bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of agitation in terminally ill patients with intranasal midazolam versus subcutaneous midazolam: study protocol for a randomised controlled open-label monocentric trial (MinTU Study)
Authors: Hirschinger Hanna , Jaeger Evelyn , Nittka Stefanie , Hetjens Svetlana , Lorenz Christine , Remi Constanze , Saussele Susanne , Hofmann Wolf-K. , Gencer Deniz , Boch Tobias
Published: January 2024

Background

Intranasal (i.n.) drug application is a widely known and low-invasive route of administration that may be able to achieve rapid symptom control in terminally ill patients. According to the German S3 guideline “Palliative care for patients with incurable cancer”, benzodiazepines, such as midazolam, are recommended for the treatment of terminal agitation. To the best of our knowledge there is no evidence for i.n. midazolam in terminally ill patients. We aim to assess the use of i.n. midazolam as an alternative to subcutaneous administration of the drug.

Methods

In this monocentric, randomised, controlled, open-label investigator initiated trial, n = 60 patients treated at the palliative care unit of a University Hospital will be treated with 5 mg midazolam i.n. versus 5 mg subcutaneous (s.c.) midazolam in the control arm when terminal agitation occurs (randomly assigned 1:1). The estimated recruitment period is 18 months. Treatment efficacy is defined as an improvement on the Richmond Agitation Sedation Scale (Palliative Version) (RASS-PAL) and a study specific numeric rating scale (NRS) before and after drug administration. Furthermore, plasma concentration determinations of midazolam will be conducted at t1 = 0 min, t2 = 5 min, and t3 = 20 min using liquid chromatography/mass spectrometry (LC-MS). The primary objective is to demonstrate non-inferiority of midazolam i.n. in comparison to midazolam s.c. for the treatment of agitation in terminally ill patients.

Discussion

Midazolam i.n. is expected to achieve at least equivalent reduction of terminal agitation compared to s.c. administration. In addition, plasma concentrations of midazolam i.n. are not expected to be lower than those of midazolam s.c. and the dynamics of the plasma concentration with an earlier increase could be beneficial.

Trial registration

German Clinical Trials Registry DRKS00026775, registered 07.07.2022, Eudra CT No.: 2021-004789-36.
Interprofessional communication skills training to improve medical students’ and nursing trainees’ error communication - quasi-experimental pilot study
Authors: Heier Lina , Schellenberger Barbara , Schippers Anna , Nies Sebastian , Geiser Franziska , Ernstmann Nicole
Published: January 2024

Background

Interprofessional communication is of extraordinary importance for patient safety. To improve interprofessional communication, joint training of the different healthcare professions is required in order to achieve the goal of effective teamwork and interprofessional care. The aim of this pilot study was to develop and evaluate a joint training concept for nursing trainees and medical students in Germany to improve medication error communication.

Methods

We used a mixed-methods, quasi-experimental study with a pre-post design and two study arms. This study compares medical students (3rd year) and nursing trainees (2nd year) who received an interprofessional communication skills training with simulation persons (intervention group, IG) with a control group (CG). Both cohorts completed identical pre- and post-training surveys using the German Interprofessional Attitudes Scale (G-IPAS) and a self-developed interprofessional error communication scale. Descriptive statistics, Mann-Whitney-U-test and Wilcoxon-test were performed to explore changes in interprofessional error communication.

Results

A total of 154 were medical students, and 67 were nursing trainees (IG: 66 medical students, 28 nursing trainees / CG: 88 medical students, 39 nursing trainees). After training, there were significant improvements observed in the “interprofessional error communication” scale (p < .001) and the “teamwork, roles, and responsibilities” subscale (p = .012). Median scores of the subscale “patient-centeredness” were similar in both groups and remained unchanged after training (median = 4.0 in IG and CG).

Conclusions

Future studies are needed to find out whether the training sustainably improves interprofessional teamwork regarding error communication in acute care.
How nursing practice environments limit implicit rationing of care and nurse-assessed adverse events: the role of flow at work
Authors: El-Gazar Heba E. , Abousoliman Ali D , Shawer Mona , Coelho Paulo , Zoromba Mohamed A.
Published: January 2024

Background

The nursing practice environment is beneficial in curbing implicit rationing of nursing care and adverse patient events. However, the underlying mechanisms of these relationships remain unexplored.

Aim

To test whether flow at work mediates the relationship between the nursing practice environment, implicit rationing of nursing care, and nurse-assessed adverse patient events.

Methods

This cross-sectional study involved 231 nurses from five hospitals in Port Said, Egypt. The participants completed Arabic-translated versions of the Practice Environment Scale of the Nursing Work Index, the Work-Related Flow Inventory, the Perceived Implicit Rationing of Nursing Care instrument, and the Adverse Patient Events scale. Structural equation modeling was used to test the hypothetical model.

Results

The favorable nursing practice environment positively predicted nurses’ flow at work (β = 0.64, p < 0.001), while inversely predicting implicit rationing of nursing care (β = -0.23, p = 0.014) and adverse patient events (β = -0.35, p < 0.001). Nurses’ flow at work inversely predicted implicit rationing of nursing care (β = -0.30, p = 0.002) and adverse patient events (β = -0.29, p = 0.002). Moreover, nurses’ flow at work acted as a mediator, linking the nursing practice environment to the rationing of nursing care and adverse patient events, with 500 bootstrap results for the indirect effects (β = -0.24, p = 0.001, 95% CI: -0.43 to -0.09; and β = -0.44, p = 0.003, 95% CI: -0.79 to -0.16, respectively).

Conclusion

Nurses working in a favorable nursing practice environment are more likely to experience flow at work, limiting implicit rationing of nursing care and adverse patient events.

Implications for nursing management

Nursing administrators should strive to create a healthy nursing practice environment to foster nurses’ flow and thereby reduce the frequency of implicit rationing of nursing care and adverse patient events.
Rural and regional maternity managers’ and educators’ views of the Maternity and Newborn Emergencies (MANE) education program in Victoria, Australia: a qualitative descriptive study
Authors: Zugna Stefanie A , McLachlan Helen L , Cullinane Meabh , Newton Michelle , Forster Della A
Published: January 2024

Background

Australia has one of the lowest perinatal morbidity and mortality rates in the world, however a cluster of perinatal deaths at a regional health service in the state of Victoria in 2015 led to state-wide reforms, including the introduction of the Maternity and Newborn Emergencies (MANE) program. MANE was a 2-day interprofessional maternity education program delivered by external expert facilitators to rural and regional Victorian maternity service providers. An independent evaluation found that the MANE program improved the confidence and knowledge of clinicians in managing obstetric emergencies and resulted in changes to clinical practice. While there is a large volume of evidence that supports the use of interprofessional education in improving clinicians’ clinical practice, the impact of these programs on the overall safety culture of a health service has been less studied. Managers and educators have an important role in promoting the safety culture and clinical governance of the heath service. The aim of this study, therefore, was to explore Victorian rural and regional maternity managers’ and educators’ views and experiences of the MANE program.

Methods

Maternity managers and educators from the 17 regional and rural health services across Victoria that received the MANE program during 2018 and 2019 were invited to participate. Semi-structured interviews using mostly open-ended questions (and with a small number of fixed response questions) were undertaken. Qualitative data were transcribed verbatim and analysed thematically. Descriptive statistics were used for quantitative data.

Results

Twenty-one maternity managers and educators from the 17 health services participated in the interviews. Overall, participants viewed the MANE program positively. Four themes were identified: the value of external facilitation in providing obstetric emergency training; improved awareness and understanding of clinical governance; improved clinical practice; and the importance of maintaining the program. Participants agreed that MANE had improved the confidence (94%) and skills (94%) of clinicians in managing obstetric emergencies, as well as confidence to escalate concerns (94%), and most agreed that it had improved clinical practice (70%) and teamwork among attendees (82%).

Conclusion

Maternity managers and educators were positive about MANE; they considered that it contributed to improving factors that impact the safety culture of health services, with delivery by external experts considered to be particularly important. Given the crucial role of maternity managers and educators on safety culture in health services, as well in program facilitation, these findings are important for future planning of maternity education programs across the state.

Trial registration

Trial registration was not required for this study.
Qualitative realist evaluation of an occupational therapy intervention programme (ABLE), addressing ability to perform activities of daily living among persons with chronic conditions
Authors: Hagelskjær Vita , Wæhrens Eva Ejlersen , von Bülow Cecilie , Nielsen Kristina Tomra
Published: January 2024

Background

Chronic conditions are associated with problems related to performance of activities of daily living (ADL) stressing a need to develop and evaluate intervention programmes addressing such problems. Hence, the ABLE programme was developed, and its feasibility evaluated. Implementing intervention programmes in community-based rehabilitation settings requires understanding of how the programme works in various contexts. Applying a realist evaluation approach, the aim of this study was to identify and evaluate interactions between contexts, mechanisms, and outcomes in the ABLE 2.0, to confirm, refine, or reject aspects of the initial programme theory.

Methods

Realist evaluation using qualitative data collected in the ABLE 2.0 randomised controlled trial (n = 78). Based on the ABLE 2.0 initial programme theory, qualitative realist interviews were conducted among receivers (n = 8) and deliverers (n = 3) of the ABLE 2.0 in a Danish municipality. Transcripts were coded, and context-mechanism-outcome configurations were extracted and grouped into contiguous themes. Results were then held up against the initial programme theory.

Results

Four contiguous themes were identified including a total of n = 28 context-mechanism-outcome configurations: building a foundation for the entire intervention; establishing the focus for further intervention; identifying and implementing relevant compensatory solutions; and re-evaluating ADL ability to finalise intervention. Overall, the ABLE 2.0 initial programme theory was confirmed. The evaluation added information on core facilitating mechanisms including active involvement of the client in the problem-solving process, a collaborative working relationship, mutual confidence, and a consultative occupation-based process using compensatory solutions. Several contextual factors were required to activate the desired mechanisms in terms of supportive management, referral procedures encouraging the problem-solving process, delivery in the client’s home, skilled occupational therapists, and clients feeling ready for making changes.

Conclusions

The ABLE 2.0 represents a coherent problem-solving occupational therapy process, applicable across sex, age, and diagnoses with the potential to enhance ADL ability among persons with chronic conditions, when delivered as part of community-based rehabilitation services. Knowledge about the interactions between contextual factors, mechanisms, and outcomes in the ABLE 2.0 is central in case of future implementation of the programme in community-based rehabilitation settings.

Trial registration

The trial was prospectively registered on www.ClinicalTrials.gov (registration date: 05/03/2020; identifier: NCT04295837) prior to data collection that occurred between August 2020 and October 2021.
Abomasitis associated with halofuginone intoxication in pre-weaned calves
Authors: van Mol Wouter , Chantillon Laurens , Geerinckx Lise , Coppens Jolien , Clinquart Justine , Pas Mathilde , Bokma Jade , Pardon Bart
Published: January 2024

Background

In this case series abomasitis as a consequence of halofuginone intoxication is suspected.

Case presentation

Seven Belgian-Blue calves with complaints of anorexia and weight loss were presented to an university clinic. Ultrasonography showed thickening and edema of the abomasal wall in all cases, suggesting abomasitis. Abomasitis was confirmed on necropsy in three cases. Retrospective analysis clarified the uptake of an overdose of halofuginone lactate (348–421 µg/kg/day). Four animals fully recovered after removal of halofuginone lactate administration, therapy for comorbidities (pneumonia, diarrhoea) and supportive therapy.

Conclusion

To the authors’ knowledge, this case series is the first report associating halofuginone lactate use with abomasitis. This was suspected after clinical improvement of four of the presented animals after terminating the administration of a high dose of halofuginone lactate, and exclusion of other possible causes. Underlying mechanisms are still unclear.
Addition of low concentration of cholesterol-loaded cyclodextrin (CLC) has a positive effect on cryopreserved canine spermatozoa evaluated by andrological and biophysical methods
Authors: Ligocka Zuzanna , Partyka Agnieszka , Bonarska-Kujawa Dorota , Mucha Anna , Niżański Wojciech
Published: January 2024

Background

This study was conducted to find the best concentration of cholesterol-loaded cyclodextrin (CLC) which has a positive impact on canine post thaw semen quality. Three different concentrations of CLC (0.83 mg/ml; 1.66 mg/ml; 3.32 mg/ml) and 2-hydroxylpropyl-beta-cyclodextrin (HBCD) (1.66 mg/ml) were used in addition to cryopreservation extender and compared with the control after thawing. Samples were assessed using computer-assisted semen analyzer (CASA), flow cytometry, fluorimeter by measuring the fluorescence anisotropy (ANISO) and determining the generalized membrane polarization (GP).

Results

An addition of 0.83 mg/ml CLC significantly increased the percentage of progressive motile (PROG) and rapid spermatozoa (RAP) (P < 0.05). 1.66 mg/ml HBCD decreased progressive motility of spermatozoa and population with rapid movement relative to the control (P < 0.05). Furthermore, the groups with an addition of 1.66 mg/ml and 3.32 mg/ml of CLC, as well as the group with only cyclodextrin, increased percentage of dead spermatozoa without lipid peroxidation and decreased percentage of viable spermatozoa without LPO which was lower in these groups than in the control (P < 0.05). Other sperm parameters assessed on flow cytometer were not significantly different. The addition of CLC at 0.83 mg/ml and 3.32 mg/ml concentrations and 1.66 mg/ml of HBCD caused an increase in ANISO measured at 23 ºC (P < 0.05).

Conclusions

In conclusion, the results suggest that increasing cholesterol in the plasma membrane of canine spermatozoa can improve their freezability. However, only low concentrations of CLC may improve semen quality after thawing without adversely affecting other parameters.
Detection and molecular analysis of Pseudorabies virus from free-ranging Italian wolves (Canis lupus italicus) in Italy - a case report
Authors: Moreno Ana , Musto Carmela , Gobbi Marco , Maioli Giulia , Menchetti Marika , Trogu Tiziana , Paniccià Marta , Lavazza Antonio , Delogu Mauro
Published: January 2024

Background

The only natural hosts of Pseudorabies virus (PRV) are members of the family Suidae (Sus scrofa scrofa). In mammals, the infection is usually fatal and typically causes serious neurologic disease. This study describes four Aujeszky’s disease cases in free-ranging Italian wolves (Canis lupus italicus). In Italy, the wolf is a strictly protected species and is in demographic expansion.

Case presentation

Three wolves (Wolf A, B, and C) were found in a regional park in Northern Italy, and one (Wolf D) was found in Central Italy. Wolf A and D were alive at the time of the finding and exhibited a fatal infection with epileptic seizures and dyspnoea, dying after a few hours. Wolf B presented scratching lesions under the chin and a detachment of the right earlobe, whilst Wolf C was partially eaten.

The wolves showed hepatic congestion, diffuse enteritis, moderate pericardial effusion, severe bilateral pneumonia, and diffuse hyperaemia in the brain. The diagnostic examinations included virological analyses and detection of toxic molecules able to cause serious neurological signs.

All four wolves tested positive for pseudorabies virus (PrV). The analysed sequences were placed in Italian clade 1, which is divided into two subclades, “a” and “b”. The sequences of Wolf A, B, and C were closely related to other Italian sequences in the subclade b, originally obtained from wild boars and hunting dogs. The sequence from Wolf D was located within the same clade and was closely related to the French hunting dog sequences belonging to group 4.

Conclusion

Results showed the presence of PrV strains currently circulating in wild boars and free-ranging Italian wolves. The genetic characterisation of the PrV UL44 sequences from the four wolves confirmed the close relationship with the sequences from wild boars and hunting dogs. This fact supports a possible epidemiological link with the high PrV presence in wild boars and the possibility of infection in wolves through consumption of infected wild boar carcasses or indirect transmission. To the best of our knowledge, this study is the first detection of Pseudorabies virus in free-ranging Italian wolves in northern and central Italy.
Using time-series chest radiographs and laboratory data by machine learning for identifying pulmonary infection and colonization of Acinetobacter baumannii
Authors: Zeng Zhaodong , Wu Jiefang , Qin Genggeng , Yu Dong , He Zilong , Zeng Weixiong , Zhou Hao , Lin Jiongbin , Liu Laiyu , Qi Chunxia , Chen Weiguo
Published: January 2024

Background

Accurately distinguishing between pulmonary infection and colonization in patients with Acinetobacter baumannii is of utmost importance to optimize treatment and prevent antibiotic abuse or inadequate therapy. An efficient automated sorting tool could prompt individualized interventions and enhance overall patient outcomes. This study aims to develop a robust machine learning classification model using a combination of time-series chest radiographs and laboratory data to accurately classify pulmonary status caused by Acinetobacter baumannii.

Methods

We proposed nested logistic regression models based on different time-series data to automatically classify the pulmonary status of patients with Acinetobacter baumannii. Advanced features were extracted from the time-series data of hospitalized patients, encompassing dynamic pneumonia indicators observed on chest radiographs and laboratory indicator values recorded at three specific time points.

Results

Data of 152 patients with Acinetobacter baumannii cultured from sputum or alveolar lavage fluid were retrospectively analyzed. Our model with multiple time-series data demonstrated a higher performance of AUC (0.850, with a 95% confidence interval of [0.638–0.873]), an accuracy of 0.761, a sensitivity of 0.833. The model, which only incorporated a single time point feature, achieved an AUC of 0.741. The influential model variables included difference in the chest radiograph pneumonia score.

Conclusion

Dynamic assessment of time-series chest radiographs and laboratory data using machine learning allowed for accurate classification of colonization and infection with Acinetobacter baumannii. This demonstrates the potential to help clinicians provide individualized treatment through early detection.
Biochemical and transcriptomic evaluation of a 3D lung organoid platform for pre-clinical testing of active substances targeting senescence
Authors: Brand Michelle , Ritzmann Felix , Kattler Kathrin , Milasius Deivydas , Yao Yiwen , Herr Christian , Kirsch Susanne H. , Müller Rolf , Yildiz Daniela , Bals Robert , Beisswenger Christoph
Published: January 2024

Chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis are incurable. Epithelial senescence, a state of dysfunctional cell cycle arrest, contributes to the progression of such diseases. Therefore, lung epithelial cells are a valuable target for therapeutic intervention. Here, we present a 3D airway lung organoid platform for the preclinical testing of active substances with regard to senescence, toxicity, and inflammation under standardized conditions in a 96 well format. Senescence was induced with doxorubicin and measured by activity of senescence associated galactosidase. Pharmaceutical compounds such as quercetin antagonized doxorubicin-induced senescence without compromising organoid integrity. Using single cell sequencing, we identified a subset of cells expressing senescence markers which was decreased by quercetin. Doxorubicin induced the expression of detoxification factors specifically in goblet cells independent of quercetin. In conclusion, our platform enables for the analysis of senescence-related processes and will allow the pre-selection of a wide range of compounds (e.g. natural products) in preclinical studies, thus reducing the need for animal testing.
Association of long-term triglyceride-glucose index patterns with the incidence of chronic kidney disease among non-diabetic population: evidence from a functional community cohort
Authors: Chen Ning , Ma Lin-Lin , Zhang Yu , Chu Xi , Dong Jing , Yan Yu-Xiang
Published: January 2024

Background

The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and previous studies have confirmed the association of TyG index with incident chronic kidney disease (CKD). However, the impact of longitudinal patterns of TyG index on CKD risk among non-diabetic population is still unknown. Therefore, this study aimed to investigate the association of longitudinal patterns of TyG index with incident CKD among non-diabetic population.

Methods

A total of 5484 non-diabetic participants who underwent one health examination per year from 2015 to 2017 were included in this prospective study. TyG index variability and cumulative TyG index were calculated to assess the longitudinal patterns of TyG index. Cox proportional hazard models were performed to estimate the association of TyG index variability or cumulative TyG index with incident CKD.

Results

During a median of 3.82 years follow-up, 879 participants developed CKD. Compared with participants in the lowest quartile, the hazard ratio (HR) and 95% confidence interval (CI) of incident CKD were 1.772 (95% CI: 1.453, 2.162) for the highest TyG index variability quartile and 2.091 (95% CI: 1.646, 2.655) for the highest cumulative TyG index quartile in the fully adjusted models. The best discrimination and reclassification improvement were observed after adding baseline TyG, TyG index variability and cumulative TyG index to the clinical risk model for CKD.

Conclusions

Both TyG index variability and cumulative TyG index can independently predict incident CKD among non-diabetic population. Monitoring longitudinal patterns of TyG index may assist with prediction and prevention of incident CKD.
Encapsulation and assessment of therapeutic cargo in engineered exosomes: a systematic review
Authors: Chen Zhen , Xiong Min , Tian Jiaqi , Song Dandan , Duan Shuyin , Zhang Lin
Published: January 2024

Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies.

Graphical Abstract
A continuously efficient O2-supplying strategy for long-term modulation of hypoxic tumor microenvironment to enhance long-acting radionuclides internal therapy
Authors: Li Jingchao , Wang Tingting , Shi Yuanfei , Ye Zichen , Zhang Xun , Ming Jiang , Zhang Yafei , Hu Xinyan , Li Yun , Zhang Dongsheng , Xu Qianhe , Yang Jun , Chen Xiaolan , Liu Nian , Su Xinhui
Published: January 2024

Radionuclides internal radiotherapy (RIT) is a clinically powerful method for cancer treatment, but still poses unsatisfactory therapeutic outcomes due to the hypoxic characteristic of tumor microenvironment (TME). Catalase (CAT) or CAT-like nanomaterials can be used to enzymatically decompose TME endogenous H2O2 to boost TME oxygenation and thus alleviate the hypoxic level within tumors, but their effectiveness is still hindered by the short-lasting of hypoxia relief owing to their poor stability or degradability, thereby failing to match the long therapeutic duration of RIT. Herein, we proposed an innovative strategy of using facet-dependent CAT-like Pd-based two-dimensional (2D) nanoplatforms to continuously enhance RIT. Specifically, rationally designed 2D Pd@Au nanosheets (NSs) enable consistent enzymatic conversion of endogenous H2O2 into O2 to overcome hypoxia-induced RIT resistance. Furthermore, partially coated Au layer afford NIR-II responsiveness and moderate photothermal treatment that augmenting their enzymatic functionality. This approach with dual-effect paves the way for reshaping TME and consequently facilitating the brachytherapy ablation of cancer. Our work offers a significant advancement in the integration of catalytic nanomedicine and nuclear medicine, with the overarching goal of amplifying the clinical benefits of RIT-treated patients.

Graphical abstract
Nano-carrier DMSN for effective multi-antigen vaccination against SARS-CoV-2
Authors: Sun Peng , Cheng Bingsheng , Ru Jiaxi , Li Xiaoyan , Fang Guicun , Xie Yinli , Shi Guangjiang , Hou Jichao , Zhao Longwei , Gan Lipeng , Ma Lina , Liang Chao , Chen Yin , Li Zhiyong
Published: January 2024

The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has had a profound impact on the global health and economy. While mass vaccination for herd immunity is effective, emerging SARS-CoV-2 variants can evade spike protein-based COVID-19 vaccines. In this study, we develop a new immunization strategy by utilizing a nanocarrier, dendritic mesoporous silica nanoparticle (DMSN), to deliver the receptor-binding domain (RBD) and conserved T-cell epitope peptides (DMSN-P-R), aiming to activate both humoral and cellular immune responses in the host. The synthesized DMSN had good uniformity and dispersion and showed a strong ability to load the RBD and peptide antigens, enhancing their uptake by antigen-presenting cells (APCs) and promoting antigen delivery to lymph nodes. The DMSN-P-R vaccine elicited potent humoral immunity, characterized by highly specific RBD antibodies. Neutralization tests demonstrated significant antibody-mediated neutralizing activity against live SARS-CoV-2. Crucially, the DMSN-P-R vaccine also induced robust T-cell responses that were specifically stimulated by the RBD and conserved T-cell epitope peptides of SARS-CoV-2. The DMSN demonstrated excellent biocompatibility and biosafety in vitro and in vivo, along with degradability. Our study introduces a promising vaccine strategy that utilizes nanocarriers to deliver a range of antigens, effectively enhancing both humoral and cellular immune responses to prevent virus transmission.
Multifunctional Fe-based coordination polymer nano-bomb modified with β-lapachone and CaO2 for targeted tumor dual chemodynamic therapy with enhanced ferroptosis and H2O2 self-supply
Authors: Zhao Pan , Gong Liyang , Chang Le , Du Huiping , Geng Meijuan , Meng Siyu , Dai Liangliang
Published: January 2024

Chemodynamic therapy (CDT) is seriously limited by the inadequacy of exogenous catalytic ions and endogenous H2O2 in tumors. Herein, a multifunction nano-bomb integrated with calcium peroxide (CaO2) and β-lapachone as donors of H2O2 and GSH-sensitive Fe-based coordination polymer as provider of catalytic ions was constructed for dual cascade-amplified tumor CDT. This hyaluronic acid (HA)-modified nano-bomb could be specially endocytosed by breast cancer cells through a targeting pathway, degraded and released cargoes in response to the GSH-rich cytoplasm. Furthermore, the released CaO2 and β-lapachone could significantly self-generated sufficient H2O2, which could dual-cascade amplify CDT and induce severe oxidative to tumors via cooperating with the delivered iron ions from nano-bombs. Moreover, the unloaded iron and calcium ions could further accelerate tumor damage by overloading Ca2+ and ferroptosis, as accompanied by good magnetic resonance imaging (MRI). In vitro and in vivo studies collectively reveal that this nano-bomb not only self-initiates double cascade-amplified CDT via self-generation of H2O2, but also efficiently activates ferroptosis and initiates Ca2+ overloading, consequently significantly tumor growth suppression. This study offers a novel tumor-initiated nano-bomb for dual cascade-amplified CDT and bioimaging with activated ferroptosis and self-supplying H2O2.
Willingness to use and distribute HIV self-testing kits among people who inject drugs in the San Diego–Tijuana border region
Authors: Pines Heather A. , Eger William H. , Skaathun Britt , Vera Carlos F. , Harvey-Vera Alicia , Rangel Gudelia , Strathdee Steffanie A. , Bazzi Angela R.
Published: January 2024

Background

HIV self-testing (HIVST) could increase HIV testing access among people who inject drugs (PWID), and secondary distribution (i.e., peer-delivery) of HIVST kits in PWID social networks could further expand coverage. We assessed willingness to use and distribute HIVST kits among PWID in the San Diego–Tijuana border region.

Methods

From 2020 to 2021, HIV-negative PWID in San Diego, USA, and Tijuana, Mexico, completed surveys and provided data on individual (N = 539) and social network (N = 366) characteristics. We used modified Poisson regression to examine the effects of individual and social network characteristics on willingness to use and distribute HIVST kits.

Results

Most participants were willing to use (81%) and distribute (81%) HIVST kits. At the individual level, prior HIV testing was positively associated with willingness to use (adjusted prevalence ratio [aPR] = 1.24, 95% confidence interval [CI] 1.10–1.40) and distribute (aPR = 1.27, 95% CI 1.12–1.43) HIVST kits, while perceiving oneself to be at higher HIV risk than others was negatively associated with willingness to use HIVST kits (aPR = 0.83, 95% CI 0.74–0.93). At the network level, willingness to distribute HIVST kits was positively associated with network size (aPR = 1.04 per member, 95% CI 1.01–1.08) and greater proportions of one’s network encouraging them to use drugs (aPR = 1.29, 95% CI 1.16–1.44) and having a history of homelessness (aPR = 1.51, 95% CI 1.31–1.74) or detention/arrest (aPR = 1.57, 95% CI 1.36–1.82), and negatively associated with a greater proportion of one’s network including “very close” persons (aPR = 0.80, 95% CI 0.69–0.94).

Conclusions

We found high potential for HIVST kits and their secondary distribution to increase HIV testing among PWID who face the greatest barriers to facility-based testing.
Virus-like particle-mediated delivery of structure-selected neoantigens demonstrates immunogenicity and antitumoral activity in mice
Authors: Barajas Ana , Amengual-Rigo Pep , Pons-Grífols Anna , Ortiz Raquel , Gracia Carmona Oriol , Urrea Victor , de la Iglesia Nuria , Blanco-Heredia Juan , Anjos-Souza Carla , Varela Ismael , Trinité Benjamin , Tarrés-Freixas Ferran , Rovirosa Carla , Lepore Rosalba , Vázquez Miguel , de Mattos-Arruda Leticia , Valencia Alfonso , Clotet Bonaventura , Aguilar-Gurrieri Carmen , Guallar Victor , Carrillo Jorge , Blanco Julià
Published: January 2024

Background

Neoantigens are patient- and tumor-specific peptides that arise from somatic mutations. They stand as promising targets for personalized therapeutic cancer vaccines. The identification process for neoantigens has evolved with the use of next-generation sequencing technologies and bioinformatic tools in tumor genomics. However, in-silico strategies for selecting immunogenic neoantigens still have very low accuracy rates, since they mainly focus on predicting peptide binding to Major Histocompatibility Complex (MHC) molecules, which is key but not the sole determinant for immunogenicity. Moreover, the therapeutic potential of neoantigen-based vaccines may be enhanced using an optimal delivery platform that elicits robust de novo immune responses.

Methods

We developed a novel neoantigen selection pipeline based on existing software combined with a novel prediction method, the Neoantigen Optimization Algorithm (NOAH), which takes into account structural features of the peptide/MHC-I interaction, as well as the interaction between the peptide/MHC-I complex and the TCR, in its prediction strategy. Moreover, to maximize neoantigens’ therapeutic potential, neoantigen-based vaccines should be manufactured in an optimal delivery platform that elicits robust de novo immune responses and bypasses central and peripheral tolerance.

Results

We generated a highly immunogenic vaccine platform based on engineered HIV-1 Gag-based Virus-Like Particles (VLPs) expressing a high copy number of each in silico selected neoantigen. We tested different neoantigen-loaded VLPs (neoVLPs) in a B16-F10 melanoma mouse model to evaluate their capability to generate new immunogenic specificities. NeoVLPs were used in in vivo immunogenicity and tumor challenge experiments.

Conclusions

Our results indicate the relevance of incorporating other immunogenic determinants beyond the binding of neoantigens to MHC-I. Thus, neoVLPs loaded with neoantigens enhancing the interaction with the TCR can promote the generation of de novo antitumor-specific immune responses, resulting in a delay in tumor growth. Vaccination with the neoVLP platform is a robust alternative to current therapeutic vaccine approaches and a promising candidate for future personalized immunotherapy.
Benign Metastasizing Leiomyoma: New insights into a rare disease with an obscure etiopathogenesis
Authors: Chouchane Aziz , Boughizane Sassi , Nouira Monia , Remadi Sami
Published: January 2024

Background

Benign metastasizing leiomyoma (BML) is a rare disease with an unknown etiopathogenesis that mostly affects middle-aged women with uterine leiomyoma. Many metastatic nodules outside the uterus characterize the condition. The metastases are smooth muscle lesions without malignancy. Morphologically and immunohistochemically, they resemble uterine leiomyomas, indicating a shared clonal origin. The lungs are the most prevalent site for incidental metastasis detection. BML has a relatively slow progression and good prognosis, and historically, there has been a lack of established guidelines for its treatment.

Case presentation

Herein, we report a case of BML in a patient with multiple metastases. Through extensive histological and immunohistochemical analyses, this complex case enabled not only the definitive diagnosis of BML, but also shed light on its complex etiopathogenesis.

Conclusion

This study presents novel histology evidence suggesting a potential causal relationship between metaplasia and the development of BML.
Physicochemical properties of AH plus bioceramic sealer, Bio-C Sealer, and ADseal root canal sealer
Authors: Hamdy Tamer M. , Galal Manar M. , Ismail Amira Galal , Saber Shehabeldin
Published: January 2024

Background

The aim of this study was to evaluate the physicochemical properties of two newly introduced premixed calcium silicate-based root canal sealers (AH Plus Bioceramic Sealer and Bio-C Sealer) compared to a resin-based root canal sealer (ADseal root canal sealer).

Methods

Solubility, pH analysis, calcium ion release, and film thickness of each sealer were evaluated following ISO guidelines. The data were examined using the two-way ANOVA test. Furthermore, X-ray diffraction (XRD) examination was performed to investigate the crystalline phase of each type of sealer. X-ray fluorescence (XRF) analysis was done for the chemical elemental analysis of each sealer.

Results

The least film thickness, highest alkalinity, and highest calcium ion release were all displayed by AH Plus Bioceramic Sealer. High solubility, high alkalinity, intermediate calcium ion release, and intermediate film thickness were all displayed by Bio-C Sealer. While ADseal root canal sealer displayed the greatest film thickness, least solubility, alkalinity, and calcium ion release.

Conclusions

Both AH Plus Bioceramic Sealer and Bio-C Sealer represented adequate properties to be considered a good sealer that could be used as a potential alternative to resin-based root canal sealers.
Shared decision-making and client-reported dose satisfaction in a longitudinal cohort receiving injectable opioid agonist treatment (iOAT)
Authors: Beaumont Scott , Magel Tianna , MacDonald Scott , Harrison Scott , Schechter Martin , Oviedo-Joekes Eugenia
Published: January 2024

Background

Across different types of oral Opioid Agonist Treatment for people with Opioid Use Disorder, receiving a dose that meets their needs is associated with better outcomes. Evidence also shows patients are more likely to receive an “adequate dose” when their prescribers are involving them in decision making. Neither of these findings have been studied in the context of injectable Opioid Agonist Treatment, which is the purpose of this study.

Methods

This study was a retrospective analysis of an 18-month prospective longitudinal cohort study of 131 people receiving injectable Opioid Agonist Treatment. In the 18-month study, observations were collected every two months for one year, and then once more at 18 months. At 6 months, participants were asked whether their dose was satisfactory to them (outcome variable). Generalized Estimating Equations were used, to account for multiple observations from each participant. The final multivariate model was built using a stepwise approach.

Results

Five hundred forty-five participant-observations were included in the analysis. Participant-observations were grouped by “dose is satisfactory” and “wants higher dose”. From unadjusted analyses, participants were less likely to report being satisfied with their dose if they: were Indigenous, had worse psychological or physical health problems, had ever attempted suicide, were younger when they first injected any drug, were a current smoker, felt troubled by drug problems, gave their medication a lower “drug liking” score, and felt that their doctor was not including them in decisions the way they wanted to be. In the final multivariate model, all previously significant associations except for “current smoker” and “troubled by drug problems” were no longer significant after the addition of the “drug liking” score.

Conclusions

Patients in injectable Opioid Agonist Treatment who are not satisfied with their dose are more likely to: be troubled by drug problems, be a current smoker, and report liking their medication less than dose-satisfied patients. Prescribers’ practicing shared decision-making can help patients achieve dose-satisfaction and possibly alleviate troubles from drug problems. Additionally, receiving a satisfactory dose may be dependent on patients being able to access an opioid agonist medication (and formulation) that they like.
Development of a low back pain care pathway in an academic hospital system: results of a consensus process
Authors: Bejarano Geronimo , Vining Robert , Desai Devan P. , Minchew Joe , Michael Guo H. , Goertz Christine
Published: January 2024

Background

Low back pain (LBP) is the leading cause of disability worldwide and a significant component of healthcare expenditures. Clinical practice guidelines (CPGs) have been highlighted as a key resource to improve the quality of care. This study aimed to develop a clinical pathway for LBP based on CPGs in an academic health system.

Methods

We conducted a modified Delphi study of clinicians caring for patients with LBP who were asked to rate 21 CPG-informed seed statements through an online survey. The goal was to identify statements that achieved a minimum of 80% consensus among panelists.

Results

Thirty-five healthcare providers participated as panelists. The majority of participants were male (68.6%), had MD or DO (62.9%) degrees, and were clinicians (73.8%) working in neurosurgery (36.1%), orthopedics (25.7%), emergency medicine (14.3%), or physical therapy (11.4%). Initially, consensus was reached on 20 of 21 seed statements. One statement did not reach consensus in the initial round and was revised into two separate statements based on feedback from panelists. One of these statements achieved consensus in the second review round. All statements reaching consensus were incorporated into a care pathway consisting of diagnosis, evaluation, and treatment for LBP.

Conclusion

Healthcare providers across various disciplines supported statements interpreting current CPGs related to care for LBP. This study represents a step toward supporting guideline-concordant care for LBP. Additional research is needed to assess how such pathways impact actual clinical care.
Therapeutic effects of extracorporeal shock wave therapy on patients with spastic cerebral palsy and Rett syndrome: clinical and ultrasonographic findings
Authors: Su Ting-Yu , Huang Yu-chi , Ko Jih-Yang , Hsin Yi-Jung , Yu Min-Yuan , Hung Pi-Lien
Published: January 2024

Background

Extracorporeal shock wave therapy (ESWT) is reportedly effective for improving spasticity and motor function in children with cerebral palsy (CP). Because late-stage Rett syndrome has a similar presentation, this study aimed to investigate the effects of ESWT on these two diseases.

Material and Methods

Patients diagnosed with spastic CP and Rett syndrome received 1500 impulses of ESWT at 4 Hz and 0.1 mJ/mm2, on their spastic legsonce weekly for a total of 12 weeks. Outcomes were assessed before and 4 and 12 weeks after ESWT. Clinical assessments included the Modified Ashworth Scale (MAS), passive range of motion (PROM), and Gross Motor Function Measure 88 (GMFM-88). Ultrasonographic assessments included muscle thickness, acoustic radiation force impulse (ARFI), and strain elastography.

Results

Fifteen patients with CP and six with Rett syndrome were enrolled in this study. After ESWT, patients with CP showed significant clinical improvement in the MAS (P = 0.011), ankle PROM (P = 0.002), walking/running/jumping function (P = 0.003), and total function (P < 0.001) of the GMFM-88. The patients with Rett syndrome showed improved MAS scores (P = 0.061) and significantly improved total gross motor function (P = 0.030). Under ARFI, patients with CP demonstrated decreased shear wave speed in the gastrocnemius medial head (P = 0.038). Conversely, patients with Rett syndrome show increased shear-wave speeds after ESWT.

Conclusion

Our study provides evidence that a weekly course of low-dose ESWT for 12 weeks is beneficial for children with both CP and Rett syndrome, with the clinical effects of reducing spasticity and improving the gross motor function of the lower limbs. The ARFI sonoelastography reveals improvement of muscle stiffness in patients with CP after ESWT, but deteriorated in patients with Rett syndrome. The diverse therapeutic response to ESWT may be caused by the MECP2 mutation in Rett syndrome, having a continuous impact and driving the pathophysiology differently as compared to CP, which is secondary to a static insult.

Trial registration IRB 201700462A3. Registered 22March 2017, https://cghhrpms.cgmh.org.tw/HRPMS/Default.aspx.
Prevalence of hospital-acquired pressure injuries in intensive care units of the Eastern Mediterranean region: a systematic review and meta-analysis
Authors: Isfahani Parvaneh , Alirezaei Samira , Samani Somayeh , Bolagh Fateme , Heydari Azadeh , Sarani Mohammad , Afshari Mahnaz
Published: January 2024

Background

Hospital-acquired pressure injuries are a major patient safety concern in intensive care units that are considered largely preventable adverse events by adherence to nursing standards of care. The hypothesis of this research was to investigate the prevalence of hospital-acquired pressure injuries in intensive care units (ICUs) of the Eastern Mediterranean Region.

Methods

This study was designed as a systematic review and meta-analysis. All articles published on Pressure ulcer prevalence in the ICUs of hospitals in Eastern Mediterranean Region countries, identified by searching PubMed through MEDLINE, Web of Science, Scopus, and Google Scholar from January 1, 2011, until September 22, 2023. The reference lists of these articles were checked for additional relevant studies. Data were analyzed using the Comprehensive Meta-Analysis Software (v.2.2.064).

Results

A total of 15 articles met the inclusion criteria. Based on the random-effects model, the overall Pressure ulcer prevalence rate was 16.6% (95% CI (8.6–29.6)). Both the highest and lowest prevalence was observed in Jordan in 2011 at 83.1% (95% CI (71.2- 90.7)) and in 2012 at 0.9% (95% CI (0.5- 1.5)), respectively. The results showed that publication year, average age, and sample size were the main causes of heterogeneity between the reviewed studies (p < 0.05).

Conclusion

This systematic review and meta-analysis of the pertinent peer-reviewed literature revealed a high prevalence of hospital-acquired pressure injuries of 16% in intensive care units of Eastern Mediterranean region. Therefore, it is necessary for health policymakers and managers in Eastern Mediterranean Region to take necessary measures to prevent the incidence of Pressure ulcers in hospitals, especially in ICUs.