bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Systemic Hormonal Contraceptives With Reconstruction Procedures for Patellar Instability
Authors: Martinazzi Brandon J. , Bertha Nicholas , Nam Hannah H. , Lorenz F. Jeffrey , Bonaddio Vincenzo , Ptasinski Anna , Gallo Robert A.
Published: October 2023

Background:

Previous research suggests that estrogen plays a role in increased ligamentous laxity observed within the female population. Whereas many studies have sought to evaluate the impact of exogenous estrogen on anterior cruciate ligament injuries, research has not yet explored its impact on the medial patellofemoral ligament. Furthermore, less is known about the role of exogenous progesterone on ligamentous structures.

Purpose:

To determine whether women prescribed systemic estrogen (ethinyl estradiol) or progesterone (norgestimate or etonogestrel) hormonal contraceptives had an increased risk of undergoing reconstruction surgery for patellar instability compared with women without a prescription for systemic hormonal contraceptives.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

The TriNetX Research Network database was queried using International Classification of Disease and Common Procedural Terminology codes for women aged 15 to 26 years who underwent reconstruction procedures for patellar instability between 2012 and 2022. Women were grouped according to whether they had a coded prescription for a systemic hormonal contraceptive containing either ethinyl estradiol or etonogestrel; controls were matched by age, sex, race, and ethnicity. The relative risk (RR) of undergoing reconstruction for patellar instability was determined for each contraceptive.

Results:

After 1-to-1 propensity score matching, 0.054% (525/980,878) of women prescribed a systemic contraceptive containing ethinyl estradiol underwent reconstruction procedures for patellar instability compared with 0.043% (417/980,878) of controls (RR, 1.3; 95% CI, 1.1-1.4; P = .0004). Likewise, 0.058% (67/116,260) of women prescribed a form of systemic contraceptive containing only etonogestrel underwent reconstruction procedures for patellar instability compared with 0.026% (30/116,260) of controls (RR, 2.2; 95% CI, 1.5-3.4; P = .0002).

Conclusion:

Female patients prescribed systemic contraceptives containing estrogen or progesterone had an increased rate of reconstruction procedures for patellar instability.
Epilepsia Partialis Continua that Improved in a Pediatric Patient with Sub-dural Empyema
Authors: Schall J. , Ahmad S. , Avula S.
Published: October 2023

In epilepsia partialis continua (EPC), the EEG tracings may fail to show epileptiform activity because the electrical activity is too subtle or too deep to be picked up by surface electrodes. EPC can occur at any age and may have many etiologies, including genetic, metabolic, structural, infectious, and idiopathic. Typical EEG in EPC is characterized by discharges of cortical origin that commonly consist of sharp waves, spikes or periodic lateralized epileptiform discharge; however, EEG findings at large are variable and often not even identified. Here we present a pediatric case of EPC in the setting of subdural empyema with atypical EEG seizure associated with focal clonic activity who made rapid improvements.
“Recovering” the political: Unpacking the implications of (de)politicization for the transformative capacities of urban experiments
Authors: Sierhuis Darren , Bertolini Luca , Van Winden Willem
Published: October 2023

In many European cities, urban experimentation is increasingly preferred as a method for testing and disseminating innovations that might ignite a transformation toward more sustainable cities. By both academics and practitioners, these experiments tend to be approached as relatively neutral initiatives through which plural urban stakeholders willfully collaborate, while their success is seen as above all dependent on effective management. For this reason, the political nature of urban experiments, in the sense that they entangle different and often contending stakeholders in their innovation processes, remains relatively unarticulated in both practice and the academic literature. Building on the urban experimentation literature and political theory, this conceptual paper argues that the depoliticization of experimental initiatives is especially problematic for unleashing their transformative potential, which requires revealing the existing power-relations and biases keeping the status quo in place and negotiability of radical alternatives. From this perspective, the paper sketches out four ideal-typical trajectories for experiments as related to their (de)politicization; optimization, blind leap, antagonistic conflict and transformation. Bringing insights from political theory to bear on the urban experimentation literature, we proceed to hypothesize the implications of our ideal-types for urban experiments’ transformative capacities. The paper closes by presenting a future research and policy agenda.
Incidence of Craniofacial Trauma Changes With the Seasons
Authors: Wilkins Sarah G. , Shah Hemali P. , Bourdillon Alexandra T. , Salehi Parsa P. , Steren Benjamin , Sawan Tareq , Torabi Sina J. , Lee Yan Ho
Published: October 2023

Objective:

Craniofacial fractures are commonly attributed to exposures that may vary with seasons. While it is commonly thought that summer months tend to have more craniofacial trauma, exact seasonality of such traumas across anatomic sites have not yet been elucidated. We aimed to characterize trends of craniofacial trauma across seasons.

Study Design:

Retrospective medical record review.

Setting:

Single-institution study at Level 1 trauma center.

Methods:

Patient and admission data for craniofacial trauma from June 2013 to June 2019 were systematically extracted by the hospital analyst team using International Classification of Diseases, 10th edition (ICD-10) diagnosis codes. For each ICD-10 diagnosis, anatomic sites affected by trauma were categorized. Trends across seasons and injury site were investigated using Student’s t-test and analysis of variance (ANOVA).

Results:

Across 925 admissions that met inclusion criteria, the volume of admissions did not significantly differ by season (ANOVA: P = .33). Frequency of admissions for jaw and maxilla fractures was significantly lower in the winter compared to summer (jaw: P = .024; maxilla: P = .018). Number of admissions involving zygoma fractures was lower in the winter compared to summer ( P = .044) and compared to fall ( P = .028). When examining number of fracture sites (eg, 1, 2, or ≥3) for each admission, there was a significantly greater number of admissions with ≥3 fracture sites during summer compared to winter ( P = .017) and fall compared to winter ( P = .011).

Conclusion:

Rates of craniofacial trauma admissions appear to follow seasonal trends, with significantly fewer craniofacial trauma presentations during winter when compared to summer, especially among non-occipital injuries. These findings, along with future efforts to elucidate seasonal trends nationally, may enable forecasting patterns of fractures to better guide resource allocation and inform prevention strategies.
Genome editing of patient-derived iPSCs identifies a deep intronic variant causing aberrant splicing in hemophilia A
Authors: Hiramoto Takafumi , Inaba Hiroshi , Baatartsogt Nemekhbayar , Kashiwakura Yuji , Hayakawa Morisada , Kamoshita Nobuhiko , Nishimasu Hiroshi , Nureki Osamu , Kinai Ei , Ohmori Tsukasa
Published: October 2023

The importance of genetic diagnosis for patients with hemophilia has been recently demonstrated. However, the pathological variant cannot be identified in some patients. Here, we aimed to identify the pathogenic intronic variant causing hemophilia A using induced pluripotent stem cells (iPSCs) from patients and genome editing. We analyzed siblings with moderate hemophilia A and without abnormalities in the F8 exon. Next-generation sequencing of the entire F8 revealed 23 common intron variants. Variant effect predictor software indicated that the deep intronic variant at c.5220-8563A>G (intron 14) might act as a splicing acceptor. We developed iPSCs from patients and used genome editing to insert the elongation factor 1α promoter to express F8 messenger RNA (mRNA). Then, we confirmed the existence of abnormal F8 mRNA derived from aberrant splicing, resulting in a premature terminal codon as well as a significant reduction in F8 mRNA in iPSCs due to nonsense-mediated RNA decay. Gene repair by genome editing recovered whole F8 mRNA expression. Introduction of the intron variant into human B-domain–deleted F8 complementary DNA suppressed factor VIII (FVIII) activity and produced abnormal FVIII lacking the light chain in HEK293 cells. Furthermore, genome editing of the intron variant restored FVIII production. In summary, we have directly proven that the deep intronic variant in F8 results in aberrant splicing, leading to abnormal mRNA and nonsense-mediated RNA decay. Additionally, genome editing targeting the variant restored F8 mRNA and FVIII production. Our approach could be useful not only for identifying causal variants but also for verifying the therapeutic effect of personalized genome editing.
Evaluating the prevalence of inborn errors of immunity in adults with chronic immune thrombocytopenia or Evans syndrome
Authors: Jiang Debbie , Rosenlind Kira , Baxter Sarah , Gernsheimer Terry , Gulsuner Suleyman , Allenspach Eric J. , Keel Siobán B.
Published: October 2023

Inborn errors of immunity (IEIs) are monogenic disorders that predispose patients to immune dysregulation, autoimmunity, and infection. Autoimmune cytopenias, such as immune thrombocytopenia (ITP) and Evans syndrome (a combination of ITP and autoimmune hemolytic anemia), are increasingly recognized phenotypes of IEI. Although recent findings suggest that IEIs may commonly underlie pediatric ITP and Evans syndrome, its prevalence in adult patients with these disorders remains undefined. This study sought to estimate the prevalence of underlying IEIs among adults with persistent or chronic ITP or Evans syndrome using a next-generation sequencing panel encompassing >370 genes implicated in IEIs. Forty-four subjects were enrolled from an outpatient adult hematology clinic at a tertiary referral center in the United States, with a median age of 49 years (range, 20-83). Fourteen subjects (31.8%) had secondary ITP, including 8 (18.2%) with Evans syndrome. No cases of IEI were identified despite a high representation of subjects with a personal history of autoimmunity (45.5%) and early onset of disease (median age at diagnosis of 40 years [range, 2-77]), including 20.5% who were initially diagnosed as children. Eight subjects (18.2%) were found to be carriers of pathogenic IEI variants, which, in their heterozygous state, are not disease-causing. One case of TUBB1-related congenital thrombocytopenia was identified. Although systematic screening for IEI has been proposed for pediatric patients with Evans syndrome, findings from this real-world study suggest that inclusion of genetic testing for IEI in the routine work-up of adults with ITP and Evans syndrome has a low diagnostic yield.
Laboratory scale evaluation of the feasibility of locally found bladderworts as biological agents to control dengue vector, Aedes aegypti in Sri Lanka
Authors: Gunathilaka Nayana , Perera Ravina , Amerasinghe Deepika , Udayanga Lahiru
Published: October 2023

Background

The carnivorous genus Utricularia also includes aquatic species that have the potential to trap a wide range of prey, leading its death due to anoxia. However, the effectiveness of such an approach with carnivorous plants for vector control has not been evaluated in Sri Lanka.

Methods

Early instar (i & ii) and late instar (iii & iv) larvae of Aedes aegypti were exposed to locally found bladderwort (U. aurea Lour and Utricularia sp.). The experimental design was set with 10 larvae (both early and late instars separately) in 250 mL of water with bladderworts containing approximately 100 bladders in plant segments of both species, separately. Each treatment and control were repeated 50 times. The survival status of larvae was recorded daily until death or adult emergence. The larvae found whole or partially inside the bladders were attributed to direct predation. The Cox-regression model and Mantel-Cox log rank test were carried out to assess the survival probabilities of larvae in the presence of two bladderworts separately.

Results

The highest predation was observed when using early instar larvae in both U. aurea (97.8%) and Utricularia sp. (83.8%). The mortality caused due to predation by U. aurea was observed to be significantly higher according to the Mantel-Cox log-rank test (HR = 60.71, CI; 5.69–999.25, P = 0.004). The mortality rates of late instar stages of Ae. aegypti were observed to be lower in both U. aurea (82.6%) and Utricularia sp. (74.8%). Overall, the highest predation efficacy was detected from U. aurea (HR = 45.02; CI: 5.96–850.51, P = 0.017) even in late instar stages. The results suggested the cumulative predation in both plants on Ae. aegypti larvae was > 72%.

Conclusions

Utricularia aurea is a competent predator of Ae. aegypti larvae. Further, it is recommended to evaluate the feasibility of this plant to be used in the field as a control intervention in integrated vector management programmes.
Structural and functional implications of SLC13A3 and SLC9A6 mutations: an in silico approach to understanding intellectual disability
Authors: Hussain Syeda Iqra , Muhammad Nazif , Shah Salah Ud Din , Fardous Fardous , Khan Sher Alam , Khan Niamatullah , Rehman Adil U , Siddique Mehwish , Wasan Shoukat Ali , Niaz Rooh , Ullah Hafiz , Khan Niamat , Muhammad Noor , Mirza Muhammad Usman , Wasif Naveed , Khan Saadullah
Published: October 2023

Background

Intellectual disability (ID) is a condition that varies widely in both its clinical presentation and its genetic underpinnings. It significantly impacts patients’ learning capacities and lowers their IQ below 70. The solute carrier (SLC) family is the most abundant class of transmembrane transporters and is responsible for the translocation of various substances across cell membranes, including nutrients, ions, metabolites, and medicines. The SLC13A3 gene encodes a plasma membrane-localized Na+/dicarboxylate cotransporter 3 (NaDC3) primarily expressed in the kidney, astrocytes, and the choroid plexus. In addition to three Na + ions, it brings four to six carbon dicarboxylates into the cytosol. Recently, it was discovered that patients with acute reversible leukoencephalopathy and a-ketoglutarate accumulation (ARLIAK) carry pathogenic mutations in the SLC13A3 gene, and the X-linked neurodevelopmental condition Christianson Syndrome is caused by mutations in the SLC9A6 gene, which encodes the recycling endosomal alkali cation/proton exchanger NHE6, also called sodium-hydrogen exchanger-6. As a result, there are severe impairments in the patient’s mental capacity, physical skills, and adaptive behavior.

Methods and results

Two Pakistani families (A and B) with autosomal recessive and X-linked intellectual disorders were clinically evaluated, and two novel disease-causing variants in the SLC13A3 gene (NM 022829.5) and the SLC9A6 gene (NM 001042537.2) were identified using whole exome sequencing. Family-A segregated a novel homozygous missense variant (c.1478 C > T; p. Pro493Leu) in the exon-11 of the SLC13A3 gene. At the same time, family-B segregated a novel missense variant (c.1342G > A; p.Gly448Arg) in the exon-10 of the SLC9A6 gene. By integrating computational approaches, our findings provided insights into the molecular mechanisms underlying the development of ID in individuals with SLC13A3 and SLC9A6 mutations.

Conclusion

We have utilized in-silico tools in the current study to examine the deleterious effects of the identified variants, which carry the potential to understand the genotype-phenotype relationships in neurodevelopmental disorders.
Investigating associations between maternal stress, smoking and adverse birth outcomes: evidence from the All Our Families cohort
Authors: Yamamoto Shelby S. , Premji Shahirose S. , Saini Vineet , McDonald Sheila W. , Jhangri Gian S.
Published: October 2023

Background

Independently, active maternal and environmental tobacco smoke exposure and maternal stress have been linked to an increased risk of preterm birth and low birth weight. An understudied relationship is the potential for interactive effects between these risk factors.

Methods

Data was obtained from the All Our Families cohort, a study of 3,388 pregnant women < 25 weeks gestation recruited from those receiving prenatal care in Calgary, Canada between May 2008 and December 2010. We investigated the joint effects of active maternal smoking, total smoke exposure (active maternal smoking plus environmental tobacco smoke) and prenatal stress (Perceived Stress Scale, Spielberger State-Trait Anxiety Inventory), measured at two time points (< 25 weeks and 34–36 weeks gestation), on preterm birth and low birth weight.

Results

A marginally significant association was observed with the interaction active maternal smoking and Spielberger State-Trait Anxiety Inventory scores in relation to low birth weight, after imputation (aOR = 1.02, 95%CI: 1.00-1.03, p = 0.06). No significant joint effects of maternal stress and either active maternal smoking or total smoke exposure with preterm birth were observed. Active maternal smoking, total smoke exposure, Perceived Stress Scores, and Spielberger State-Trait Anxiety Inventory scores were independently associated with preterm birth and/or low birth weight.

Conclusions

Findings indicate the role of independent effects of smoking and stress in terms of preterm birth and low birthweight. However, the etiology of preterm birth and low birth weight is complex and multifactorial. Further investigations of potential interactive effects may be useful in helping to identify women experiencing vulnerability and inform the development of targeted interventions.
Predictive potential of optical coherence tomography parameters for the prognosis of decreased visual acuity after trabeculectomy in open-angle glaucoma patients with good vision
Authors: Takeda Yoko , Takahashi Naoki , Kiyota Naoki , Kokubun Taiki , Tsuda Satoru , Omodaka Kazuko , Yokoyama Yu , Nakazawa Toru
Published: October 2023

Background

Trabeculectomy (trab) is the most effective surgical procedure for lowering IOP and preventing glaucoma progression. However, decline in best-corrected visual acuity (BCVA) is one of the most serious postoperative complications of trab. Here, we investigated methods to predict decreased BCVA after trab in glaucoma patients with good preoperative BCVA.

Methods

This study included 35 eyes of 35 open-angle glaucoma (OAG) patients (male / female: 21 / 14, age: 64.0 ± 9.7 years old, preoperative intraocular pressure: 15.9 ± 5.4 mmHg, mean deviation: -18.1 ± 5.6 dB) with preoperative BCVA of 0.7 or better who underwent trab and were observed for more than 12 months. As a preoperative analysis, we measured temporal quadrant circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and ganglion cell complex thickness in a central strip between the disc and fovea (csGCCT), an area that corresponds to the location of the papillomacular bundle (PMB) in swept-source optical coherence tomography (OCT). We defined BCVA decline as a loss of more than 3 lines of BCVA after 12 months. Measurement parameters were compared between the BCVA-decline group and the non-BCVA-decline group.

Results

BCVA decline was detected in 11 cases (31.4%) 12 months after trab. There was a statistically significant difference in axial length (P = 0.049). A single logistic analysis showed that the BCVA-decline group had significantly lower cpRNFLT than the non-BCVA-decline group (27.7 ± 8.0 μm vs. 45.1 ± 5.3 μm, P < 0.001, cut-off value: 33.4 μm), as well as lower csGCCT (72.4 ± 7.7 μm vs. 87.5 ± 5.1 μm, P = 0.002, cut-off value: 82.3 μm). Multivariable logistic analysis showed that the BCVA-decline group had significantly lower temporal quadrant cpRNFLT (P < 0.001) and lower middle csGCCT (P < 0.001) compared to the non-BCVA-decline group.

Conclusions

Lower temporal quadrant cpRNFLT and middle csGCCT, OCT scan areas that correspond to the location of the PMB, might be biomarkers that predict BCVA decline after trab in OAG patients with good vision.
Effect of community based nutritional education on knowledge, attitude and compliance to IFA supplementation among pregnant women in rural areas of southwest Ethiopia: a quasi experimental study
Authors: Abdisa Diriba Kumara , Jaleta Debela Dereje , Tsegaye Dereje , Jarso Mohammedamin Hajure , Jaleta Gemechis Dereje , Tolesa Gamachis Firdisa , Kitila Keno Melkamu
Published: October 2023

Background

Compliance with the iron folic acid supplementation is low and not at the required level to prevent anaemia during pregnancy in many countries, including Ethiopia, even though an iron-folic acid supplementation program is being implemented. The aims of this study were to determine the effect of community-based nutritional education on knowledge, attitude, and compliance to IFA supplementation in Ilu Aba Bor zone of southwest Ethiopia.

Method

A pretest–posttest quasi-experimental study design consisting of intervention and control group was conducted among pregnant women. The total sample size of 472, therefore, 236 pregnant women for each interventional and control group from 16 kebeles were randomly selected in two districts. A multi-stage sampling technique was used to select the study participants. Then, individual study units were selected using a simple random sampling technique and followed until the end of the study period. Effect of community-based nutritional education on knowledge, attitude, and compliance to IFA supplementation among pregnant women in rural areas were measured.

Results

A total of 472 pregnant women participated in the study during the baseline and 437 (92.6%) were in the study until the end. The majority (49.2%) of respondents were 21–25 years of age, with a mean age of 23.4 (SD = 3.7) years. Community-based nutrition has resulted in a statistically significant increase in levels of maternal knowledge of IFAS by 15.2% in the intervention group compared to 5.1% in the control group. Similarly, the intervention group had odds of developing a positive attitude toward IFA 5.6 (4.01, 7.85) times higher than the control group. Moreover, in this study, the odds of compliance towards IFA supplementation were 3.9 (2.67, 5.57) times higher among those who received nutrition education than those women who did not.

Conclusion

This study revealed that community-based nutritional education can result in a significant change in knowledge, attitude, and compliance towards IFA supplementation and supports the literature suggesting the importance of the intervention to overcome the problem of poor compliance and its associated consequences.
Palliative care in Malawi: a scoping review
Authors: Palumbo Natalie , Tilly Alyssa , Namisango Eve , Ntizimira Christian , Thambo Lameck , Chikasema Maria , Rodin Gary
Published: October 2023

Background

Universal access to palliative care remains a distant goal in many low resource settings, despite the growing evidence of its benefits. The unmet need for palliative care is evident in Africa, but great strides in palliative care development have occurred in several African countries. Located in sub-Saharan Africa, Malawi has been regarded as an exemplar of progress in this area that is achievable in a low resource region. This scoping review examined the literature on the development and state of palliative care in Malawi according to the pillars of health care policy, medicine availability, education, implementation, research activity, and vitality of professionals and advocates.

Methods

A scoping review was conducted of the MEDLINE, Embase, Global Health, CINAHL, Web of Science and PsycINFO databases, as well as grey literature sources. Articles were included if they explored any aspect of palliative care in Malawi.

Results

114 articles were identified that met the inclusion criteria. This literature shows that Malawi has implemented diverse strategies across all pillars to develop palliative care. These strategies include creating a national stand-alone palliative care policy; integrating palliative care into the curricula of healthcare professionals and developing training for diverse service providers; establishing systems for the procurement and distribution of opioids; implementing diverse models of palliative care service delivery; and launching a national palliative care association. Malawi has also generated local evidence to inform palliative care, but several research gaps were identified.

Conclusions

Malawi has made considerable progress in palliative care development, although initiatives are needed to improve medicine availability, access in rural areas, and socioeconomic support for patients and their families living with advanced disease. Culturally sensitive research is needed regarding the quality of palliative care and the impact of therapeutic interventions.
Comparative analysis of serum and saliva samples using Raman spectroscopy: a high-throughput investigation in patients with polycystic ovary syndrome and periodontitis
Authors: Hu Dangli , Wang Jianmei , Cheng Tianfan , Li Huijun , Zhang Feng , Zhao Dan , Xu Xiaoyi , Yu Rong , Wen Ping , Cheng Yunfei , Xu Jian , Jin Lijian , Yao Jilong
Published: October 2023

Background

Polycystic ovary syndrome (PCOS) and periodontitis significantly affect women’s oral and systemic health worldwide, and yet increase the risk of cardiovascular-metabolic diseases like diabetes and coronary heart disease. Regarding the PCOS-periodontitis connection, whether sex hormones, metabolic and inflammatory mediators could account for the underlying linking mechanism needs to be further investigated. This case–control study evaluated the hormonal, metabolic and inflammatory profiles in PCOS and non-PCOS subjects with various periodontal conditions, via assessing serum and saliva samples by Raman spectroscopy.

Methods

A total of 66 females with PCOS and 22 systemically healthy female volunteers were recruited in a single hospital. Full-mouth periodontal examination was undertaken for identifying the subjects with periodontal health, gingivitis or periodontitis. The datasets of sex hormones and metabolic indicators were retrieved from the hospital information system. Both serum and saliva samples were collected for detecting inflammatory mediators and Raman spectroscopic assessment. The subjects were categorized into four groups according to their conditions of PCOS and periodontitis for Raman spectroscopic analysis. Partial least squares discriminant analysis was performed to examine the inter-group differences in Raman spectra.

Results

PCOS patients exhibited greater mean probing depth (P < 0.05) and higher serum levels of triglycerides (P < 0.05) and matrix metalloproteinase-8 (P < 0.05) than those in non-PCOS participants. Both probing depth and triglyceride level were positively correlated with PCOS (P < 0.05). There was a significant difference in mean Raman spectra of saliva samples among the four groups with different conditions of PCOS and periodontitis (P < 0.05), while no significant inter-group difference existed in serum samples.

Conclusions

The present study shows that periodontal condition may affect the biomolecular profiles of Raman spectra in serum and saliva of PCOS patients. It underscores the importance of the collaborative teamwork of dentists and gynecologists for enhancing women’s oral health, general wellbeing and quality of life.
Assessment of developmental rate of mouse embryos yielded from in vitro fertilization of the oocyte with treatment of melatonin and vitamin C simultaneously
Authors: Navid Shadan , Saadatian Zahra , Talebi Ali
Published: October 2023

Background

In recent decades, in vitro fertilization (IVF) has been widely used as a method of assisted reproductive technology (ART) to improve fertility in individuals. To be more successful in this laboratory method, we used the presence of two common types of antioxidants (melatonin and vitamin C) simultaneously and exclusively in IVF medium.

Methods

The cumulus-oocyte complexes (COCs) were obtained from Gonadotropin-releasing hormone (GnRH) and Human Chorionic Gonadotropin (HMG) -stimulated mice. Subsequently, metaphase II (MII) oocytes were fertilized in vitro. In the experiment, the IVF medium was randomly divided into two equal groups: The control group did not receive any antioxidants. In the treatment group, 100 µM melatonin and 5 mM vitamin C were added to the IVF medium. Finally, oocytes and putative embryos transferred into developmental medium and cultured 120 h after IVF to the blastocyst stage. After and before IVF, oocytes and putative embryos were stained with dichlorodihydrofluorescein diacetate (DCFDA) and the H2O2 level was measured with an inverted fluorescence microscope using ImageJ software. At the end of the fifth day after IVF, the expression of Bax and B cell lymphoma 2 (Bcl2) was evaluated using real-time PCR.

Results

The levels of reactive oxygen species (ROS) in oocytes and putative embryos observed in the treatment group demonstrated a significant reduce compared to the control group (p ≤ 0.01. (.Furthermore, the number of embryos in the blastocycte stage(P < 0.05), the expression level of the Bcl2 (P < 0.05) gene, the Bax unlike gene, significantly increased compared with the control group.

Conclusion

We conclude that the presence of melatonin and vitamin C antioxidants simultaneously and exclusively in the IVF medium leads to a reduction in ROS and ,as a result, improves the growth of the embryo up to the blastocyst stage.
Arts-based therapies, practices, and interventions in health
Authors: Van Lith Theresa , Ettenberger Mark
Published: October 2023

This collection focuses on creative art therapies, practices, and interventions in health contexts as part of the Mind-body interventions series of BMC Complementary Medicine and Therapies. The collection highlights the emerging value of the arts in complementary medicine and contributes to the expanding knowledge and integration of mind-body interventions and creative art practices.
Reasons for using traditional and complementary care by people living with HIV on antiretroviral therapy and association with interrupted care: a mixed methods study in Eswatini
Authors: Molemans Marjan , Reis Ria , Shabalala Fortunate , Dlamini Njabuliso , Masilela Nelisiwe , Simelane Njabulo , Pell Christopher , Chao Ariel , Spiegelman Donna , Vernooij Eva , van Leth Frank
Published: October 2023

The use of traditional, complementary, and alternative medicine (TCAM) can lead to delays and interruptions in the HIV continuum of care. This study explores reasons for TCAM use in people living with HIV on antiretroviral therapy (ART) in Eswatini and compares interrupted care between different types of TCAM users. Data were collected using surveys in the MaxART study (a test-and-treat trial) between 2014 and 2017 to assess the exposure, namely visiting a TCAM provider. Additionally, visit dates were retrieved from clinic records to assess the outcome, interrupted care. Open-ended questions were analysed with qualitative content analysis (n = 602) and closed questions with bivariable and multivariable analysis (n = 202). Out of 202 participants, 145 (72%) never used TCAM, 40 (20%) ever used, and 17 (8%) is currently using TCAM (diviners, herbalists, and religious healers). No differences in interrupted care were found comparing never (reference category), past (Odds Ratio: 1.31, 95% confidence interval: 0.63–2.72), and current users (1.34, 0.47–3.77), while adjusting for gender, time since HIV diagnosis, and time on ART. Contextual factors affecting the choice for TCAM were the influence of family, advice from the health facility, and religious beliefs. Individual factors include trust in biomedical care, type of illness, no need for additional care, and practical reasons such as financial means. In conclusion, individual and contextual factors influence the choice for TCAM. Interrupted care does not differ between never, past, and current users.
Bayesian belief network modelling approach for predicting and ranking risk factors for malaria infections among children under 5 years in refugee settlements in Uganda
Authors: Semakula Henry Musoke , Liang Song , Mukwaya Paul Isolo , Mugagga Frank , Nseka Denis , Wasswa Hannington , Mwendwa Patrick , Kayima Patrick , Achuu Simon Peter , Nakato Jovia
Published: October 2023

Background

Malaria risk factors at household level are known to be complex, uncertain, stochastic, nonlinear, and multidimensional. The interplay among these factors, makes targeted interventions, and resource allocation for malaria control challenging. However, few studies have demonstrated malaria’s transmission complexity, control, and integrated modelling, with no available evidence on Uganda’s refugee settlements. Using the 2018–2019 Uganda’s Malaria Indicator Survey (UMIS) data, an alternative Bayesian belief network (BBN) modelling approach was used to analyse, predict, rank and illustrate the conceptual reasoning, and complex causal relationships among the risk factors for malaria infections among children under-five in refugee settlements of Uganda.

Methods

In the UMIS, household level information was obtained using standardized questionnaires, and a total of 675 children under 5 years were tested for malaria. From the dataset, a casefile containing malaria test results, demographic, social-economic and environmental information was created. The casefile was divided into a training (80%, n = 540) and testing (20%, n = 135) datasets. The training dataset was used to develop the BBN model following well established guidelines. The testing dataset was used to evaluate model performance.

Results

Model accuracy was 91.11% with an area under the receiver-operating characteristic curve of 0.95. The model’s spherical payoff was 0.91, with the logarithmic, and quadratic losses of 0.36, and 0.16 respectively, indicating a strong predictive, and classification ability of the model. The probability of refugee children testing positive, and negative for malaria was 48.1% and 51.9% respectively. The top ranked malaria risk factors based on the sensitivity analysis included: (1) age of child; (2) roof materials (i.e., thatch roofs); (3) wall materials (i.e., poles with mud and thatch walls); (4) whether children sleep under insecticide-treated nets; 5) type of toilet facility used (i.e., no toilet facility, and pit latrines with slabs); (6) walk time distance to water sources (between 0 and 10 min); (7) drinking water sources (i.e., open water sources, and piped water on premises).

Conclusion

Ranking, rather than the statistical significance of the malaria risk factors, is crucial as an approach to applied research, as it helps stakeholders determine how to allocate resources for targeted malaria interventions within the constraints of limited funding in the refugee settlements.
Exosome-derived circ_0001785 delays atherogenesis through the ceRNA network mechanism of miR-513a-5p/TGFBR3
Authors: Tong Xiao , Dang Xuan , Liu Dongmei , Wang Ning , Li Miao , Han Jianbin , Zhao Jinjin , Wang Yueqing , Huang Meijiao , Yang Yanliang , Yang Yuhang , Wang Weili , Kou Yan , Kou Junjie
Published: October 2023

Purpose

Endothelial cell dysfunction is a major cause of early atherosclerosis. Although the role of extracellular vesicles in stabilizing atherosclerotic plaques is well established, the effect of circulating exosomes on plaque formation is still unknown. Here, we explored the effect of exosomes on atherosclerosis based on the function that exosomes can act on intercellular communication.

Patients and methods

We extracted serum exosomes from the blood of CHD patients (CHD-Exo) and healthy individuals (Con-Exo). The obtained exosomes were co-cultured with human umbilical vein endothelial cells (HUVECs) in vitro. In addition, we determined that circ_0001785 functions as a competing endogenous RNA (ceRNAs) in coronary artery disease by dual luciferase reporter gene analysis. The protective effect of circ_0001785 against endothelial cell injury was also verified using over-expression lentiviral transfection functional assays. In vivo experiments, we injected over-expressed circ_0001785 lentivirus into the tail vein of mice to observe its therapeutic effect on a mouse model of atherosclerosis.

Results

The vitro co-cultured results showed that the amount of plasma-derived exosomes have an increase in patients with coronary artery disease, and the inflammation and apoptosis of endothelial cells were exacerbated. Over-expression of circ_0001785 reduced endothelial cell injury through the ceRNA network pathway of miR-513a-5p/TGFBR3. Quantitative reverse transcription-polymerase chain reaction identified that the expressed amount of circ_0001785 was reduced in the circulating peripheral blood of CHD patients and increased within human and mouse atherosclerotic plaque tissue. The results of in vivo experiments showed that circ_0001785 reduced aortic endothelial cell injury and the formation of intraplaque neo-vascularization, and enhanced left ventricular diastolic function, thereby delaying the development of atherosclerosis in mice.

Conclusion

Our results demonstrated a new biomarker, exosome-derived circ_0001785, for atherogenesis, which can reduce endothelial cell injury and thus delay atherogenesis through the miR-513a-5p/TGFBR3 ceRNA network mechanism, providing an exosome-based intervention strategy for atherosclerosis.
Loss ratio of the capitation payment unit of the health-promoting entities in Colombia between 2017 and 2021: a financial–actuarial approach
Authors: Espinosa Oscar , Rodríguez Jhonathan , Urdinola B. Piedad , Do Nascimento Silva Pedro Luis , Sánchez Alejandra , Arias Martha-Liliana , Valdez Emiliano A. , Cheng Terence , Fisher Sara-Ellison
Published: October 2023

Background

Because of a change of government, the Colombian Ministry of Health and Social Protection is in the process of presenting a structural reform for the General System of Social Security in Health (GSSSH), in order to implement a ‘preventive and predictive health model’. However, it will always be relevant to review and analyze the fiscal implications of any proposed public policy program, to protect financial sustainability and to promote the better functioning of the system in question.

Methods

To contribute to this topic, we have calculated, using a financial–actuarial approach, the loss ratio for the years 2017 to 2021 for the Capitation Payment Unit (CPU) for all the Health-Promoting Entities (HPE) for both contributory and subsidized schemes. This information, derived from public reports available on the official website of the National Health Superintendency, allows us to estimate the financial burden of the institutions that guarantee access to and provision of health services and technologies in Colombia.

Results

The study shows that close to half of the HPEs in Colombia (which represent 11.6 million affiliates) have CPU loss ratios of more than 100% for the year 2021, evidencing insufficient resources for the operation of health insurance.

Conclusions

Finally, we propose some policy recommendations regarding the strengthening of informed decision-making to allow the healthy financial sustainability of the Colombian GSSSH.
Association of the presence of a COVID-19 infection at the time of birth and the rates of exclusive breastfeeding upon discharge in BFHI hospitals: a multicenter, prospective cohort study
Authors: Marín Gabriel Miguel Ángel , Martín Lozoya Sergio , de las Heras Ibarra Susana , Domingo Comeche Laura , González Carrasco Ersilia , Lalaguna Mallada Paula , Villó Sirerol Natalia , García Fernández Lucía , Jiménez Martínez José , Royuela Vicente Ana
Published: October 2023

Background

Very few studies have assessed the association between COVID-19 infection and the rates of exclusive breastfeeding (EBF) upon discharge following the first waves of the pandemic and after initiation of vaccination. The primary objective of this study is to compare the rates of EBF since birth upon discharge in mothers diagnosed with COVID-19 infection at the time of the delivery versus a group of non-infected mothers in maternity hospitals with Baby Friendly Hospital Initiative (BFHI) accreditation. The secondary objectives include determining the rates of any breastfeeding at three and six months of life in both groups, as well as determining the possible factors associated with EBF rates observed upon discharge.

Methods

An observational, Spanish multi-center hospital, prospective cohort study conducted from 1 to 2021 to 31 March 2022 and with follow-up during the first six months of life. Follow-up was performed via telephone contact with calls performed at three and six months. A multivariate logistic regression analysis model was used to identify the factors related to a lower probability of EBF upon discharge.

Results

308 mother-infant pairs participated in the study, 111 in the cohort of women with COVID infection and 197 in the comparison group. EBF upon discharge was 62.7% in the COVID group vs. 81.2% in the comparison group (p = 0.002); at three months; 52.4% vs. 57.0% (p = 0.33) were performing EBF, with the rates of EBF at six months being 43.0% vs. 39.3% (p = 0.45), respectively. Exposure to COVID-19 at delivery (AOR 5.28; 95% CI 2.01, 13.86), not practicing BF previously (AOR 36.3; 95% CI 7.02, 187.74), birth via Cesarean section (AOR 5.06; 95% CI 1.62, 15.79) and low birth weight of the newborn (AOR 1.01; 95% CI 1.01, 1.01) were associated with a greater risk of not performing EBF upon discharge.

Conclusions

Mothers with a mild or asymptomatic COVID-19 infection at the time of the delivery were less likely to have exclusively breastfed during their hospital stay than other mothers in these BFHI-accredited hospitals. However, there were no differences in breastfeeding rates between the groups at three and six months postpartum.
B-cells and regulatory T-cells in the microenvironment of HER2+ breast cancer are associated with decreased survival: a real-world analysis of women with HER2+ metastatic breast cancer
Authors: Steenbruggen Tessa G. , Wolf Denise M. , Campbell Michael J. , Sanders Joyce , Cornelissen Sten , Thijssen Bram , Salgado Roberto A. , Yau Christina , O-Grady Nick , Basu Amrita , Bhaskaran Rajith , Mittempergher Lorenza , Hirst Gillian L. , Coppe Jean-Philippe , Kok Marleen , Sonke Gabe S. , van ‘t Veer Laura J. , Horlings Hugo M.
Published: October 2023

Background

Despite major improvements in treatment of HER2-positive metastatic breast cancer (MBC), only few patients achieve complete remission and remain progression free for a prolonged time. The tumor immune microenvironment plays an important role in the response to treatment in HER2-positive breast cancer and could contain valuable prognostic information. Detailed information on the cancer-immune cell interactions in HER2-positive MBC is however still lacking. By characterizing the tumor immune microenvironment in patients with HER2-positive MBC, we aimed to get a better understanding why overall survival (OS) differs so widely and which alternative treatment approaches may improve outcome.

Methods

We included all patients with HER2-positive MBC who were treated with trastuzumab-based palliative therapy in the Netherlands Cancer Institute between 2000 and 2014 and for whom pre-treatment tissue from the primary tumor or from metastases was available. Infiltrating immune cells and their spatial relationships to one another and to tumor cells were characterized by immunohistochemistry and multiplex immunofluorescence. We also evaluated immune signatures and other key pathways using next-generation RNA-sequencing data. With nine years median follow-up from initial diagnosis of MBC, we investigated the association between tumor and immune characteristics and outcome.

Results

A total of 124 patients with 147 samples were included and evaluated. The different technologies showed high correlations between each other. T-cells were less prevalent in metastases compared to primary tumors, whereas B-cells and regulatory T-cells (Tregs) were comparable between primary tumors and metastases. Stromal tumor-infiltrating lymphocytes in general were not associated with OS. The infiltration of B-cells and Tregs in the primary tumor was associated with unfavorable OS. Four signatures classifying the extracellular matrix of primary tumors showed differential survival in the population as a whole.

Conclusions

In a real-world cohort of 124 patients with HER2-positive MBC, B-cells, and Tregs in primary tumors are associated with unfavorable survival. With this paper, we provide a comprehensive insight in the tumor immune microenvironment that could guide further research into development of novel immunomodulatory strategies.

Graphical Abstract
Development, validation and greenness assessment of a new electro-driven separation method for simultaneous analysis of cefixime trihydrate and linezolid in their fixed dose combination
Authors: Habeeb Maha R. , Morshedy Samir M. , Daabees Hoda G. , Elonsy Sohila M.
Published: October 2023

The establishment and validation of a straightforward, accurate, and eco-friendly capillary zone electrophoretic-diode array detection (CZE-DAD) procedure has been presented for concurrent measurement of two common antibiotics, namely, linezolid (LIN) and cefixime trihydrate (CEF), in their binary mixture or combined dosage form. The selected fused silica capillary has total and effective lengths equal to 58.5 cm and 50 cm, respectively, with a 50 µm internal diameter. Injections were performed utilizing 100 mM borate buffer at pH 10.2 as the background electrolyte (BGE) with a 15.0 s injection time. The finally utilized voltage was 30 kV. DAD was programmed to measure LIN at 250 nm and CEF at 285 nm. In less than 6 min, the two cited drugs were resolved at 2.51 and 5.47 min for LIN and CEF respectively. The introduced procedure had a linear response in the concentration range of 5–50 μg/mL for both analytes with correlation coefficients > 0.9999. Detection and quantification limits were 1.213 and 4.042 μg/mL, respectively, for LIN and 0.301 and 1.004 μg/mL, respectively, for CEF. Validation was conducted according to the International Council for Harmonization (ICH), concerning linearity, detection and quantitation limits, range, accuracy, precision, selectivity, and robustness. Precision was found acceptable due to the low relative standard deviation (RSD%) values that did not exceed 1.86% either for repeatability or for intermediate precision. Additionally, the adequately recovered concentrations and the low values of percentage relative error (Er%) provide evidence of the accuracy of the proposed method. On the other hand, the robustness of the introduced method was affirmed by the acceptable RSD% values that did not exceed 0.6% after deliberate changes in the following procedure parameters: buffer concentration, buffer pH, and wavelength. Finally, the ability of the presented method to quantify the two tested drugs in laboratory-prepared tablets was confirmed by the adequate recoveries (≥ 99%) utilizing the standard-addition procedure, along with the absence of any significant difference between the proposed method and the reference method as proven by the student’s t-test and the variance-ratio F-test values that did not exceed the theoretical ones. The analytical Eco-Scale and the analytical GREEness metric (AGREE) were the tools utilized for greenness assessment. This CZE procedure is the first electro-driven separation method that was utilized for the analysis of both antibiotics in their combined laboratory-prepared tablets with no interference from the co-formulated adjuvants.