantitis have attracted increasing attention. Here, we prepared a laser-drilled and covered with metal organic framework-miR-27a agomir nanomembrane (L-MOF-agomir) implant, which could load and sustain the release of miR-27a agomir. In vitro, the L-MOF-agomir titanium plate promoted the repolarization of LPS-stimulated macrophages from M1 to M2, and the macrophage culture supernatant promoted BMSCs osteogenesis. In a ligation-induced rat peri-implantitis model, the L-MOF-agomir implants featured strong immunomodulatory activity of macrophage polarization and alleviated ligation-induced bone resorption. The mechanism of repolarization function may be that the L-MOF-agomir implants promote the macrophage mitochondrial function and metabolism reprogramming from glycolysis to oxidative phosphorylation. Our study demonstrates the feasibility of targeting cell metabolism to regulate macrophage immunity for peri-implantitis inhibition and provides a new perspective for the development of novel multifunctional implants.

Graphical Abstract
How the COVID-19 pandemic and related school closures reduce physical activity among children and adolescents in the WHO European Region: a systematic review and meta-analysis
Authors: Ludwig-Walz Helena , Siemens Waldemar , Heinisch Sarah , Dannheim Indra , Loss Julika , Bujard Martin
Published: December 2023

Background

Emerging research suggests that physical activity among children and adolescents decreased during the COVID-19 pandemic. However, a differentiated overview of European youth is lacking. In particular, no systematic analysis has been conducted to date on the impact of heterogeneous pandemic restrictions and school closures within European countries, and with regard to potentially vulnerable groups.

Methods

We searched seven databases and included studies for children and adolescents (≤ 19 years) of the WHO European Region that compared physical activity during the COVID-19 pandemic with a pre-pandemic baseline using validated measurement instruments. We used the Oxford Stringency Index and School Closure Index as indicators of restriction stringency. Screening for eligibility, data extraction, assessment of the study risk of bias (using the ‘Risk of Bias in Non-randomized Studies - of Exposure’ [ROBINS-E]) and certainty grading of evidence (using the GRADE approach), were all done in duplicate. Unpublished data was requested from study authors. Data were pooled in random effects models. An a priori protocol was published, reporting is carried out in accordance with the ‘Preferred Reporting Items for Systematic Review and Meta-Analyses’ (PRISMA) statement.

Results

Of 14,897 non-duplicate records, 26 publications (n = 15,038 pre-pandemic, n = 13,041 during pandemic) met full inclusion criteria. Comparison before and during the COVID-19 pandemic revealed a significant reduction in total physical activity (standardized mean difference [SMD], -0.57 [95%CI, -0.95; -0.20]) and moderate-to-vigorous physical activity (SMD, -0.43 [95% CI, -0.75; -0.10]), corresponding to a decrease of 12 min per day (a 20% reduction of the WHO recommendation). A decrease in sporting activity was also recorded. Subgroup analyses suggested that middle childhood (aged 8–12) and adolescents were particularly affected by the decline. School closures were associated with a reduction in physical activity. The certainty of evidence for all outcomes was low.

Conclusions

A sharp decline in all forms of physical activity was recorded among European children and adolescents during the COVID-19 pandemic. This decline was higher during periods of school closure and mainly affected younger schoolchildren and adolescents. Immediate action by policy-makers and practitioners, as well as evidence-based public health strategies, are imperative in reversing this trend.

Trial registration

PROSPERO: CRD42023395871
Phenylpropanoid-enriched broccoli seedling extract can reduce inflammatory markers and pain behavior
Authors: Gurgul Aleksandra A. , Najjar Yahya , Chee Ana , An Howard , Che Chun-Tao , Park Thomas J. , Warpeha Katherine M.
Published: December 2023

Background

Pain is a worldwide problem requiring an effective, affordable, non-addictive therapy. Using the edible plant broccoli, a growth protocol was developed to induce a concentrated combinatorial of potential anti-inflammatories in seedlings.

Methods

A growth method was utilized to produce a phenylpropanoid-rich broccoli sprout extract, referred to as Original Extract (OE). OE was concentrated and then resuspended for study of the effects on inflammation events. A rabbit disc model of inflammation and degeneration, and, a mouse model of pain behavior were used for in vivo and in vitro tests. To address aspects of mammalian metabolic processing, the OE was treated with the S9 liver microsome fraction derived from mouse, for use in a mouse in vivo study. Analytical chemistry was performed to identify major chemical species. Continuous variables were analyzed with a number of methods including ANOVA, and two-tailed t tests, as appropriate.

Results

In a rabbit spine (disc) injury model, inflammatory markers were reduced, and levels of regenerative markers were increased as a result of OE treatment, both in vivo and in vitro. In a mouse pain behavioral model, after treatment with S9 liver microsome fraction, the resultant extract significantly reduced early and late pain behavior in response to a pain stimulus. The OE itself reduced pain behavior in the mouse pain model, but did not achieve the level of significance observed for S9-treated extract. Analytical chemistry undertaken on the extract constituents revealed identities of the chemical species in OE, and how S9 liver microsome fraction treatment altered species identities and proportions.

Conclusions

In vitro and in vivo results indicate that the OE, and S9-treated OE broccoli extracts are worthwhile materials to develop a non-opiate inflammation and pain-reducing treatment.
Central activation of the fatty acid sensor GPR120 suppresses microglia reactivity and alleviates sickness- and anxiety-like behaviors
Authors: Nakajima Shingo , Demers Geneviève , Machuca-Parra Arturo Israel , Pour Zahra Dashtehei , Bairamian Diane , Bouyakdan Khalil , Fisette Alexandre , Kabahizi Anita , Robb Josephine , Rodaros Demetra , Laurent Cyril , Ferreira Guillaume , Arbour Nathalie , Alquier Thierry , Fulton Stephanie
Published: December 2023

G protein-coupled receptor 120 (GPR120, Ffar4) is a sensor for long-chain fatty acids including omega-3 polyunsaturated fatty acids (n-3 PUFAs) known for beneficial effects on inflammation, metabolism, and mood. GPR120 mediates the anti-inflammatory and insulin-sensitizing effects of n-3 PUFAs in peripheral tissues. The aim of this study was to determine the impact of GPR120 stimulation on microglial reactivity, neuroinflammation and sickness- and anxiety-like behaviors by acute proinflammatory insults. We found GPR120 mRNA to be enriched in  both murine and human microglia, and in situ hybridization revealed GPR120 expression in microglia of the nucleus accumbens (NAc) in mice. In a manner similar to or exceeding n-3 PUFAs, GPR120 agonism (Compound A, CpdA) strongly attenuated lipopolysaccharide (LPS)-induced proinflammatory marker expression in primary mouse microglia, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and inhibited nuclear factor-ĸB translocation to the nucleus. Central administration of CpdA to adult mice blunted LPS-induced hypolocomotion and anxiety-like behavior and reduced TNF-α, IL-1β and IBA-1 (microglia marker) mRNA in the NAc, a brain region modulating anxiety and motivation and implicated in neuroinflammation-induced mood deficits. GPR120 agonist pre-treatment attenuated NAc microglia reactivity and alleviated sickness-like behaviors elicited by central injection TNF-α and IL-1β. These findings suggest that microglial GPR120 contributes to neuroimmune regulation and behavioral changes in response to acute infection and elevated brain cytokines. GPR120 may participate in the protective action of n-3 PUFAs at the neural and behavioral level and offers potential as treatment target for neuroinflammatory conditions.
TNFR1 signaling converging on FGF14 controls neuronal hyperactivity and sickness behavior in experimental cerebral malaria
Authors: Dvorak Nolan M. , Domingo Nadia D. , Tapia Cynthia M. , Wadsworth Paul A. , Marosi Mate , Avchalumov Yosef , Fongsaran Chanida , Koff Leandra , Di Re Jessica , Sampson Catherine M. , Baumgartner Timothy J. , Wang Pingyuan , Villarreal Paula P. , Solomon Olivia D. , Stutz Sonja J. , Aditi  , Porter Jacob , Gbedande Komi , Prideaux Brendan , Green Thomas A. , Seeley Erin H. , Samir Parimal , Dineley Kelley T. , Vargas Gracie , Zhou Jia , Cisneros Irma , Stephens Robin , Laezza Fernanda
Published: December 2023

Background

Excess tumor necrosis factor (TNF) is implicated in the pathogenesis of hyperinflammatory experimental cerebral malaria (eCM), including gliosis, increased levels of fibrin(ogen) in the brain, behavioral changes, and mortality. However, the role of TNF in eCM within the brain parenchyma, particularly directly on neurons, remains underdefined. Here, we investigate electrophysiological consequences of eCM on neuronal excitability and cell signaling mechanisms that contribute to observed phenotypes.

Methods

The split-luciferase complementation assay (LCA) was used to investigate cell signaling mechanisms downstream of tumor necrosis factor receptor 1 (TNFR1) that could contribute to changes in neuronal excitability in eCM. Whole-cell patch-clamp electrophysiology was performed in brain slices from eCM mice to elucidate consequences of infection on CA1 pyramidal neuron excitability and cell signaling mechanisms that contribute to observed phenotypes. Involvement of identified signaling molecules in mediating behavioral changes and sickness behavior observed in eCM were investigated in vivo using genetic silencing.

Results

Exploring signaling mechanisms that underlie TNF-induced effects on neuronal excitability, we found that the complex assembly of fibroblast growth factor 14 (FGF14) and the voltage-gated Na+ (Nav) channel 1.6 (Nav1.6) is increased upon tumor necrosis factor receptor 1 (TNFR1) stimulation via Janus Kinase 2 (JAK2). On account of the dependency of hyperinflammatory experimental cerebral malaria (eCM) on TNF, we performed patch-clamp studies in slices from eCM mice and showed that Plasmodium chabaudi infection augments Nav1.6 channel conductance of CA1 pyramidal neurons through the TNFR1–JAK2–FGF14–Nav1.6 signaling network, which leads to hyperexcitability. Hyperexcitability of CA1 pyramidal neurons caused by infection was mitigated via an anti-TNF antibody and genetic silencing of FGF14 in CA1. Furthermore, knockdown of FGF14 in CA1 reduced sickness behavior caused by infection.

Conclusions

FGF14 may represent a therapeutic target for mitigating consequences of TNF-mediated neuroinflammation.
Effects of hormonal contraceptives on lipid profile among women attending family planning unit in Goba Town Public Health Facilities, Bale, Southeast Ethiopia: a comparative cross-sectional study
Authors: Turki Awel , Ayalew Almaz , Mossie Andualem , Mitiku Shimelis
Published: December 2023

Background

Hormonal contraceptives are a widely used contraceptive method for the prevention of pregnancy in women. It is associated with change in lipid profile which results in congestive heart failure, coronary heart disease, angina, deep vein thrombosis and stroke which are the major cause of premature death. We aim to investigate the effects of hormonal contraceptive use on lipid profile among women attending family planning unit in Goba Town Public Health Facilities.

Methods

A comparative cross-sectional study design was conducted on 93 hormonal contraceptive users and 93 non-users’ women in Goba Town Public Health Facilities from September to November, 2022. Blood samples for the estimation of TC, TG, HDL-c and LDL-c levels were collected. Student's independent t-test was used to compare the results of lipid profiles. One-way ANOVA was used to identify the variation of lipid profile between progestin only pills, DMPA and implant users. Simple linear regression was used to determine the change in lipid profiles in relation to the duration of hormonal contraceptive use. P-value less than 0.05 was considered as statistically significant.

Result

The mean serum level of TC, TG and LDL-c was significantly increases in hormonal contraceptive users in comparison with non-users. The mean serum level TC, TG, LDL-c and HDL-c was significantly different between DMPA, implanon and POP users. The mean serum level of TC, TG and LDL-c in implanon users was lower than DMPA and POP users. As the duration of DMPA and POP use increases, the serum level of TC, TG and LDL-c were significantly increased. But, the serum level of HDL-c was significantly decreased. LDL-c was significantly increased with the duration of implanon use.

Conclusion

The mean serum level of TC, TG and LDL-c were significantly increased among hormonal contraceptive users. The mean serum level of lipid profile was significantly different between DMPA, implanon and POP users. The serum level of TC, TG, LDL-c were directly proportional to the duration of DMPA and POP use. Routine evaluation of lipid profiles is advisable before and after initiation of hormonal contraceptives.
Biomechanical comparison of different fixation methods in tibiotalocalcaneal arthrodesis: a cadaver study
Authors: Trost Matthias , Yarkin Suzan , Knieps Matthias , Frey Sönke , Neiss Wolfram Friedrich , Eysel Peer , Gick Sascha , Dargel Jens
Published: December 2023

Background

Various fixation methods are available for tibiotalocalcaneal arthrodesis: nail, plate, or screws. An intramedullary bone stabilization system within a balloon catheter has not previously been used in tibiotalocalcaneal arthrodesis. The aim of this study was to compare the stability of these techniques.

Methods

Twenty-four lower legs from fresh-frozen human cadavers were used. Tibiotalocalcaneal arthrodesis was performed with a retrograde nail, a lateral locking plate, three cancellous screws, or an intramedullary bone stabilization system. The ankles were loaded cyclically in plantarflexion and dorsiflexion.

Results

For cyclic loading at 125 N, the mean range of motion was 1.7 mm for nail, 2.2 mm for plate, 6.0 mm for screws, and 9.0 mm for the bone stabilization system (P < .01). For cyclic loading at 250 N, the mean range of motion was 4.4 mm for nail, 7.5 mm for plate, 12.1 mm for screws, and 14.6 mm for the bone stabilization system (P < .01). The mean cycle of failure was 4191 for nail, 3553 for plate, 3725 for screws, and 2132 for the bone stabilization system (P = .10).

Conclusions

The stability of the tibiotalocalcaneal arthrodesis differs depending on the fixation method, with nail or plate showing the greatest stability and the bone stabilization system the least. When three screws are used for tibiotalocalcaneal arthrodesis, the stability is intermediate. As the biomechanical stability of the bone stabilization system is low, it cannot be recommended for tibiotalocalcaneal arthrodesis.
Efficacy and safety of voriconazole in the treatment of invasive pulmonary aspergillosis in patients with liver failure: study protocol for a randomized controlled clinical trial
Authors: Yu Xue , Xu Lejia , Zheng Jiaxing , Lei Ziying , Pang Yihua , Li Xiaojie , Zhu Jianyun , Liu Jing
Published: December 2023

Background

Acute-on-chronic liver failure (ACLF) is a common clinical type of liver failure, and patients with acute-on-chronic liver failure are prone to fungal infections, especially the increasing incidence of invasive pulmonary aspergillosis (IPA). Voriconazole is recommended as the first-line antifungal agent in the treatment of invasive aspergillosis; however, no recommendation has been given for patients with severe liver cirrhosis (Child–Pugh C) and liver failure. This trial aims to examine the therapeutic effects and safety of voriconazole in the treatment of IPA in patients with liver failure.

Methods

This study is a non-double-blind randomized controlled trial. The 96 eligible acute-on-chronic liver failure patients complicated with invasive pulmonary aspergillosis will be randomly assigned to receive either the optimized voriconazole regimen or the recommended voriconazole regimen for patients with mild to moderate liver cirrhosis (Child–Pugh A and B), at a 1:1 ratio, with an 8-week follow-up period. The antifungal efficacy of voriconazole will be the primary outcome measure. Plasma voriconazole trough concentration, the laboratory examination (CRP, PCT, ESR, etc.), chest CT, adverse events, and mortality at week 4 and 8 will be the secondary outcome measures.

Discussion

This trial aims to demonstrate the efficacy and safety of voriconazole in the treatment of IPA in patients with liver failure, which is expected to provide a reference for scientific optimization of voriconazole regimens and a realistic basis for the standardized treatment of acute-on-chronic liver failure patients complicated with invasive pulmonary aspergillosis.

Trial registration

The trial was registered with the Chinese Clinical Trial Registry, ChiCTR2100048259. Registered on 5 July 2021.
Association between non-high-density lipoprotein to high-density lipoprotein ratio and reversion to normoglycemia in people with impaired fasting glucose: a 5-year retrospective cohort study
Authors: Mo Zihe , Han Yong , Cao Changchun , Huang Qingli , Hu Yanhua , Yu Zhiqun , Hu Haofei
Published: December 2023

Objective

The relationship between the non-high-density lipoprotein to high-density lipoprotein ratio (non-HDL-c/HDL-c ratio) and changes in glycemic status as well as the development of type 2 diabetes mellitus (T2DM) has been well established. However, there is a lack of evidence concerning the association between the non-HDL-c/HDL-c ratio and the reversal of normoglycemia in individuals with impaired fasting glucose (IFG). Therefore, this study aimed to examine the connection between the non-HDL-c/HDL-c ratio and the likelihood of reverting to normoglycemia among people with IFG.

Methods

This retrospective cohort study examined data collected from 15,524 non-selective participants with IFG at the Rich Healthcare Group in China between January 2010 and 2016. The Cox proportional-hazards regression model was used to investigate the connection between the baseline non-HDL-c/HDL-c ratio and the probability of reverting to normoglycemia. We were able to discover the non-linear association between the non-HDL-c/HDL-c ratio and reversion to normoglycemia using a Cox proportional hazards regression model with cubical spline smoothing. We also performed several sensitivity and subgroup analyses. A competing risk multivariate Cox regression was utilized as well to examine the development to diabetes as a competing risk for the reversal of normoglycemic events.

Results

In our study, a total of 15,524 individuals participated, with a mean age of 50.9 ± 13.5 years, and 64.7% were male. The average baseline non-HDL-c/HDL-c ratio was 2.9 ± 0.9. Over a median follow-up period of 2.9 years, we observed a reversion rate to normoglycemia of 41.8%. After adjusting for covariates, our findings revealed a negative association between the non-HDL-c/HDL-c ratio and the likelihood of reverting to normoglycemia (HR = 0.71, 95% CI 0.69–0.74). Notably, we identified a non-linear relationship between the non-HDL-c/HDL-c ratio and the probability of transitioning from IFG to normoglycemia. We found an inflection point at a non-HDL-c/HDL-c ratio of 3.1, with HRs of 0.63 (95% CI 0.69, 0.74) on the left side and 0.78 (95% CI 0.74, 0.83) on the right side of the point. Competing risks multivariate Cox's regression, sensitivity analysis, and subgroup analysis consistently supported our robust results.

Conclusion

Our study has revealed a negative and non-linear relationship between the non-HDL-c/HDL-c ratio and reversion to normoglycemia in Chinese people with IFG. Specifically, when the non-HDL-c/HDL-c ratio was below 3.1, a significant and negative association with reversion to normoglycemia was observed. Furthermore, keeping the non-HDL-c/HDL-c ratio below 3.1 significantly elevated the probability of returning to normoglycemia.
Associations between HT, BMI, and allergic rhinitis in perimenopausal women
Authors: Liu Jingyi , Ma Tingting , Wang Xiaoxue , Bai Wenpei , Wang Xueyan
Published: December 2023

Background

Increasing evidence suggests that hormone therapy (HT) and obesity exert an influence on allergic rhinitis (AR). It is important to investigate the association and interactions between HT, BMI, and AR in perimenopausal women.

Methods

From May 2020 to March 2021, a cross-sectional survey was completed by patients who visited the Allergy Department and Gynecology Department of Shijitan Hospital. The patients completed a questionnaire and stratified analyses by BMI in tertiles were performed. Logistic analyses were performed to evaluate the relationships between HT, BMI, and AR.

Results

A total of 950 patients completed the study, among which, 393 patients were receiving HT. HT was found to be associated with increased risks for AR (OR = 1.51 [95% CI: 1.151–1.985]), asthma (OR = 3.61 [95% CI: 2.21–5.89]), and their accompanying symptoms (OR = 3.54 [95% CI: 2.146–5.831]). In lean women, the use of HT was significantly associated with a higher risks for AR (OR = 2.26 [95% CI: 1.31–3.91]), the time course of AR (OR = 2.54 [95% CI: 1.37–4.74]), hay fever (OR = 2.54 [95% CI: 1.37–4.74]), and accompanying symptoms (including canker sores, diarrhea, and stomachache) (OR = 2.26 [95% CI: 1.309–3.907]) when compared to normal or heavier weight women (course of AR: pinteraction = 0.032; hay fever; pinteraction = 0.006; accompanying symptoms: pinteraction = 0.009).

Conclusions

HT can reduce the risk for AR in perimenopausal women. Lean women who used HT were at a higher risk for AR when compared to overweight women who used AR. There exists an interaction between HT and BMI that influences AR. Furthermore, HT and obesity increase the risk for AR by some common pathways, more follow-up work is needed to explore common pathways.
Mitochondrial dysfunction induced by bedaquiline as an anti-Toxoplasma alternative
Authors: Shi Yuehong , Jiang Yucong , Qiu Haolong , Hu Dandan , Song Xingju
Published: December 2023

Toxoplasma gondii is a zoonotic parasite that infects one-third of the world’s population and nearly all warm-blooded animals. Due to the complexity of T. gondii’s life cycle, available treatment options have limited efficacy. Thus, there is an urgent need to develop new compounds or repurpose existing drugs with potent anti-Toxoplasma activity. This study demonstrates that bedaquiline (BDQ), an FDA-approved diarylquinoline antimycobacterial drug for the treatment of tuberculosis, potently inhibits the tachyzoites of T. gondii. At a safe concentration, BDQ displayed a dose-dependent inhibition on T. gondii growth with a half-maximal effective concentration (EC50) of 4.95 μM. Treatment with BDQ significantly suppressed the proliferation of T. gondii tachyzoites in the host cell, while the invasion ability of the parasite was not affected. BDQ incubation shrunk the mitochondrial structure and decreased the mitochondrial membrane potential and ATP level of T. gondii parasites. In addition, BDQ induced elevated ROS and led to autophagy in the parasite. By transcriptomic analysis, we found that oxidative phosphorylation pathway genes were significantly disturbed by BDQ-treated parasites. More importantly, BDQ significantly reduces brain cysts for the chronically infected mice. These results suggest that BDQ has potent anti-T. gondii activity and may impair its mitochondrial function by affecting proton transport. This study provides bedaquiline as a potential alternative drug for the treatment of toxoplasmosis, and our findings may facilitate the development of new effective drugs for the treatment of toxoplasmosis.
In vitro ruminal-microbial fermentation pattern: nutritional insights about some agricultural crop mesocarps (peel) in ruminant nutrition
Authors: Kazemi Mohsen
Published: December 2023

Different agricultural crop wastes (ACW) such as mesocarps (peel) are annually produced after consuming their edible parts in the world without any scientific information about their nutritional potential. Therefore, a study was conducted to determine the ruminal-microbial fermentation pattern and nutritional potential of some crop mesocarps (peel) including different species of melons (Watermelon, Galia melon, Rockmelon, Til sabz, and Til atashi) as well as cucumber and eggplant using common and standard laboratory methods. The amount of crude protein (CP) varied from 7.19 to 19.1% of dry matter (DM) for Til sabz and cucumber mesocarps, respectively. The highest (34.1% of DM) and lowest (15.4%) content of neutral detergent fiber (NDF) were related to eggplant and Til sabz peels, respectively (p < 0.05). The content of non-fiber carbohydrates (NFC) varied from 38.7% for eggplant peel to 66.6% for Til sabz. All mesocarps had a low DM percentage (4.88% of DM for cucumber to 8.45 for eggplant). Rockmelon peel had the highest amount of calcium (5.25 g/kg DM) and magnesium (5.75 g/kg DM) compared with the other mesocarps (p < 0.05). The highest amounts of potassium (33.4 g/kg of DM), sodium (7.15 g/kg of DM), and zinc (21 mg/kg of DM) were observed in the peels of watermelon, Til atashi, and cucumber, respectively (p < 0.05). The potential of ruminal-microbial gas production also differed from 55.6 ml/200 mg of DM for eggplant to 63.1 ml for Til sabz peel. Except for cucumber (8.75 MJ/kg of DM) and eggplant (8.71 MJ), other mesocarps (different melon species) had almost similar metabolizable energy (ME, 9.06–9.50 MJ/kg of DM). Among the studied mesocarps, the lowest ruminal-microbial DM and organic matter (OM) digestibility was also observed in eggplant and cucumber (p < 0.05). Gallia melon had the highest acid-base buffering capacity (267 mEq×10− 3,p < 0.05). According to our findings, the mesocarps of melons showed a higher nutritional value than the cucumber and eggplant. In general, Til sabz exhibited a notable favorite and superior nutritional characteristic compared with the other mesocarps.
Enrichment and toxic effects of triclosan on aquatic macrophytes Eichhornia crassipes and Hydrilla verticillata exposed to triclosan in sediments
Authors: Yan Xiuxiu , Hu Fangyu , An Jing , Yin Yongchao , Zhang Lingyan , Wei Shuhe
Published: December 2023

Background

Clarifying the enrichment and response processes of triclosan (TCS) in hydrophytes is crucial for assessing the ecological risk of TCS in aquatic environments. This study delves into the chronic toxic effects of TCS in floating plant Eichhornia crassipes (Mart.) Solms and submerged plant Hydrilla verticillata (L. f.) Royle exposed to TCS sediments through hydroponic experiments.

Results

The absorption abilities of hydrophytes to TCS were species-dependent. The concentration of TCS in the roots of E. crassipes was significantly higher than that in its leaves, while the absorption capacities of the leaves of H. verticillata to TCS were stronger than that in its roots. Furthermore, the physiological indexes, including chlorophyll concentration, soluble protein concentration, and antioxidant enzyme activities, showed a significant decrease with the exposure concentration and time of TCS. Although the chlorophyll and soluble protein concentrations and the antioxidant enzyme activities in the leaves were initially increased at a low concentration of TCS (at 7 days of exposure), they decreased significantly over time. Compared to the leaves, the physiological indexes of the roots were more sensitive to the ecotoxicological effects of TCS. The inhibition effects of TCS on H. verticillata were significantly higher than those on E. crassipes, which may be associated with the absorbing abilities of TCS and the growth characteristics of the plants. Pearson’s correlation analysis found a significant negative correlation between the TCS concentrations and the antioxidant enzyme activities in the plants.

Conclusions

This study highlighted the differences in the uptake and enrichment process and toxic effects of TCS by different aquatic plants. Compared with E. crassipes, H. verticillata is more sensitive to TCS toxicity.
Healthcare‑associated infections in intensive care unit patients with and without COVID-19: a single center prospective surveillance study
Authors: Bloch Nando , Rüfenacht Susanne , Ludwinek Magdalena , Frick Waldemar , Kleger Gian-Reto , Schneider Florian , Albrich Werner C. , Flury Domenica , Kuster Stefan P , Schlegel Matthias , Kohler Philipp
Published: December 2023

Background

The coronavirus disease 2019 (COVID-19) pandemic led to a global increase in healthcare-associated infections (HAI) among intensive care unit (ICU) patients. Whether this increase is directly attributable to COVID-19 or whether the pandemic indirectly (via staff shortages or breaches in infection prevention measures) led to this increase, remains unclear. The objectives of this study were to assess HAI incidence and to identify independent risk factors for HAI in COVID-19 and non-COVID-19 ICU patients.

Methods

We established a monocentric prospective HAI surveillance in the medical ICU of our tertiary care center from September 1st 2021 until August 31st 2022, during circulation of the SARS-CoV-2 delta and omicron variants. We consecutively included patients ≥ 18 years of age with an ICU length of stay of > 2 calendar days. HAI were defined according to the European Centre for Disease Prevention and Control definitions. HAI rate was calculated per 1,000 patient-days or device-days; risk ratios (RR) and corresponding 95% confidence intervals (CI) for COVID-19 versus non-COVID-19 patients were calculated. We used multivariable Cox regression to identify independent risk factors for HAI. As a proxy for institutional COVID-19 burden, weekly COVID-19 density (i.e. percentage of COVID-19 patients among all ICU patients) was included in the model as time-dependent co-variable.

Results

We included 254 patients, 64 (25.1%) COVID-19 and 190 (74.9%) non-COVID-19 patients; 83 HAI in 72 patients were recorded, thereof 45 ventilator-associated lower respiratory tract infections (VA-LRTI) (54.2%) and 18 blood stream infections (BSI) (21.6%). HAI incidence rate was 49.1/1,000 patient-days in COVID-19 and 22.5/1,000 patient-days in non-COVID-19 patients (RR 2.2, 95%-CI 1.4–3.4). This result was mainly due to different VA-LRTI rates (40.3 vs. 11.7/1,000 ventilator days, p < 0.001), whereas BSI rates were not statistically different (9.4 vs. 5.6/1,000 patient days, p = 0.27). Multivariable analysis identified COVID-19 as main risk factor for HAI development, whereas age, mechanical ventilation and COVID-19 density were not significant.

Conclusions

These data from the fourth and fifth wave of the pandemic show a higher HAI incidence in COVID-19 than in non-COVID-19 ICU patients, mainly due to an increase in pulmonary infections. A diagnosis of COVID-19 was independently associated with HAI development, whereas institutional COVID-19 burden was not.