bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative serum selenium predicts acute kidney injury after adult cardiac surgery
Authors: Fu Guowei , Bai Shuying
Published: March 2024

Background

The relationship between serum selenium (Se) and acute kidney injury after adult cardiac surgery (CSA-AKI) remains controversial. This study aimed to investigate the association of preoperative Se level with incident CSA-AKI.

Method and Results

A retrospective cohort study was conducted on patients who underwent cardiac surgery. The primary outcome was incident CSA-AKI. Multivariable logistic regression models and natural cubic splines were used to estimate the association of Se levels and primary outcome. A total of 453 patient with a mean age of 62.97 years were included. Among all patients, 159 (35.1%) incident cases of CSA-AKI were identified. The level of preoperative Se concentration in patients with CSA-AKI was significant lower than that in patients without CSA-AKI. The higher preoperative Se level was significantly associated with decreased risk of CSA-AKI (adjusted OR 0.91, 95% CI: 0.87–0.99). Dose-response relationship curve revealed a nearly L-shape correlation between serum Se selenium levels and incident CSA-AKI.

Conclusion

Our study suggested that a higher level of serum Se was significantly associated with lower risk of CSA-AKI. Further prospective studies are needed to clarify the causal relationship between serum Se level and incident CSA-AKI.
A qualitative examination of primary care team’s participation in the distribution of the COVID-19 vaccination
Authors: Ashcroft Rachelle , Donnelly Catherine , Lam Simon , Sheffield Peter , Hamilton Bryn , Kemp Connor , Adamson Keith , Brown Judith Belle
Published: March 2024

Background

Primary health care (PHC) has historically led and implemented successful immunization programs, driven by strong relationships with patients and communities. During the COVID-19 pandemic, Canada began its vaccination strategy with mass immunizations that later included local efforts with PHC providers. This study seeks to understand how PHC contributed to the different phases of the COVID-19 vaccination rollouts in Ontario, Canada’s most populous province.

Methods

We conducted a descriptive qualitative study with focus groups consisting of PHC providers, administrators, and staff in Ontario. Eight focus groups were held with 39 participants representing geographic diversity across the six Ontario Health regions. Participants reflected a diverse range of clinical, administrative, and leadership roles. Each focus group was audio-recorded and transcribed with transcriptions analyzed using thematic analysis.

Results

With respect to understanding PHC teams’ participation in the different phases of the COVID-19 vaccination rollouts, we identified five themes: (i) supporting long-term care, (ii) providing leadership in mass vaccinations, (iii) integrating vaccinations in PHC practice sites, (iv) reaching those in need through outreach activities; and (v) PHC’s contributions being under-recognized.

Conclusions

PHC was instrumental in supporting COVID-19 vaccinations in Ontario, Canada across all phases of the rollout. The flexibility and adaptability of PHC allowed teams to participate in both large-scale and small-scale vaccination efforts.
Circulatory resistin levels in inflammatory bowel disease: a systematic review and meta-analysis
Authors: Behnoush Amir Hossein , Maroufi Seyede Parmis , Reshadmanesh Tara , Mohtasham Kia Yasmin , Norouzi Mitra , Mohammadi Seyedeh Mina , Klisic Aleksandra , Khalaji Amirmohammad
Published: March 2024

Background

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic relapsing-remitting systemic disease of the gastrointestinal tract with rising incidence. Studies have shown that adipocytes play a crucial role in patients with IBD by actively participating in systemic immune responses. The present study was designed to investigate the correlation between the circulatory levels of resistin, as an adipokine, and active and remission phases of IBD in comparison with healthy controls.

Methods

Relevant articles were retrieved from PubMed, Embase, the Web of Science, and Scopus from inception until June 2023. Estimation of the standardized mean difference (SMD) and 95% confidence interval (CI) for comparison of plasma/serum resistin levels between IBD patients, patients in remission, and healthy controls were conducted through random-effect meta-analysis.

Results

A total of 19 studies were included, assessing 1836 cases. Meta-analysis indicated that generally, serum/plasma resistin levels were higher in IBD patients in comparison with healthy controls (SMD 1.33, 95% CI 0.58 to 2.08, p-value < 0.01). This was true for each of the UC and CD separate analyses, as well. Moreover, it was shown that higher serum/plasma resistin levels were detected in the active phase of IBD than in the remission phase (SMD 1.04, 95% CI 0.65 to 1.42, p-value = 0.01). Finally, higher serum/plasma resistin levels were found in the remission phase compared to healthy controls (SMD 0.60, 95% CI 0.15 to 1.06, p-value < 0.01).

Conclusion

The results of this systematic review and meta-analysis support the conclusion that circulating resistin levels are increased in IBD (both UC and CD). Also, higher resistin levels were recorded in the remission phase of IBD in comparison with healthy controls. This indicates that further studies may provide valuable insights into the role of resistin in the pathogenesis of IBD.
Clinical decision support system supported interventions in hospitalized older patients: a matter of natural course and adequate timing
Authors: Zwietering NA , Linkens AEMJH , Kurstjens D , van der Kuy PHM , van Nie-Visser N , van de Loo BPA , Hurkens KPGM , Spaetgens B
Published: March 2024

Background

Drug-related problems (DRPs) and potentially inappropriate prescribing (PIP) are associated with adverse patient and health care outcomes. In the setting of hospitalized older patients, Clinical Decision Support Systems (CDSSs) could reduce PIP and therefore improve clinical outcomes. However, prior research showed a low proportion of adherence to CDSS recommendations by clinicians with possible explanatory factors such as little clinical relevance and alert fatigue.

Objective

To investigate the use of a CDSS in a real-life setting of hospitalized older patients. We aim to (I) report the natural course and interventions based on the top 20 rule alerts (the 20 most frequently generated alerts per clinical rule) of generated red CDSS alerts (those requiring action) over time from day 1 to 7 of hospitalization; and (II) to explore whether an optimal timing can be defined (in terms of day per rule).

Methods

All hospitalized patients aged ≥ 60 years, admitted to Zuyderland Medical Centre (the Netherlands) were included. The evaluation of the CDSS was investigated using a database used for standard care. Our CDSS was run daily and was evaluated on day 1 to 7 of hospitalization. We collected demographic and clinical data, and moreover the total number of CDSS alerts; the total number of top 20 rule alerts; those that resulted in an action by the pharmacist and the course of outcome of the alerts on days 1 to 7 of hospitalization.

Results

In total 3574 unique hospitalized patients, mean age 76.7 (SD 8.3) years and 53% female, were included. From these patients, in total 8073 alerts were generated; with the top 20 of rule alerts we covered roughly 90% of the total. For most rules in the top 20 the highest percentage of resolved alerts lies somewhere between day 4 and 5 of hospitalization, after which there is equalization or a decrease. Although for some rules, there is a gradual increase in resolved alerts until day 7. The level of resolved rule alerts varied between the different clinical rules; varying from > 50–70% (potassium levels, anticoagulation, renal function) to less than 25%.

Conclusion

This study reports the course of the 20 most frequently generated alerts of a CDSS in a setting of hospitalized older patients. We have shown that for most rules, irrespective of an intervention by the pharmacist, the highest percentage of resolved rules is between day 4 and 5 of hospitalization. The difference in level of resolved alerts between the different rules, could point to more or less clinical relevance and advocates further research to explore ways of optimizing CDSSs by adjustment in timing and number of alerts to prevent alert fatigue.
Isolation and characterization of lytic bacteriophages from various sources in Addis Ababa against antimicrobial-resistant diarrheagenic Escherichia coli strains and evaluation of their therapeutic potential
Authors: Sada Tamirat Salile , Tessema Tesfaye Sisay
Published: March 2024

Background

Escherichia coli is a common fecal coliform, facultative aerobic, gram-negative bacterium. Pathogenic strains of such microbes have evolved to cause diarrhea, urinary tract infections, and septicemias. The emergence of antibiotic resistance urged the identification of an alternative strategy. The use of lytic bacteriophages against the control of pathogenic E. coli in clinics and different environmental setups (waste and drink water management) has become an alternative therapy to antibiotic therapy. Thus, this study aimed to isolate and characterize lytic bacteriophage from various sources in Addis Ababa, tested them against antimicrobial-resistant diarrheagenic E. coli strains and evaluated their therapeutic potential under in vitro conditions.

Methods

A total of 14 samples were processed against six different diarrheagenic E. coli strains. The conventional culture and plaque analysis agar overlay method was used to recover lytic bacteriophage isolates. The phage isolates were characterized to determine their lytic effect, growth characteristics, host range activity, and stability under different temperature and pH conditions. Phage isolates were identified by scanning electron microscope (SEM), and molecular techniques (PCR).

Results

In total, 17 phages were recovered from 84 tested plates. Of the 17 phage isolates, 11 (65%) were Myoviridae-like phages, and 6 (35%) phage isolates were Podoviridae and Siphoviridae by morphology and PCR identification. Based on the host range test, growth characteristics, and stability test 7 potent phages were selected. These phages demonstrated better growth characteristics, including short latent periods, highest burst sizes, and wider host ranges, as well as thermal stability and the ability to survive in a wide range of pH levels.

Conclusions

The promising effect of the phages isolated in this study against AMR pathogenic E. coli has raised the possibility of their use in the future treatment of E. coli infections.
Placental pathology and neonatal morbidity: exploring the impact of gestational age at birth
Authors: Budal Elisabeth B. , Kessler Jørg , Eide Geir Egil , Ebbing Cathrine , Collett Karin
Published: March 2024

Aim

To evaluate placental pathology in term and post-term births, investigate differences in clinical characteristics, and assess the risk of adverse neonatal outcome.

Methods

This prospective observational study included 315 singleton births with gestational age (GA) > 36 weeks + 6 days meeting the local criteria for referral to placental histopathologic examination. We applied the Amsterdam criteria to classify the placentas. Births were categorized according to GA; early-term (37 weeks + 0 days to 38 weeks + 6 days), term (39 weeks + 0 days to 40 weeks + 6 days), late-term (41 weeks + 0 days to 41 weeks + 6 days), and post-term births (≥ 42 weeks + 0 days). The groups were compared regarding placental pathology findings and clinical characteristics. Adverse neonatal outcomes were defined as 5-minute Apgar score < 7, umbilical cord artery pH < 7.0, admission to the neonatal intensive care unit or intrauterine death. A composite adverse outcome included one or more adverse outcomes. The associations between placental pathology, adverse neonatal outcomes, maternal and pregnancy characteristics were evaluated by logistic regression analysis.

Results

Late-term and post-term births exhibited significantly higher rates of histologic chorioamnionitis (HCA), fetal inflammatory response, clinical chorioamnionitis (CCA) and transfer to neonatal intensive care unit (NICU) compared to early-term and term births. HCA and maternal smoking in pregnancy were associated with adverse outcomes in an adjusted analysis. Nulliparity, CCA, emergency section and increasing GA were all significantly associated with HCA.

Conclusions

HCA was more prevalent in late and post-term births and was the only factor, along with maternal smoking, that was associated with adverse neonatal outcomes. Since nulliparity, CCA and GA beyond term are associated with HCA, this should alert the clinician and elicit continuous intrapartum monitoring for timely intervention.
The association between smoking and family health with the mediation role of personality among Chinese people: nationwide cross-sectional study
Authors: Chen Jiangyun , Luo Menglin , Gan Li , Li Haomiao , Liu Siyuan , Ren Na , Zhou Yan , Yang Jiao , Zhou Haozheng , Yin Xuanhao , Wan Jiahuan , Yang Xinlei , Wu Yibo , Luo Zenni
Published: March 2024

Background

There may be unexplored interactions between family health, personality, and smoking that could help provide new perspectives on tobacco control.

Objective

To examine the relationship between the health of one’s family and their smoking habits, as well as investigate the potential influence of personality on this relationship.

Methods

For this cross-sectional investigation, a national survey conducted in China in 2022 recruited a total of 21,916 individuals. The Family Health Scale was utilized to assess the health of the family. The 10-item Big Five Inventory scale was utilized to assess the Big five personality traits. The relationship between big five personality, family health, and smoking were investigated using binary and linear logistic regression. The indirect effects mediated by Big five personality were analyzed using mediation analysis with Sobel tests, and the indirect effects were composited using the Karlson-Holm-Breen method.

Results

The overall prevalence of smoking in the study population was 14.87%, 26.19% for males and 3.54% for females. Urban and rural smoking prevalence was 13.81% and 16.10% respectively. Binary logistic regression analysis revealed a significant negative relationship between smoking and family health (odds ratio 0.964, 95% CI 0.959, 0.970, P < 0.001) with covariates controlled. The Karlson-Holm-Breen composition facilitated the connection between extraversion (47.81%) and nervousness (52.19%).

Conclusions

Preventive interventions for smoking behavior should prioritize family health and the Big five personality as significant areas to focus on. According to this study, in addition to implementing various interventions for different personalities, family health should be strengthened to reduce smoking behavior.
Financial burden faced by breastfeeding mothers caring for children diagnosed with cancer in Ghana; an exploratory qualitative study
Authors: Marfo Margaret , Acheampong Angela Kwartemaa , Asare Comfort
Published: March 2024

Background

When children are diagnosed of cancer, parents face varied financial issues. Among some of the identifiable factors that cause financial challenges among breastfeeding mothers include the high cost of childhood cancer care. The high cost of childhood cancer care could impede the sustainability of access to prompt care. There is paucity of literature on the financial burdens faced by breastfeeding mothers with children diagnosed with cancer in Ghana. Therefore, this study sought to explore the financial burden faced by mothers with breastfeeding children diagnosed with cancer.

Methods

The study employed qualitative exploratory descriptive design. One-on-one interviews were conducted among 13 mothers with breastfeeding children diagnosed of cancer. Permission was sought for data to be recorded, transcribed concurrently and inductive content analysis done.

Results

Three main themes emerged after data analysis: High cost (sub-themes; expensive medications, laboratory investigation fees, and cost of mothers’ feeding), Public support (sub-themes; appeal for funds, national health insurance scheme) and Self-financing (loans, personal savings). Most of the breastfeeding mothers narrated that high cost of childhood cancer care generated financial distress to them. They shared that the cost involved in purchasing their children’s cancer medications, paying for laboratory investigations and feeding themselves to produce adequate breastmilk to feed their children were challenging. Some of the mothers self-financed the cost of their children’s cancer care through loans and personal savings.

Conclusion

Government and other stakeholders should allocate annual budget and funds towards childhood cancer care to lessen the financial burden breastfeeding mothers caring for children with cancer experience.
Phytoconstituent analysis, anti-inflammatory, antimicrobial and anticancer effects of nano encapsulated Convolvulus arvensis L. extracts
Authors: Osman Ezzat E. A. , Shemis Mohamed A. , Abdel-Hameed El-Sayed S. , Gouda Abdullah E. , Hassan Hanem , Atef Nahla , Mamdouh Samah
Published: March 2024

Background

The Convolvulus genus is distributed all over the world and has a long history in traditional medicine. As nanotechnology expands its reach into areas like drug delivery and biomedicine, this study intends to assess the potential of Convolvulus arvensis L. extracts as anti-bacterial, anti-inflammatory and anti-cancer agents, along with chemical profiling of the methanolic (MeOH) extract active ingredients.

Methods

The chemical composition of an 85% MeOH extract was investigated by liquid chromatography with an electrospray source connected to mass spectrometry (LC-ESI-MS). Both the 85% MeOH extract and n-butanol fraction of C. arvensis were loaded for the first time on alginate/chitosan nanoparticles. The 85% MeOH extract, n-butanol fraction and their loaded nanoparticles were tested for their cytotoxicity, anticancer, anti-inflammatory and antibacterial activity (against pathogenic bacteria, E. coli and S. aureus).

Results

The chemical investigation of 85% MeOH extract of C. arvensis underwent LC-ESI-MS analysis, revealing twenty-six phenolic substances, of which 16 were phenolic acids, 6 were flavonoids, 1 glycolipid, 1 sesquiterpene and 2 unknown compounds. The FT-IR spectra confirmed the encapsulation of the 85% MeOH extract and n-butanol fraction onto alginate/chitosan nanoparticles and small size obtained by TEM maintained them nontoxic and enhanced their anti-inflammatory activity (the IC50 was decreased from 1050 to 175 µg/ml). The anti-cancer activity against HepG2 was increased and the cell viability was decreased from 28.59 ± 0.52 to 20.80 ± 0.27 at a maximum concentration of 1000 µg/ml. In addition, the MIC of encapsulated extracts was decreased from 31.25 to7.78 µg/ml in E. coli (Gm-ve) and from 15.56 to 7.78 µg/ml in S. aureus (Gm + ve) bacteria.

Conclusion

Both alginate and chitosan are excellent natural polymers for the encapsulation process, which affects positively on the bioactive constituents of C. arvensis extracts and improves their biological properties.
‘First, do no harm’: systematic program evaluation of an equine veterinary service-learning initiative with Indigenous communities in Canada
Authors: Tan Jean-Yin , Poitras Pratt Yvonne , Danyluk Patricia
Published: March 2024

Background

Veterinary students have historically lacked meaningful experiential learning opportunities in equine medicine. At the same time, there are barriers to accessing veterinary care in Indigenous communities stemming from colonial injustices. In 2018–2019, a partnership was initiated where University of Calgary students began to provide equine veterinary services to Indigenous communities. As the first-documented equine veterinary service-learning initiative in Indigenous communities embedded in a veterinary curriculum, the purpose of the study is to systematically evaluate the program for its potential impact as part of a formative process for improvement.

Methods

Multiple parties in the program were engaged in a convergent, parallel, mixed-methods systematic program evaluation to explore the main program outcomes: (1) equine veterinary care; (2) clinical experiential student education; (3) cultural training of veterinary professionals and students; and (4) education of community members. The hypothesis was that ethical development using the “first, do no harm principle” would lead to benefits including a healthy horse population, a technically and culturally competent veterinary community, and an educated horse clientele.

Results

The program had a positive impact on accessibility to veterinary care and self-reported improvement in veterinary and cultural competency. In addition to the hypothesized program outcomes, additional program outcomes and effects were identified, including reciprocal learning and relationship building with the Indigenous community, leading to trust and equity-building. The students learned from both the in-community programming as well as the Indigenous community members they worked with.

Conclusion

Program evaluation of an equine service-learning initiative in Indigenous communities reveals multiple and profound impacts including improved patient health status, wider scope of veterinary and cultural learning, strengthened relationships, and reciprocal learning with partnering Indigenous communities.
SurvInt: a simple tool to obtain precise parametric survival extrapolations
Authors: Gallacher Daniel
Published: March 2024

Background

Economic evaluation of emerging health technologies is mandated by agencies such as the National Institute for Health and Care Excellence (NICE) to ensure their cost is proportional to their benefit. To avoid bias, NICE stipulate that the benefit of a treatment is assessed across the lifetime of the patient population, which can be many decades. Unfortunately, follow-up from a clinical trial will not usually cover the required period and the observed follow-up will require extrapolation. For survival data this is often done by selecting a preferred model from a set of candidate parametric models. This approach is limited in that the choice of model is restricted to those originally fitted. What if none of the models are consistent with clinical prediction or external data?

Method/Results

This paper introduces SurvInt, a tool that estimates the parameters of common parametric survival models which interpolate key survival time co-ordinates specified by the user, which could come from external trials, real world data or expert clinical opinion. This is achieved by solving simultaneous equations based on the survival functions of the parametric models. The application of SurvInt is shown through two examples where traditional parametric modelling did not produce models that were consistent with external data or clinical opinion. Additional features include model averaging, mixture cure models, background mortality, piecewise modelling, restricted mean survival time estimation and probabilistic sensitivity analysis.

Conclusions

SurvInt allows precise parametric survival models to be estimated and carried forward into economic models. It provides access to extrapolations that are consistent with multiple data sources such as observed data and clinical predictions, opening the door to precise exploration of regions of uncertainty/disagreement. SurvInt could avoid the need for post-hoc adjustments for complications such as treatment switching, which are often applied to obtain a plausible survival model but at the cost of introducing additional uncertainty. Phase III clinical trials are not designed with extrapolation in mind, and so it is sensible to consider alternative approaches to predict future survival that incorporate external information.
The biosafety incident response competence scale for clinical nursing staff: a development and validation study
Authors: Wu Chao , Zhang Hongli , Zhang Yinjuan , Hu Mengyi , Lin Yawei , He Jing , Li Shuwen , Zhang Yulian , Lang Hong-juan
Published: March 2024

Aims

This study was designed to develop a biosafety incident response competence scale and evaluate its validity and reliability among clinical nurses.

Design

This study employed a sequential approach, comprising four phases: (1) the establishment of a multidimensional conceptual model, (2) the preliminary selection of the items, (3) further exploration and psychometric testing of the items, (4) the application of the scale among clinical nurses.

Methods

The biosafety incident response competence conceptual model was developed through literature review and the Delphi method. A total of 1,712 clinical nurses participated in the preliminary items selection, while 1,027 clinical nurses were involved in the further psychometric testing from July 2023 to August 2023. The item analysis, exploratory factor analysis and confirmatory factor analysis were conducted to evaluate the construct validity. Reliability was measured using Cronbach’s alpha, split-half reliability, and test-retest reliability, while validity analysis included content validity, structural validity, convergent validity, and discriminant validity. From September to November 2023, we conducted a survey using the established scale with a total of 4338 valid questionnaires collected. T-test and variance analysis was employed to determine potential variations in biosafety incident response competence based on participants characteristics.

Results

The final scale is composed of 4 factors and 29 items, including monitoring and warning abilities, nursing disposal abilities, biosafety knowledge preparedness, and infection protection abilities. The explanatory variance of the 4 factors was 75.100%. The Cronbach’s alpha, split-half reliability and test-retest reliability were 0.974, 0.945 and 0.840 respectively. The Scale-level content validity index was 0.866. The Average Variance Extracted of the 4 factors was larger than 0.5, the Construct Reliability was larger than 0.7, and the Heterotrait-Monotrait ratio were less than 0.9. There were significant differences in the scores of response competence among nurses of different ages, working years, titles, positions, departments, marital status and participation in biosafety training (all P < 0.05).

Conclusions

The biosafety incident response competence scale for nurses exhibits satisfactory reliability and validity, making it a valuable tool for assessing clinical nurses’ abilities in responding to biosafety incidents.
Access to child developmental assessment services in culturally and linguistically diverse metropolitan Sydney: a retrospective cohort analysis
Authors: Bentley Sibella E. , Garg Pankaj , Gudes Ori , Hurwitz Romy , Vivekanandarajah Sinthu , So Lydia Y.L.
Published: March 2024

Background

Despite the increasing prevalence of neurodevelopmental disorders (NDD), data regarding access to child development services have remained limited globally. Long wait times are a major barrier to developmental assessments, impacting on care and outcomes. The aim is to retrospectively analyse the demographic profile and prioritisation of patients seen at a child developmental assessment service (CDAS) in a vulnerable region of Sydney, and explore factors affecting wait times.

Methods

Data was collated and analysed for 2354 patients from 2018 to 2022. Socio-Economic Indexes for Areas (SEIFA) were collated from the Australian Bureau of Statistics. Descriptive statistics were used for demographic data and various statistical methods were used to analyse the relationships and impact of factors likely to affect wait lists.

Results

The median age was 51 months (IQR41-61) and males comprised 73.7% of the cohort. 64% of children were from culturally and linguistically diverse backgrounds (CALD) and 47% lived in the most disadvantaged suburbs. The median wait time was 302.5 days (IQR175-379) and 70% of children were seen within 12 months. CALD patients and children over 5-years had shorter wait times. Most children with Global Developmental Delay (GDD) were from the lowest four SEIFA deciles and waited longer for an appointment. 42.6% were seen within the priority allocated time or sooner. Children with ASD and/or severe GDD were prioritised to be seen earlier. Overall, the study could not demonstrate any difference in the wait times according to the prioritisation groups.

Conclusion

This study provides insights into the profile, prioritisation processes and wait lists of children seen by CDAS in South Western Sydney with high rates of social vulnerability and presents an argument to discuss benchmarking targets with service providers. It identifies the need to prioritise children living in suburbs with socioeconomic disadvantage and refine prioritisation and data collection processes to improve wait times.
Efficacy and safety of Infliximab in systemic sarcoidosis according to GenPhenReSa organ-involvement phenotype: a retrospective study of 55 patients
Authors: Rivière Etienne , Jourde Wendy , Gensous Noémie , Demant Xavier , Ribeiro Emmanuel , Duffau Pierre , Mercié Patrick , Viallard Jean-François , Lazaro Estibaliz
Published: March 2024

Background

Infliximab is currently recommended as a third-line treatment for refractory sarcoidosis. Data in function of clinical phenotype are currently lacking. We evaluated patients’ characteristics and responses to infliximab according to their GenPhenReSa cluster.

Methods

We evaluated clinical and biological characteristics of patients diagnosed with sarcoidosis who received infliximab between September 2008 and April 2019 at our centre.

Results

Fifty-five patients (median disease duration, 87 months) received infliximab: 48 (87%) as a second- or third-line treatment, and 7 (13%) as a first-line treatment. After a median duration of 12 months, 24 (45%) and 14 (25%) patients achieved complete and partial responses, respectively, together with a significant decrease in the number of affected organs and tapering of steroid doses. All patients with neurosarcoidosis (OR 17), 90% in group 2 (ocular-cardiac-cutaneous-CNS, OR 7.4), and approximately two-thirds of those in groups 1 (abdominal organs), 4 (pulmonary-lympho-nodal), and 5 (extrapulmonary), achieved a response, whereas patients in group 3 (musculoskeletal-cutaneous) had a treatment-failure OR of 9. Infliximab could be stopped after complete remission was achieved in 7 patients: 4 relapsed after a median of 6 months. Overall, 36% of patients experienced serious adverse events, mainly infections, which led to treatment cessation in 29% of patients and caused two deaths.

Conclusions

Other than patients with musculoskeletal-cutaneous involvement (group 3), infliximab led to a good response for patients with CNS (group 2) and liver (group 1) organ-predominant sarcoidosis. However, it led to serious infections and merely suspended sarcoidosis, so further research on factors predictive of relapse is needed.
The strain-dependent cytostatic activity of Lactococcus lactis on CRC cell lines is mediated through the release of arginine deiminase
Authors: Jastrząb Rafał , Tomecki Rafał , Jurkiewicz Aneta , Graczyk Damian , Szczepankowska Agnieszka K. , Mytych Jennifer , Wolman Damian , Siedlecki Pawel
Published: March 2024

Background

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, posing a serious public health challenge that necessitates the development of new therapeutics, therapies, and prevention methods. Among the various therapeutic approaches, interventions involving lactic acid bacteria (LAB) as probiotics and postbiotics have emerged as promising candidates for treating and preventing CRC. While human-isolated LAB strains are considered highly favorable, those sourced from environmental reservoirs such as dairy and fermented foods are also being recognized as potential sources for future therapeutics.

Results

In this study, we present a novel and therapeutically promising strain, Lactococcus lactis ssp. lactis Lc4, isolated from dairy sources. Lc4 demonstrated the ability to release the cytostatic agent - arginine deiminase (ADI) - into the post-cultivation supernatant when cultured under conditions mimicking the human gut environment. Released arginine deiminase was able to significantly reduce the growth of HT-29 and HCT116 cells due to the depletion of arginine, which led to decreased levels of c-Myc, reduced phosphorylation of p70-S6 kinase, and cell cycle arrest. The ADI release and cytostatic properties were strain-dependent, as was evident from comparison to other L. lactis ssp. lactis strains.

Conclusion

For the first time, we unveil the anti-proliferative properties of the L. lactis cell-free supernatant (CFS), which are independent of bacteriocins or other small molecules. We demonstrate that ADI, derived from a dairy-Generally Recognized As Safe (GRAS) strain of L. lactis, exhibits anti-proliferative activity on cell lines with different levels of argininosuccinate synthetase 1 (ASS1) expression. A unique feature of the Lc4 strain is also its capability to release ADI into the extracellular space. Taken together, we showcase L. lactis ADI and the Lc4 strain as promising, potential therapeutic agents with broad applicability.
Early childhood exposure to environmental phenols and parabens, phthalates, organophosphate pesticides, and trace elements in association with attention deficit hyperactivity disorder (ADHD) symptoms in the CHARGE study
Authors: Oh Jiwon , Kim Kyoungmi , Kannan Kurunthachalam , Parsons Patrick J. , Mlodnicka Agnieszka , Schmidt Rebecca J. , Schweitzer Julie B. , Hertz-Picciotto Irva , Bennett Deborah H.
Published: March 2024

Background

A growing body of literature investigated childhood exposure to environmental chemicals in association with attention-deficit/hyperactivity disorder (ADHD) symptoms, but limited studies considered urinary mixtures of multiple chemical classes. This study examined associations of concurrent exposure to non-persistent chemicals with ADHD symptoms in children diagnosed with autism spectrum disorder (ASD), developmental delay (DD), and typical development (TD).

Methods

A total of 549 children aged 2–5 years from the Childhood Autism Risks from Genetics and Environment (CHARGE) case-control study were administered the Aberrant Behavior Checklist (ABC). This study focused on the ADHD/noncompliance subscale and its two subdomains (hyperactivity/impulsivity, inattention). Sixty-two chemicals from four classes (phenols/parabens, phthalates, organophosphate pesticides, trace elements) were quantified in child urine samples, and 43 chemicals detected in > 70% samples were used to investigate their associations with ADHD symptoms. Negative binomial regression was used for single-chemical analysis, and weighted quantile sum regression with repeated holdout validation was applied for mixture analysis for each chemical class and all chemicals. The mixture analyses were further stratified by diagnostic group.

Results

A phthalate metabolite mixture was associated with higher ADHD/noncompliance scores (median count ratio [CR] = 1.10; 2.5th, 97.5th percentile: 1.00, 1.21), especially hyperactivity/impulsivity (median CR = 1.09; 2.5th, 97.5th percentile: 1.00, 1.25). The possible contributors to these mixture effects were di-2-ethylhexyl phthalate (DEHP) metabolites and mono-2-heptyl phthalate (MHPP). These associations were likely driven by children with ASD as these were observed among children with ASD, but not among TD or those with DD. Additionally, among children with ASD, a mixture of all chemicals was associated with ADHD/noncompliance and hyperactivity/impulsivity, and possible contributors were 3,4-dihydroxy benzoic acid, DEHP metabolites, MHPP, mono-n-butyl phthalate, and cadmium.

Conclusions

Early childhood exposure to a phthalate mixture was associated with ADHD symptoms, particularly among children with ASD. While the diverse diagnostic profiles limited generalizability, our findings suggest a potential link between phthalate exposure and the comorbidity of ASD and ADHD.
Acceptance and feasibility of a low-threshold and substitution services-based periodical monitoring system for blood-borne and sexually transmitted infections among people who inject drugs in Germany: a mixed-methods analysis
Authors: Krings Amrei , Steffen Gyde , Zimmermann Ruth ,   the DRUCK 2.0-study group
Published: March 2024

Background

To reach the global elimination goals of viral hepatitis B and C (HBC, HCV), human immunodeficiency virus (HIV) and other sexually transmitted infections as a public health threat by 2030, monitoring is needed. Staff members of drug services and opioid substitution treatment (OST) practices in Berlin and Bavaria recruited clients for a pilot study addressing the respective infections among people who injected drugs (PWID) in Germany, 2021/2022. Participants filled a questionnaire and were tested for HBV, HCV, HIV and syphilis using dried blood spots (DBS). We evaluated the study design to implement a feasible and accepted nationwide periodical monitoring among PWID and serve as an example for the implementation of similar monitoring systems in other countries.

Methods

A mixed-methods design was used, including focus group discussions with study participants and staff members and a semi-quantitative questionnaire filled by the latter. Aspects covered were the setting for recruitment, study preparation for staff members, willingness of clients to participate, the study questionnaire, blood collection and return of results.

Results

The majority (96%) of 668 study participants were recruited in low-threshold services, drug consumption rooms and OST-practices. Flexibility of recruiting study participants during routine work or testing weeks/days was important to the facilities. Collaborations with local AIDS services helped cope with the work load of data collection. The need to train staff for DBS collection was highlighted. Study participants welcomed the testing opportunity in familiar places. Study participants frequently needed assistance to complete the study questionnaire. Return of results was considered as ethically mandatory by staff members but referral to treatment remained challenging.

Conclusions

For a successful monitoring time flexibility and adequate training are essential. Individual benefits for study participants by receiving their test results should be ensured and referral networks with infectiology practices may increase number of infected PWID receiving treatment. Overall, the evaluation confirmed that a monitoring through drug services and OST-practices is feasible and well accepted in Germany. Beyond that it shows important lessons learnt for the implementation in other countries.
Successful multidisciplinary treatment for synchronous advanced esophageal and cecal cancers after total gastrectomy with reconstruction by jejunal interposition
Authors: Sato Yuta , Tanaka Yoshihiro , Yamamoto Kazuo , Horaguchi Takeshi , Fukada Masahiro , Sengoku Yuki , Yasufuku Itaru , Asai Ryuichi , Tajima Jesse Yu , Kiyama Shigeru , Kato Takazumi , Murase Katsutoshi , Matsuhashi Nobuhisa
Published: March 2024

Background

Esophageal squamous cell carcinoma is characterized by field cancerization, wherein multiple cancers occur in the esophagus, head and neck, and stomach. Synchronous esophageal and colorectal cancers are also encountered with a certain frequency. A good prognosis can be expected if the tumors in both locations can be safely and completely removed. For patients with multiple cancers that occur simultaneously with esophageal cancer, it is necessary to perform a staged operation, taking into consideration the associated surgical invasiveness. It is also necessary to select multidisciplinary treatment depending on the degree of progression of the multiple lesions. We report our rare experience with a staged operation for a patient with synchronous advanced cancers of the esophagus and cecum who had previously undergone total gastrectomy with reconstruction by jejunal interposition for gastric cancer.

Case presentation

A 71-year-old man with a history of reconstruction by jejunal interposition after total gastrectomy was diagnosed as having multiple synchronous esophageal and cecal cancers. After neoadjuvant chemotherapy, we performed a planned two-stage operation, with esophagectomy and jejunostomy in the first stage and ileocecal resection and jejunal reconstruction with vascular anastomosis in the second. Postoperatively, the patient was relieved without major complications, and both tumors were amenable to curative pathologic resection.

Conclusions

Our procedure reported here may be recommended as an option for staged resection and reconstruction in patients with simultaneous advanced esophageal and cecal cancer after total gastrectomy.
Patient interest in the development of a center for Ehlers-Danlos syndrome/hypermobility spectrum disorder in the ﻿Chicagoland region
Authors: Wagner Wendy , Doyle Tom A. , Francomano Clair A. , Knight Dacre R. T. , Halverson Colin M. E.
Published: March 2024

Background

The Ehlers-Danlos Syndromes (EDS) are a group of connective tissue disorders that are hereditary in nature and characterized by joint hypermobility and tissue fragility. The complex nature of this unique patient population requires multidisciplinary care, but appropriate centers for such care do not exist in large portions of the country. Need for more integrated services has been identified in Chicagoland, or Chicago and its suburbs. In order to explore and begin to address barriers to seeking appropriate care facing EDS patients in this region, we developed an online survey which we circulated through EDS social media groups for Chicagoland patients.

Results

Three hundred and nine unique respondents participated. We found that there exists a strong medical need for and interest in the development of a center in the region, and participants reported that, if made available to them, they would make extensive and regular use of such a facility.

Conclusions

We conclude that the establishment of a collaborative medical center specializing in the diagnosis and treatment of EDS, Hypermobility Spectrum Disorder, and related disorders in the Chicagoland area would greatly benefit patients by providing comprehensive care, alleviate the burden on overworked healthcare providers, and contribute to the sustainability of medical facilities.
Photoautotrophic cultivation of a Chlamydomonas reinhardtii mutant with zeaxanthin as the sole xanthophyll
Authors: Kim Minjae , Cazzaniga Stefano , Jang Junhwan , Pivato Matteo , Kim Gueeda , Ballottari Matteo , Jin EonSeon
Published: March 2024

Background

Photosynthetic microalgae are known for their sustainable and eco-friendly potential to convert carbon dioxide into valuable products. Nevertheless, the challenge of self-shading due to high cell density has been identified as a drawback, hampering productivity in sustainable photoautotrophic mass cultivation. To address this issue, mutants with altered pigment composition have been proposed to allow a more efficient light diffusion but further study on the role of the different pigments is still needed to correctly engineer this process.

Results

We here investigated the Chlamydomonas reinhardtii Δzl mutant with zeaxanthin as the sole xanthophyll. The Δzl mutant displayed altered pigment composition, characterized by lower chlorophyll content, higher chlorophyll a/b ratio, and lower chlorophyll/carotenoid ratio compared to the wild type (Wt). The Δzl mutant also exhibited a significant decrease in the light-harvesting complex II/Photosystem II ratio (LHCII/PSII) and the absence of trimeric LHCIIs. This significantly affects the organization and stability of PSII supercomplexes. Consequently, the estimated functional antenna size of PSII in the Δzl mutant was approximately 60% smaller compared to that of Wt, and reduced PSII activity was evident in this mutant. Notably, the Δzl mutant showed impaired non-photochemical quenching. However, the Δzl mutant compensated by exhibiting enhanced cyclic electron flow compared to Wt, seemingly offsetting the impaired PSII functionality. Consequently, the Δzl mutant achieved significantly higher cell densities than Wt under high-light conditions.

Conclusions

Our findings highlight significant changes in pigment content and pigment–protein complexes in the Δzl mutant compared to Wt, resulting in an advantage for high-density photoautotrophic cultivation. This advantage is attributed to the decreased chlorophyll content of the Δzl mutant, allowing better light penetration. In addition, the accumulated zeaxanthin in the mutant could serve as an antioxidant, offering protection against reactive oxygen species generated by chlorophylls.
Cystic echinococcosis in cattle and sheep caused by Echinococcus granulosus sensu stricto genotypes G1 and G3 in the USA
Authors: Jesudoss Chelladurai Jeba R. J. , Quintana Theresa A. , Johnson William L. , Schmidt Carrie , Righter Daniel , Howey Erin
Published: March 2024

Background

Endemic domestic dog-ruminant cycles and human cystic echinococcosis caused by Echinococcus granulosus have been sporadically reported in the United States. However, there is a paucity of molecular data describing the genotypes and haplotypes of this important cestode in domestic ruminant hosts.

Methods

Ninety-four cysts from the lungs and/or livers of slaughtered beef cattle (76 samples), dairy cows (five samples) and sheep (13 samples) were collected from abattoirs in four states of the USA. Samples were genotyped at two mitochondrial loci, cox1 and nad5. Sequences were used to determine species, genotypes and haplotypes using median joining networks and Bayesian phylogenetic analyses. Cyst fertility was assessed in hematoxylin and eosin-stained sections. Additionally, previously reported autochthonous E. granulosus infections in the USA in various hosts were mapped.

Results

Based on cox1 sequences obtained from 94 cysts, 89 (94.7%) were identified as E. granulosus G1/G3, while five (5.3%) were Taenia hydatigena. Taenia hydatigena were only isolated from sheep. Based on nad5 sequences obtained from 89 hydatid cysts, 96.6% and 3.4% belonged to E. granulosus sensu stricto genotypes G1 and G3 respectively. Two haplotypes were found among E. granulosus cox1 sequences, neither of which was geographically unique. Six haplotypes were found among nad5 sequences in genotype G1, of which five were novel, while one haplotype was found in genotype G3. In the concatenated cox1-nad5 dataset, seven haplotypes were identified, of which six were geographically unique. All cysts from cattle were non-fertile. Four cysts from sheep were fertile.

Conclusions

All genotyped samples belonged to E. granulosus s.s. This is the first study to our knowledge to confirm the presence of genotypes G1 and G3 in domestic cattle and sheep intermediate hosts in the USA and provide data for future diagnostic and epidemiological studies. Sequences have been deposited in GenBank (cox1 sequences: OR398494-OR398496, nad5 sequences: OR400695-OR400702).

Graphical Abstract