bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of muscle recovery in post-ICU patients admitted for acute pancreatitis: a longitudinal single-center study
Authors: Hosse Clarissa , Beetz Nick L. , Fehrenbach Uli , Elkilany Aboelyazid , Auer Timo A. , Gebauer Bernhard , Pille Christian , Geisel Dominik , Kolck Johannes
Published: September 2024

Objectives

Critically ill patients with severe pancreatitis exhibit substantial muscle wasting, which limits in-hospital and post-hospital outcomes. Survivors of critical illness undergo extensive recovery processes. Previous studies have explored pancreatic function, quality of life, and costs post-hospitalization for AP patients, but none have comprehensively quantified muscle loss and recovery post-discharge. By applying an AI-based automated segmentation tool, we aimed to quantify muscle mass recovery in ICU patients after discharge.

Materials

Muscle segmentation was performed on 22 patients, with a minimum of three measurements taken during hospitalization and one clinically indicated examination after hospital discharge. Changes in psoas muscle area (PMA) between admission, discharge and follow up were calculated. T-Test was performed to identify significant differences between patients able and not able to recover their muscle mass.

Results

Monitoring PMA shows muscle loss during and gain after hospitalization: The mean PMA at the first scan before or at ICU admission (TP1) was 17.08 cm², at the last scan before discharge (TP2), mean PMA was 9.61 cm². The percentage change in PMA between TP1 and TP2 ranged from − 85.42% to -2.89%, with a mean change of -40.18%. The maximum muscle decay observed during the stay was − 50.61%. After a mean follow-up period of 438.73 days most patients (81%) were able to increase their muscle mass. Compared to muscle status at TP1, only 27% of patients exhibited full recovery, with the majority still presenting a deficit of 31.96%.

Conclusion

Muscle recovery in ICU patients suffering from severe AP is highly variable, with only about one third of patients recovering to their initial physical status. Opportunistic screening of post-ICU patient recovery using clinically indicated imaging and AI-based segmentation tools enables precise quantification of patients’ muscle status and can be employed to identify individuals who fail to recover and would benefit from secondary rehabilitation. Understanding the dynamics of muscle atrophy may improve prognosis and support personalized patient care.
Effect of mothers‘ health literacy on early childhood allergy prevention behaviours: results from the KUNO-Kids health study
Authors: Pawellek Maja , Köninger Angela , Melter Michael , Kabesch Michael , Apfelbacher Christian , Brandstetter Susanne ,   KUNO-Kids study group, Ambrosch Andreas , Arndt Petra A. , Baessler Andrea , Berneburg Mark , Böse-O’Reilly Stephan , Brunner Romuald , Malfertheiner Sara Fill , Franke André , Häsler Robert , Häusler Sebastian , Heid Iris , Heinze Stefanie , Högler Wolfgang , Kerzel Sebastian , Koller Michael , Leitzmann Michael , Lennon Áine , Rothfuß David , Rösch Wolfgang , Schaub Bianca , Weidinger Stephan , Wellmann Sven
Published: September 2024

Background

Parents can engage in several behaviours with regard to early childhood allergy prevention (ECAP). These can be related to diet of mother/child and the modification of the home environment; not all of them are justified by current evidence. Previous studies showed that parental health literacy (HL) is related to favourable health behaviours directed at the child. This study aimed to investigate the causal effect of mothers’ HL on ECAP behaviours and to test different moderators of this effect.

Methods

One thousand six hundred sixty-two mothers participating in the KUNO-Kids health study in the area of Regensburg, Germany were surveyed on HL (assessed via the health care scale of the Health Literacy Survey-EU questionnaire, HLS-EU-Q47) and ECAP behaviours implemented during pregnancy and the child’s first year of life. Patterns in ECAP behaviours were identified by latent class analysis. Multinomial regression modelling was performed with HL as exposure, ECAP as outcome variable, allergy risk, parental competence and bonding, anxiety and depression as moderators as well as potentially confounding variables.

Results

We identified three classes of ECAP behaviours (class 1: „breastfeeding “ N = 871; class 2: „allergen-avoidance “ N = 490; class 3: „mixed behaviours “ N = 301). In univariable as well as fully adjusted regression models, compared to class 1, class 2 was negatively, and class 3 was not associated with HL. None of the tested moderating variables altered the association between HL and ECAP significantly.

Conclusions

We found an effect of mothers’ HL on ECAP behaviours: lower HL of mothers increased allergen-avoiding behaviour directed at their child, while decreasing the chance of exclusive breastfeeding. Improving HL could contribute to the implementation of recommended ECAP behaviours in families, especially to the reduction of allergen-avoiding behaviours.
Bridging the generational gap between nurses and nurse managers: a qualitative study from Qatar
Authors: Abujaber Ahmad A. , Nashwan Abdulqadir J. , Santos Mark D. , Al-Lobaney Nabeel F. , Mathew Rejo G. , Alikutty Jamsheer P. , Kunjavara Jibin , Alomari Albara M.
Published: September 2024

Background

The nursing workforce comprises multiple generations, each with unique values, beliefs, and expectations that can influence communication, work ethic, and professional relationships. In Qatar, the generational gap between nurses and nurse managers poses challenges to effective communication and teamwork, impacting job satisfaction and patient outcomes.

Aim

This study investigates the generational gap between nurses and nurse managers in Qatar, aiming to identify strategies to enhance collaboration and create a positive work environment.

Methods

A qualitative research design was used, involving semi-structured interviews with 20 participants, including frontline nurses and senior nurse managers. Participants were purposively sampled to represent different generations. Data were collected through face-to-face and virtual interviews, then transcribed and thematically analyzed.

Findings

Four key themes emerged: Optimizing the Work Environment: Older generations preferred transformational and situational leadership, while younger nurses valued respect, teamwork, accountability, and professionalism. Strengthening Work Atmosphere through Communication and values: Older nurses favored face-to-face communication, while younger nurses preferred digital tools. Cultivating Respect and Empathy: Younger nurses emphasized fairness in assignments and promotions, while older nurses focused on empathy and understanding. Dynamic Enhancement of Healthcare Systems: Younger nurses were more adaptable to technology and professional development, while older nurses prioritized clinical care and patient outcomes.

Conclusion

The study reveals significant generational differences in leadership preferences, communication styles, and adaptability to technology. Addressing these gaps through effective leadership, ongoing education, and open communication can improve job satisfaction and patient care.
Impeding microbial biofilm formation and Pseudomonas aeruginosa virulence genes using biologically synthesized silver Carthamus nanoparticles
Authors: Abdel-Fatah Sobhy S. , Mohammad Nasser H. , Elshimy Rana. , Mosallam Farag M.
Published: September 2024

Long-term antibiotic treatment results in the increasing resistance of bacteria to antimicrobials drugs, so it is necessary to search for effective alternatives to prevent and treat pathogens that cause diseases. This study is aimed for biological synthesis of silver Carthamus nanoparticles (Ag-Carth-NPs) to combat microbial biofilm formation and Pseudomonas aeruginosa virulence genes. Ag-Carth-NPs are synthesized using Carthamus tenuis aqueous extract as environmentally friendly method has no harmful effect on environment. General factorial design is used to optimize Ag-Carth-NPs synthesis using three variables in three levels are Carthamus extract concentration, silver nitrate concentration and gamma radiation doses. Analysis of response data indicates gamma radiation has a significant effect on Ag-Carth-NPs production. Ag-Carth-NPs have sharp peak at λ max 425 nm, small and spherical particles with size 20.0 ± 1.22 nm, high stability up to 240 day with zeta potential around − 43 ± 0.12 mV, face centered cubic crystalline structure and FT-IR spectroscopy shows peak around 620 cm−1 that corresponding to AgNPs that stabilized by C. tenuis extract functional moiety. The antibacterial activity of Ag-Carth-NPs against pathogenic bacteria and fungi was determined using well diffusion method. The MIC values of Ag-Carth-NPs were (6.25, 6.25, 3.126, 25, 12.5, 12.5, 25 and 12.5 µg/ml), MBC values were (12.5, 12.5, 6.25, 50, 25, 25, 50 and 25 µg/ml) and biofilm inhibition% were (62.12, 68.25, 90.12, 69.51, 70.61, 71.12, 75.51 and 77.71%) against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Candida tropicalis and Candida albicans respectively. Ag-Carth-NPs has bactericidal efficacy and significantly reduced the swarming, swimming motility, pyocyanin and protease production of P. aeruginosa. Furthermore, P. aeruginosa ToxA gene expression was significantly down regulated by 81.5%, while exoU reduced by 78.1%, where lasR gene expression reduction was 68%, while the reduction in exoU was 66% and 60.1% decrease in lasB gene expression after treatment with Ag-Carth-NPs. This activity is attributed to effect of Ag-Carth-NPs on cell membrane integrity, down regulation of virulence gene expression, and induction of general and oxidative stress in P. aeruginosa. Ag-Carth-NPs have no significant cytotoxic effects on normal human cell (Hfb4) but have IC50 at 5.6µg/mL against of HepG-2 cells. Limitations of the study include studies with low risks of silver nanoparticles for in vitro antimicrobial effects and its toxicity.
Giving a voice to “the silent killer”: a knowledge, attitude and practice study of diabetes among French Guiana’s Parikweneh people
Authors: Rapinski Michael , Cuerrier Alain , Davy Damien
Published: September 2024

Background

The prevalence of type 2 diabetes (T2D) in the French overseas department of French Guiana, South America, nearly doubles that in its European counterpart, Metropolitan France. This region is demographically diverse and includes several populations of Indigenous Peoples. Although such populations are at particular risk of developing T2D across the Americas, very little is known about their health status in French Guiana, and accurate numbers of diabetic patients do not exist.

Methods

In light of a potential public health crisis, an ethnomedicinal study of diabetes experienced by Indigenous Parikweneh was conducted to provide better insight into the knowledge, attitudes and practices (KAP) related to this quickly emerging disease in French Guiana. Altogether, 75 interviews were conducted with community members and Elders, as well as healthcare professionals and administrators providing services to the Parikweneh population of Macouria and Saint-Georges de l’Oyapock.

Results

Interviews suggest a high incidence of T2D in this population, with cases that have risen quickly since the mid-twentieth century. Parikweneh participants linked the development of the illness to dietary changes, notably through the introduction of new and sweet foods. Recognizing the complexity of diabetes and its symptoms, diabetic patients highlighted the importance of biomedical treatments and follow-ups, though they frequently alternated or used them concomitantly with Parikweneh medicines. With the help of biomedical tools (i.e. glucometer), local medicinal practices mirrored biomedical approaches through dietary adaptation and the use of medicinal animals and plants for glycaemic control and the treatment of complications from the disease.

Conclusion

Parikweneh are appropriating T2D into their knowledge system and adapting their health system in response to this relatively new health concern. A greater understanding of local practices and perceptions relating to T2D among medical staff may therefore be beneficial for meeting patients’ needs, providing greater autonomy in their health path, and improving treatment outcomes.
Predictors for the incidence of pneumonia among HIV-infected children on antiretroviral therapy in Amhara Regional State Comprehensive Specialized Hospitals, Ethiopia: a multicenter retrospective follow-up study
Authors: Mekonnen Gebrehiwot Berie , Baye Fikadie Dagnew , Kerebeh Gashaw , Fekadie Mengistu Melak , Kassie Yohannes Tesfahun , Demile Tiruye Azene , Belay Alamirew Enyew , Belayneh Asnake Gashaw , Legesse Bruck Tesfaye , Wondie Wubet Tazeb , Messelu Mengistu Abebe
Published: September 2024

Background

Human Immune deficiency Virus (HIV) infected children are at higher risk of developing pneumonia. Particularly, in the early phase of HIV infection, the risk of acquiring pneumonia is high, and it remains a major public health problem even after the test and treatment strategy. There is no clear evidence of the overall incidence of pneumonia among HIV-infected children in Amhara region. Aimed to assess the incidence of pneumonia and its predictors among HIV-infected children receiving Antiretroviral therapy in Amhara Region Comprehensive Specialized Hospitals, 2022.

Methods

A multicenter retrospective follow-up study was conducted from June 10, 2014, to February 28, 2022, among 430 HIV-positive children receiving antiretroviral therapy. A simple random sampling technique was used. The data was taken from the national antiretroviral intake and follow-up forms. The data were collected via the KoBo toolbox and analyzed using Stata version 17. The Kaplan–Meier curve and log-rank test were employed. Bivariable and multivariable Cox regression was carried out to identify predictors of pneumonia and a P-value < 0.05 was considered significant in to multivariable analysis.

Results

A total of 407 children with a record completeness rate of 94.7% were analyzed in the study. The incidence rate of pneumonia was 4.55 (95% CI; 3.5, 5.92) per 100 person-years observation. The mean survival time was 77.67 months and the total times at risk during follow-up period were yielding 1229.33 person-year observations. Having CD4 cell count below threshold [AHR; 2.71 (95% CI: 1.37, 5.35)], WHO stage III and IV [AHR: 2.17 (95% CI: 1.15, 4.08)], ever had fair and poor treatment adherence [AHR: 2.66 (95% CI: 1.45, 4.89)], and not initiated antiretroviral therapy within seven days [AHR: 2.35 (95% CI: 1.15, 4.78)] were the positive predictors for incidence of Pneumonia.

Conclusions

In this study, the incidence of pneumonia was lower than the previous studies. CD4 cells below the threshold, ever had fair and poor adherence to antiretroviral therapy, WHO stage III and IV, and not initiated antiretroviral therapy within seven days were significant predictors. Therefore,, it is crucial to detect baseline assessment and give attention to those identified predictors promptly, and timely initiation of antiretroviral therapy need special attention.
Hemoglobin and total bilirubin may affect tacrolimus clearance in liver transplant patient following the early postoperative period: a case report
Authors: Tharanon Vichapat , Iamrahong Pansa , Tuamsem Jutamas , Choochaeam Kunvadee , Auamnoy Titinun , Sobhonslidsuk Abhasnee
Published: September 2024

Background

Tacrolimus is a potent calcineurin inhibitor (CNI) that is principally used as a first-line immunosuppressant for the prophylaxis of allograft rejection in liver transplantation (LT) patients. In clinical practice, prescribing the optimal tacrolimus dosage is complicated by its narrow therapeutic index and high pharmacokinetic variability. Thus, performing therapeutic drug monitoring (TDM) of only tacrolimus may not provide optimal drug levels. However, other influential clinical factors affecting tacrolimus levels, such as hemoglobin (Hb), hematocrit, and total bilirubin (TBIL), should be considered while adjusting tacrolimus levels. This case report aims to introduce clinicians and their teams to taking the pharmacokinetic prediction equation into consideration for a better understanding of tacrolimus dosage adjustment during the early postoperative LT.

Case presentation

In this case report, an 18-year-old male patient of Thai ethnicity was admitted for orthotropic liver transplantation, and tacrolimus was prescribed as a cornerstone immunosuppressive agent. In the immediate postoperative period, which is the most challenging period in liver transplantation, the population pharmacokinetics predictive equation was clinically used to assist in dosage adjustment of tacrolimus by considering the significant clinical factors in this case.

Hemoglobin and total bilirubin levels were deemed significant clinical factors affecting the oral clearance (CL/F) of tacrolimus. First, a decrease in the Hb concentration increases the free drug concentration and therefore increases the CL/F of tacrolimus. Second, an elevated TBIL decreases the biliary excretion of tacrolimus, resulting in a decrease in the CL/F of tacrolimus. Thus, dose optimization of tacrolimus would be accurate when taking the pharmacokinetic prediction equation into consideration. Moreover, the results may contribute to a better understanding of tacrolimus pharmacokinetic variability in each transplant patient during the immediate postoperative course.

Conclusions

Hemoglobin and total bilirubin were significant clinical factors influencing the oral clearance of tacrolimus early after liver transplantation. A decrease in the hemoglobin concentration would increase the free drug concentration and therefore increase the oral clearance of tacrolimus. An elevated total bilirubin decreases the biliary excretion of tacrolimus, resulting in a decrease in the oral clearance of tacrolimus.
Dependency-aware online task offloading based on deep reinforcement learning for IoV
Authors: Liu Chunhong , Wang Huaichen , Zhao Mengdi , Liu Jialei , Zhao Xiaoyan , Yuan Peiyan
Published: September 2024

The convergence of artificial intelligence and in-vehicle wireless communication technologies, promises to fulfill the pressing communication needs of the Internet of Vehicles (IoV) while promoting the development of vehicle applications. However, making real-time dependency-aware task offloading decisions is difficult due to the high mobility of vehicles and the dynamic nature of the network environment. This leads to additional application computation time and energy consumption, increasing the risk of offloading failures for computationally intensive and latency-sensitive applications. In this paper, an offloading strategy for vehicle applications that jointly considers latency and energy consumption in the base station cooperative computing model is proposed. Firstly, we establish a collaborative offloading model involving multiple vehicles, multiple base stations, and multiple edge servers. Transferring vehicular applications to the application queue of edge servers and prioritizing them based on their completion deadlines. Secondly, each vehicular application is modeled as a directed acyclic graph (DAG) task with data dependency relationships. Subsequently, we propose a task offloading method based on task dependency awareness in deep reinforcement learning (DAG-DQN). Tasks are assigned to edge servers at different base stations, and edge servers collaborate to process tasks, minimizing vehicle application completion time and reducing edge server energy consumption. Finally, simulation results show that compared with the heuristic method, our proposed DAG-DQN method reduces task completion time by 16%, reduces system energy consumption by 19%, and improves decision-making efficiency by 70%.
Which factors are associated with acquired weakness in the ICU? An overview of systematic reviews and meta-analyses
Authors: Fuentes-Aspe Rocío , Gutierrez-Arias Ruvistay , González-Seguel Felipe , Marzuca-Nassr Gabriel Nasri , Torres-Castro Rodrigo , Najum-Flores Jasim , Seron Pamela
Published: September 2024

Rationale

Intensive care unit-acquired weakness (ICUAW) is common in critically ill patients, characterized by muscle weakness and physical function loss. Determining risk factors for ICUAW poses challenges due to variations in assessment methods and limited generalizability of results from specific populations, the existing literature on these risk factors lacks a clear and comprehensive synthesis.

Objective

This overview aimed to synthesize risk factors for ICUAW, categorizing its modifiable and nonmodifiable factors.

Methods

An overview of systematic reviews was conducted. Six relevant databases were searched for systematic reviews. Two pairs of reviewers selected reviews following predefined criteria, where bias was evaluated. Results were qualitatively summarized and an overlap analysis was performed for meta-analyses.

Results

Eighteen systematic reviews were included, comprising 24 risk factors for ICUAW. Meta-analyses were performed for 15 factors, while remaining reviews provided qualitative syntheses. Twelve reviews had low risk of bias, 4 reviews were unclear, and 2 reviews exhibited high risk of bias. The extent of overlap ranged from 0 to 23% for the corrected covered area index. Nonmodifiable factors, including advanced age, female gender, and multiple organ failure, were consistently associated with ICUAW. Modifiable factors, including neuromuscular blocking agents, hyperglycemia, and corticosteroids, yielded conflicting results. Aminoglycosides, renal replacement therapy, and norepinephrine were associated with ICUAW but with high heterogeneity.

Conclusions

Multiple risk factors associated with ICUAW were identified, warranting consideration in prevention and treatment strategies. Some risk factors have produced conflicting results, and several remain underexplored, emphasizing the ongoing need for personalized studies encompassing all potential contributors to ICUAW development.
Exploring instructional design in K-12 STEM education: a systematic literature review
Authors: Halawa Suarman , Lin Tzu-Chiang , Hsu Ying-Shao
Published: September 2024

This study aimed to analyze articles published in the Web of Science database from 2012 to 2021 to examine the educational goals and instructional designs for STEM education. We selected articles based on the following criteria: (a) empirical research; (b) incorporating instructional design and strategies into STEM teaching; (c) including intervention; (d) focusing on K-12 education and on assessment of learning outcomes; and (e) excluding higher education and STEAM education. Based on the criteria, 229 articles were selected for coding educational goals and instructional designs for STEM education. The aspects of STEM educational goals were coded including engagement and career choice, STEM literacy, and twenty-first century competencies. The categories of instructional designs for STEM education were examined including design-based learning, inquiry-based learning, project-based learning, and problem-based learning. The results showed that engagement and career choices and STEM literacy were mainly emphasized in STEM education. Design-based learning was adopted more than inquiry-based, project-based, or problem-based learning, and this instructional design was mainly used to achieve STEM literacy. It is suggested that studies on twenty-first century competencies may require more research efforts in future STEM education research.
Extortion experiences of recent adult immigrants from Latin America: self-reported prevalence, associated costs, and current mental health
Authors: Vargas Laura , Epperson C. Neill , Richmond Therese S. , Sharif Shadi , Berkowitz Lily , Giano Zachary , Hargarten Stephen , Ungar Mark , Weigend-Vargas Eugenio , Sakai Joseph
Published: September 2024

Violence across Latin America is an increasingly important factor influencing migration to the US. A particular form of violence that is experienced by many Latinx migrants is extortion. This research analyzes the extortion experiences of Latinx immigrant adults arriving at the US southern border and the impact these experiences have on mental health. We find that on average, participants paid $804 in extortion during their migration. The most common perpetrators of extortion in our study were police followed by immigration officials throughout Latin America. Pregnant participants were less likely to experience extortion and adults traveling with children were more likely to be extorted. Participants who were extorted for money reported significantly greater severity of post-traumatic stress disorder (PTSD) symptoms compared to those who were not extorted. This research is the first of its kind to analyze extortion experiences among Latinx immigrants to the US, quantifying the prevalence, amounts paid, countries where extortion occurs, and perpetrators of extortion. In addition, extortion experiences are associated with negative effects on the mental health of newly arrived Latinx immigrants to the US. Based upon these findings, we recommend that extortion should be considered a significant stressor in the migrant experience, particularly for those adults traveling with children.
Community partnership approaches to safe sleep (CPASS) program evaluation
Authors: Lowell Gina S. , Sanford Jillian , Radecki Linda , Hanes Allison , Kozial Bonnie , Clark Felicia , McCain Jennifer , Abbasi Asim , Dalabih Sevilay , Hoffman Benjamin D. , Lee Lois K.
Published: September 2024

Background

Sudden unexpected infant death (SUID) continues to be a leading cause of death in infants in the United States (US), with significant disparities by race and socio-economic status. Infant safe sleep behaviors are associated with decreasing SUID risk, but challenges remain for families to practice these routinely. The objective of this program was to implement and evaluate a novel approach for an infant safe sleep pilot program built upon partnerships between hospitals and community-based organizations (CBOs) serving pregnant and parenting families in at-risk communities.

Methods

Community Partnership Approaches to Safe Sleep (CPASS) was a prospectively implemented infant safe sleep program. CPASS included children’s hospitals partnered with CBOs across five US cities: Portland, OR, Little Rock AR, Chicago, IL, Birmingham, AL, and Rochester, NY. The program consisted of (1) monthly learning community calls; (2) distribution of Safe Sleep Survival Kits; and (3) surveys of sites and families regarding program outcomes. Survey measures included (1) site participation in CPASS activities; (2) recipients’ use of Safe Sleep Kits; and (3) recipients’ safe sleep knowledge and behaviors.

Results

CPASS learning community activities were consistently attended by at least two representatives (1 hospital-based, 1 CBO-based) from each site. Across the five sites, 1002 safe kits were distributed over 9 months, the majority (> 85%) to families with infants ≤ 1 month old. Among participating families, 45% reported no safe sleep location before receipt of the kit. Family adherence to nighttime safe sleep recommendations included: (1) no bedsharing (M 6.0, SD 1.8, range 0–7); (2) sleep on back (M 6.3, SD 1.7, range 0–7); and (3) sleep in a crib with no blankets/toys (M 6.0, SD 2.0, range 0–7). Site interviews described how participation in CPASS influenced safe sleep conversations and incorporated local data into counseling. Hospital-CBO relationships were strengthened with program participation.

Conclusions

The CPASS pilot program provides a new, innovative model built on hospital-community partnerships for infant safe sleep promotion in SUID-impacted communities. CPASS reached families before their infant’s peak age risk for SUID and empowered families with knowledge and resources to practice infant safe sleep. Important lessons learned included improved ways to center and communicate with families.
Antimicrobial activity of compounds identified by artificial intelligence discovery engine targeting enzymes involved in Neisseria gonorrhoeae peptidoglycan metabolism
Authors: Kant Ravi , Tilford Hannah , Freitas Camila S. , Ferreira Dayana A. Santos , Ng James , Rucinski Gwennan , Watkins Joshua , Pemberton Ryan , Abramyan Tigran M. , Contreras Stephanie C. , Vera Alejandra , Christodoulides Myron
Published: September 2024

Background

Neisseria gonorrhoeae (Ng) causes the sexually transmitted disease gonorrhoea. There are no vaccines and infections are treated principally with antibiotics. However, gonococci rapidly develop resistance to every antibiotic class used and there is a need for developing new antimicrobial treatments. In this study we focused on two gonococcal enzymes as potential antimicrobial targets, namely the serine protease L,D-carboxypeptidase LdcA (NgO1274/NEIS1546) and the lytic transglycosylase LtgD (NgO0626/NEIS1212). To identify compounds that could interact with these enzymes as potential antimicrobials, we used the AtomNet virtual high-throughput screening technology. We then did a computational modelling study to examine the interactions of the most bioactive compounds with their target enzymes. The identified compounds were tested against gonococci to determine minimum inhibitory and bactericidal concentrations (MIC/MBC), specificity, and compound toxicity in vitro.

Results

AtomNet identified 74 compounds that could potentially interact with Ng-LdcA and 84 compounds that could potentially interact with Ng-LtgD. Through MIC and MBC assays, we selected the three best performing compounds for both enzymes. Compound 16 was the most active against Ng-LdcA, with a MIC50 value < 1.56 µM and MBC50/90 values between 0.195 and 0.39 µM. In general, the Ng-LdcA compounds showed higher activity than the compounds directed against Ng-LtgD, of which compound 45 had MIC50 values of 1.56–3.125 µM and MBC50/90 values between 3.125 and 6.25 µM. The compounds were specific for gonococci and did not kill other bacteria. They were also non-toxic for human conjunctival epithelial cells as judged by a resazurin assay. To support our biological data, in-depth computational modelling study detailed the interactions of the compounds with their target enzymes. Protein models were generated in silico and validated, the active binding sites and amino acids involved elucidated, and the interactions of the compounds interacting with the enzymes visualised through molecular docking and Molecular Dynamics Simulations for 50 ns and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA).

Conclusions

We have identified bioactive compounds that appear to target the N. gonorrhoeae LdcA and LtgD enzymes. By using a reductionist approach involving biological and computational data, we propose that compound Ng-LdcA-16 and Ng-LtgD-45 are promising anti-gonococcal compounds for further development.
Radiopharmaceutical small-scale preparation in Europe: will we be able to harmonize the situation?
Authors: Moya Estrella , Cerrato Celia , Bedoya Luis Miguel , Guerra José Antonio
Published: September 2024

Background

Radiopharmaceuticals have been considered a special group of medicines in Europe since 1989. The use of radiopharmaceuticals that have marketing authorization should always be the first option in clinical use, however due to their special properties the availability of approved radiopharmaceuticals is limited. For this reason, they can be produced on a small scale outside the marketing authorization process.

Main body

The in-house radiopharmaceutical preparations represent an important source of these special medicines for routine nuclear medicine practice. However, a lack of harmonization in Member States’ regulations leads to extreme differences in the use and availability of radiopharmaceuticals across Europe. The aim of this work is to provide an overview of the different national regulatory frameworks in which Directive 2001/83/UE is adopted on the preparation of radiopharmaceuticals outside the marketing authorization track in Europe. Nine different national regulations have been studied to describe how unlicensed radiopharmaceuticals are prepared. Special attention is paid to reflect the minimum standards that these preparations should meet as well as the educational requirements to be a radiopharmacist in charge of them.

Conclusion

The rapid development of new radiopharmaceuticals used in radiometabolic therapy requires a common regulation that allows balance between the use and preparation of licensed and unlicensed radiopharmaceuticals. The absence of a harmonized regulation for the radiopharmaceutical small-scale preparation and the implementation of Good Manufacture Practices, leads to extreme differences in the use, quality assurance and availability of radiopharmaceuticals in Europe.
Whether medicine supply is really meeting primary health care needs: a mixed-methods study in Shandong Province, China
Authors: Fan Zhixin , Gao Tiantian , Sun Qiang , Babar Zaheer-Ud-Din
Published: September 2024

Background

With the aging population, the increasing prevalence of chronic non-communicable diseases, and the diversified needs for primary health care (PHC) medicines, it is necessary to rethink the functional role of the supply of PHC medicines. This study aims to evaluate the supply of PHC medicines and the status of meeting PHC medicine needs.

Methods

The mixed-methods study was conducted to evaluate the supply of PHC medicines in Shandong Province. In the quantitative study, survey questionnaires were distributed to county hospitals, township hospitals, and patients, and a prescription review was performed in township hospitals. In the qualitative study, semi-structured interviews were conducted with the pharmacy managers, physicians, and patients in county hospitals, township hospitals, and village clinics. A senior pharmacist from a tertiary hospital who has rich experience on the indications for medicine use, accompanied us on a visit to inspect the PHC pharmacies to survey medicine equipment with a professional perspective.

Results

Quantitative analysis revealed that 211 county hospitals and 1,581 township hospitals participated in the survey, revealing the median annual frequency of medicine shortages of 5.0 times for county hospitals and 2.0 times for township hospitals. Of the 6,323 patient medication surveys, after excluding 152 patients not involved in medication use, 945 (15.3%) indicated medicine shortages, with half of these attributable to institutions lacking required medicines (52.8%). On average, the prescription qualified rate of 37 township hospitals was 72.2%. Four final themes emerged during the qualitative data analysis: (1) Supply of PHC medicines; (2) Solutions to the shortage of off-list medicines; (3) Appropriateness of PHC medicines list; (4) Pharmacist workforce development and pharmacy services.

Conclusions

The discrepancy between patients’ need for PHC medicine and present medicine supply is noteworthy. It is suggested that governments should optimize the existing lists to adequately meet patient medicine needs and prioritize medicines for chronic diseases, which is also particularly important for developing countries. Integrated health care may be a novel strategy to establish unified medicines list and achieve uniform pharmaceutical services in PHC.
Bacterial biodegradation of synthetic plastics: a review
Authors: Heris Yousef Sefidi
Published: September 2024

Background

Plastics are synthetic polymers that are reluctant to degradation. Therefore, their unlimited use has caused environmental problems. The reuse, reduce, and recycle methodology can solve these problems. However, this method is not efficient for mixed plastic wastes. As a result, more efficient and eco-friendly methods are necessary to remove these pollutants.

Main body of the abstract

Biodegradation is a more effective and operative method for resolving the global plastic waste problem. This method is defined as breaking down chemical compounds by the enzymes released by organisms. Bacteria are among the plastic-degrading organisms. Plastic biodegradation by bacteria occurs in four successive steps: biodeterioration, depolymerization, assimilation, and mineralization. Plastic biodegradation by these microorganisms includes different enzymatic reactions, converting synthetic plastics into simple mineral materials. These enzymes are part of metabolic pathways that use these polymers as primary substrates. Several factors, including the chemical structure of synthetic plastics, can affect their biodegradation efficacy.

Short conclusion

Although it is a promising solution for a global problem, bacterial biodegradation of synthetic plastics suffers from limitations such as slowness. The aim of the present study is to examine different aspects of bacterial biodegradation of synthetic plastics. These include the introduction of important plastic-degrading bacterial genera and enzymes involved in this biodegradation process. Additionally, metabolic pathways of synthetic plastic biodegradation, factors controlling this process, and limitations of this eco-friendly solution are examined.
On the effects of non-zero yaw on leading-edge tubercled wings
Authors: New T. H. , Mandrà S.
Published: September 2024

Steady-state numerical simulations were conducted to capture the aerodynamic characteristics and flow patterns resulting from a tubercled and non-tubercled wing subjected to various combined pitch and yaw conditions at $$Re=1.8 \times 10^{5}$$

R
e
=
1.8
×

10
5

. Pitch angle ranged from $$0^{\circ }$$

0
∘

to $$25^{\circ }$$

25
∘

, while two different yaw angles of $$10^{\circ }$$

10
∘

and $$30^{\circ }$$

30
∘

were used. Results show that $$10^{\circ }$$

10
∘

yaw angle does not impact upon the lift and drag characteristics significantly, while a $$30^{\circ }$$

30
∘

yaw angle leads to substantial lift and drag losses. Additionally, the tubercled wing continues to confer favourable stall-mitigating characteristics even for the larger yaw angle. Finally, despite skewing the flow structures significantly, the $$30^{\circ }$$

30
∘

yaw angle also reduces the formations of bi-periodic flow structures, flow separations and recirculating regions along the leading-edge tubercles, suggesting potentially better flow stability and controllability.
Food additives and contaminants in infant foods: a critical review of their health risk, trends and recent developments
Authors: Soni Swati , W. Anvil Jennifer , Kurian Christine , Chakraborty Prapti , Paari Kuppusamy Alagesan
Published: September 2024

The infant food market has expanded rapidly over the past two decades. However, the industry faces significant challenges, including concerns over the health effects of infant food additives and issues with food safety. However, new evidences suggest that certain food additives, such as those used to preserve and transport infant formula to keep it fresh for longer, should be avoided. Science into the effects of additives on human behavior makes up a sizable sector of the additives market. Problems such as hypernatremic dehydration, malnutrition, and obesity in infants are directly linked to faulty formula production. The Food and Drug Administration (FDA) has established the toxicity types and chemical tests necessary for evaluating the safety of food additives and GRAS (Generally Recognized as Safe) compounds. These tests are crucial in understanding the food safety aspects of food additives. The health effects of different types of food additives on infants are discussed in this context. The article gives an outline of various national and global agencies that provides recommendations and standards to gauge the quality of baby food. The immunological responses, allergic reaction pathways and other related health hazards among the infants and young children caused by the food additive are discussed in this article.

Graphical Abstract
The sound heritage of Kotagede: the evolving soundscape of a living museum
Authors: Mediastika Christina E. , Sudarsono Anugrah S. , Utami Sentagi S. , Setiawan Teguh , Mansell James G. , Santosa Revianto B. , Wiratama Army , Yanti Ressy J. , Cliffe Laurence
Published: September 2024

Kotagede, the capital of the ancient Mataram Kingdom and currently an area in the Yogyakarta Province of Indonesia, is known as a ‘real living museum’. It was previously a residential area with many vital premises and heritage buildings that became a tourist area. Its locally established activities enrich the visual and sound environment of the vicinity. However, it has gradually lost its distinguishing sounds. A series of studies aims to improve the possibility of restoring past soundmarks to preserve the intangible heritage and make living museums as rich as possible. This paper reports the initial stage of the series, which focuses on capturing the rich historical sounds of Kotagede. The study was carefully designed to collect comprehensive data on heritage sounds using qualitative methods consisting of an initial focus group discussion (FGD), in-depth interviews, and a final FGD. These methods resulted in a large amount of data that were processed and classified using the descriptive phenomenology approach with the Colaizzi protocol. The study found that Kotagede has various soundmarks grouped into local and outside sounds. The locally rooted sounds can be grouped into eight categories, some of which can be extended as past and present sounds and a few that have persisted from the past to the present. In the subsequent stage, this classification and local leaders' concerns helped the researchers select and prioritise sounds for preservation and tourism purposes. The study emphasises the importance of choosing suitable participants to provide detailed and comprehensive information.
Regional impairment of left ventricular longitudinal strain in aortic regurgitation
Authors: Ferreira Joana , Marta Liliana , Presume João , Freitas Pedro , Guerreiro Sara , Abecasis João , Reis Carla , Ribeiras Regina , Mendes Miguel , Andrade Maria João
Published: September 2024

Background

Aortic regurgitation (AR) has an important impact on myocardial mechanics and recent studies have proved the value of global longitudinal strain (GLS) in the assessment of its severity and prognosis. Our purpose was to assess if the direct impact of the regurgitant jet on the myocardial wall could affect regional longitudinal strain.

Methods

Eighty patients with chronic moderate/severe AR were retrospectively studied. Patients were considered to have a jet-related longitudinal strain reduction when the myocardial segments directly impacted by the jet had their longitudinal strain reduced by at least 30% compared to nonaffected segments. AR severity, left ventricular (LV) size and function were compared according to the presence/absence of this regional pattern. For those who underwent surgery, postoperative regional and global LV function was also analyzed.

Results

A pattern of regional longitudinal strain impairment was identified in 43% of patients, with a regional reduction (in median) of 10 percentage points in absolute strain values in the segments impacted by the jet, compared to nonaffected segments. In the subgroup who underwent surgery, this pattern became attenuated after surgery. Patients with regional longitudinal strain impairment were less likely to improve GLS after surgery (10% vs. 38% improved GLS by at least 2.5%, P = 0.049).

Conclusions

To our knowledge, this study identifies for the first time, a link between the location of the impact of the regurgitant jet in AR and regional longitudinal strain impairment. The presence of this regional pattern might be associated with worse postoperative LV recovery.
Design and Evaluation of Inorganic/Organic Hybrid Bio-composite for Site-Specific Oral Delivery of Darifenacin
Authors: Ishaq Wafa , Afzal Attia , Farooq Muhammad , Sarfraz Muhammad , Adnan Sherjeel , Ahmed Hammad , Waqas Muhammad , Safdar Zainab
Published: September 2024

Benign hyperplasia (BHP) is a common disorder that affects men over the age of 60 years. Transurethral resection of the prostate (TURP) is the gold standard for operative treatment, but a range of drugs are also available to improve quality of life and to reduce BHP-associated urinary tract infections and complications. Darifenacin, an anti-muscarinic agent, has been found effective for relieving symptoms of overactive bladder associated with BHP, but the drug has poor solubility and bioavailability, which are major challenges in product development. An inorganic/organic bio-composite with gastric pH-resistant property was synthesized for the targeted oral delivery of Darifenacin to the lower gastrointestinal tract (GIT). This development was accomplished through co-precipitation of calcium carbonate in quince seed-based mucilage. The FTIR, XRD, DSC, and TGA results showed good drug-polymer compatibility, and the SEM images showed calcite formation in the quince hydrogel system. After 72 h, the drug release of 34% and 75% were observed in acidic (0.1N HCl) and 6.8 pH phosphate buffer, respectively. A restricted/less drug was permeated through gastric membrane (21.8%) as compared to permeation through intestinal membrane (65%.) The developed composite showed significant reduction in testosterone-induced prostatic hyperplasia (2.39 ± 0.12***) as compared to untreated diseased animal group. No sign of organ toxicity was observed against all the developed composites. In this study, we developed an inorganic–organic composite system that is highly biocompatible and effective for targeting the lower GIT, thereby avoiding the first-pass metabolism of darifenacin.

Graphical Abstract
Presentation, Management, and Outcomes of Patients With Giant Pheochromocytoma
Authors: Bahrani Fard Bahar , Nikravangolsefid Nasrin , Maroun Justin W , Cross Ashton , Foster Trenton , McKenzie Travis J , Dy Benzon , Lyden Melanie , Young William F , Bancos Irina
Published: September 2024

Context

Data on giant pheochromocytomas (PHEOs), defined based on size 10 cm or greater, are scarce.

Objective

This work aimed to compare presentation, management, and outcomes of patients with giant vs non–giant PHEOs.

Methods

A retrospective cohort study was conducted in a referral center from 2000 to 2023. Consecutive patients with giant PHEOs and randomly chosen patients with non–giant PHEO (referents) were studied at a 1:6 ratio. Outcomes included perioperative complications, metastases, and mortality.

Results

Of 828 patients with PHEOs, 31 (3.7%) had giant PHEO (median size 12 cm, interquartile range [IQR] 10.0-13.5 cm). In comparison to referents (n = 186, median size 4 cm, IQR, 2.9-5.0 cm), patients with giant PHEO had more symptoms of catecholamine excess (median of 2 vs 1; P = .04) and presented with a higher prevalence of severe catecholamine excess (76% vs 30%; P < .0001). Adrenalectomy was performed in 94% of patients with giant PHEOs and 100% of referents. In addition to preoperative α-adrenergic blockade (89%), metyrosine was used in 14 (7%) patients, mostly in patients with giant PHEOs (26% vs 3%; P < .0001). Patients with giant PHEOs had a higher perioperative complication rate (31% vs 10%; P = .004). During a median follow-up of 3 years, metastases developed at a higher rate in patients with giant PHEOs (45% vs 4% in referents; P < .0001). Disease-specific mortality was 7% in patients with giant PHEOs and 0% in referents (P  = .02).

Conclusion

Patients with giant PHEOs compared to referents were more symptomatic, had a higher degree of catecholamine excess, and had a higher rate of perioperative complications. Almost half of patients with giant PHEOs developed metastases, warranting close follow-up.