ChemInform Research Articles

Rapid enzymatic assay for antiretroviral drug monitoring using CRISPR-Cas12a enabled readout.

Maintaining efficacy of human immunodeficiency virus (HIV) medications is challenging among children because of dosing difficulties, the limited number of approved drugs, and low rates of medication adherence. Drug level feedback (DLF) can support dose optimization and timely interventions to prevent treatment failure, but current tests are heavily instrumented and centralized. We developed the REverse-transcriptase ACTivity-crispR (REACTR) assay for rapid measurement of HIV drugs based on the extent of DNA synthesis by HIV reverse transcriptase. CRISPR-Cas enzymes bind to synthesized DNA, triggering collateral cleavage of quenched reporters and generating fluorescence. We measured azidothymidine triphosphate (AZT-TP), a key drug in pediatric HIV treatment, and investigated the impact of assay time and DNA template length on REACTR's sensitivity. REACTR selectively measured clinically relevant AZT-TP concentrations in the presence of genomic DNA and peripheral blood mononuclear cell lysate. REACTR has the potential to enable rapid point-of-care HIV DLF to improve pediatric HIV care.

A novel blended and interprofessional approach to pediatric emergency training: self-assessment, perception, and perceived long-term effects

BackgroundWe developed a blended training program at a tertiary pediatric center based on hospital-specific emergency guidelines, profession-specific Virtual Patients (VPs), and interprofessional team training. Using this novel approach, we addressed differing educational needs of medical and nursing staff and intrinsic cognitive overload among participants, aiming for harmonization of in-house emergency proceedings.MethodsSelf-assessments of pediatric emergency knowledge and skills were conducted before (T1) and after (T2) preparation using VPs, as well as after the team training day (T3). At T3, participants completed questionnaires on the training approach, its components, and learning impact. Ten months after the training, a follow-up survey (T4) queried perceived benefits within and beyond emergency situations.ResultsA total of 56 medical staff and 56 nursing staff members participated in the pilot phase. Of these, N = 55 (98%) and N = 48 (85%), respectively, returned self-assessments; questionnaires were completed by N = 55 (98%) and N = 51 (91%), respectively. In both groups, 57 participants (50.9%) completed the follow-up survey. After team training (T3), both groups had statistically significant increased knowledge and skill scores compared with those at T1. Regarding the blended approach and its components, medical and nursing staff alike rated the entire course and its guidelines, the preparatory VPs, and the team training very highly. Participants felt being better prepared for pediatric emergencies. Perceived strengths of the training approach were in the triangulation of teaching methods and its interprofessionalism. More training scenarios were requested, as well as recurrent training. In the follow-up, participants reported improved confidence and calmness, as well as improved communication and collaboration when involved in an emergency. Beyond emergencies, benefits were reported in daily routines.ConclusionsOur blended approach was perceived as being effective in improving preparedness among medical and nursing house staff. This approach permits customization of content and deliberate practice to improve pediatric critical care.

Integrating Diagnostic Approaches in Infant Bacterial Meningitis Caused by a Non-K1 Escherichia coli: A Case Report

Background: Infant meningitis, particularly caused by Escherichia coli, remains a life-threatening condition, especially in premature and low-weight infants. Infections of the central nervous system can be fatal, necessitating prompt diagnosis and appropriate treatment. Acute infections caused by various pathogens, including E. coli, often present with similar clinical symptoms. The rapid identification of pathogens and their antimicrobial resistance mechanisms is critical for timely and effective treatment. We report the case of an 8-month-old patient who presented with fever, diarrhea, and convulsive seizures and was subsequently diagnosed with meningitis. Despite initial empirical treatment with ceftriaxone, the patient’s condition worsened. Methods: At Bambino Gesù Children’s Hospital, molecular diagnostic tools, including the FilmArray Meningitis/Encephalitis and Blood Culture Identification panels, were employed. Results: Although the Meningitis panel did not detect any pathogens due to the lack of the specific bacterial target, the off-label use of the Blood Culture Identification panel identified a non-K1 Escherichia coli strain carrying the CTX-M resistance gene, an extended-spectrum beta-lactamase (ESBL). Despite the rapid diagnostic approach and adjustment of antibiotic therapy, the patient succumbed to the infection due to the strain’s high virulence and multidrug resistance. Whole-genome sequencing further characterized the strain, revealing that it belonged to the ST131 group, a highly resistant and virulent strain associated with sepsis. Conclusions: This case highlights the importance of integrating advanced molecular diagnostics, such as whole-genome sequencing, with traditional methods to improve pathogen detection, especially in cases of emerging resistant strains that are not covered by standard diagnostic panels. It also emphasizes the need for the continuous adaptation of diagnostic tools to include non-K1 E. coli strains for more comprehensive and timely meningitis diagnosis.

Factors influencing postoperative urinary retention after radical hysterectomy for cervical cancer: development and validation of a predictive model in a prospective cohort study in Southwest China

ObjectivesTo explore influencing factors for postoperative urinary retention (POUR) in cervical cancer patients and construct and validate a POUR prediction model.DesignA prospective cohort study.SettingA large tertiary hospital specialised in child...

Prognostic impact of preoperative osteosarcopenia on esophageal cancer surgery outcomes: a retrospective analysis.

Osteosarcopenia, recognized as a consequence of aging, has garnered attention as a prognostic marker in recent years; however, its clinical significance in esophageal cancer remains uncertain. This study aimed to investigate the impact of osteosarcopenia on esophageal cancer surgery outcomes. This retrospective study included patients with advanced esophageal cancer who underwent surgical resection between 2018 and 2021. Skeletal muscle index at the L3 vertebral level and bone density at the Th11 vertebral level were measured on preoperative computed tomography scans. Based on the findings, we divided patients into sarcopenia, osteopenia, and osteosarcopenia groups, and analyzed the relationship between osteosarcopenia and clinicopathological factors, including prognosis. Of the 124 patients included, 59 (48%) were diagnosed with osteosarcopenia. Among all, 46 (37%) patients experienced postoperative recurrence, and a significant correlation was observed between osteosarcopenia and recurrence (p < 0.05). Overall survival and relapse-free survival were significantly shorter in the osteosarcopenia group than in the non-osteosarcopenia group (p < 0.05 for both). In a subgroup analysis, overall survival and relapse-free survival were significantly shorter in the osteosarcopenia group than in the non-osteosarcopenia group, or in the sarcopenia and osteopenia alone groups (all p < 0.05). The presence of preoperative osteosarcopenia was found to affect the prognosis following esophageal cancer surgery.

Structural Basis for Catalysis and Substrate Specificity of a LarA Racemase with a Broad Substrate Spectrum.

The LarA family consists of diverse racemases/epimerases that interconvert the diastereomers of a variety of α-hydroxyacids by using a nickel-pincer nucleotide (NPN) cofactor. The hidden redox reaction catalyzed by the NPN cofactor makes LarA enzymes attractive engineering targets for applications. However, how a LarA enzyme binds its natural substrate and recognizes different α-hydroxyacids has not been elucidated. Here, we report three high-resolution structures of the enzyme-substrate complexes of a broad-spectrum LarA enzyme from Isosphaera pallida (LarA Ip ). The substrate binding mode reveals an optimal orientation and distance between the hydride donor and acceptor, strongly supporting the proposed proton-coupled hydride transfer mechanism. The experimentally solved structures, together with the structural models of other LarA enzymes, allow us to identify the residues/structural elements critically involved in the interactions with different α-hydroxyacid substrates. Collectively, this work provides a critical structural basis for catalysis and substrate recognition of the diverse enzymes in the LarA family, thus building a foundation for enzyme engineering.

The Future of Pediatric Care: AI and ML as Catalysts for Change in Genetic Syndrome Management

This review explores the significant impact of Artificial Intelligence (AI) and Machine Learning (ML) on pediatric healthcare and education for children with genetic syndromes. Our investigation shows that AI-driven tools, like Google AI's DeepVariant, have greatly improved diagnostic precision. This allows for earlier and more accurate identification of genetic anomalies in conditions such as Cri-du-Chat Syndrome and 22q11.2 Deletion Syndrome. In addition, ML-based approaches have played a crucial role in advancing personalized treatment strategies, such as utilizing pharmacogenomic models to optimize drug therapies for Duchenne Muscular Dystrophy. Adaptive learning platforms, such as DreamBox Learning, have effectively tailored educational content according to the specific requirements of children with syndromes like Phelan-McDermid Syndrome. The review suggests that combining AI and ML significantly enhances diagnostic accuracy, treatment effectiveness, and educational results, thereby establishing higher benchmarks for pediatric care. Nevertheless, these advancements have notable ethical, legal, and social challenges. It is essential to prioritize equitable access, data privacy protection, and algorithmic transparency to maximize the benefits and minimize potential risks associated with AI. Overall, the findings underscore the potential of AI and ML to revolutionize pediatric genetic care, provided that these technologies are implemented responsibly and inclusively.

Prior antibiotics exposure is associated with an elevated risk of surgical site infections, including anastomotic leakage, after colon cancer but not rectal cancer surgery: A register-based study of 38,839 patients.

Gut microbiota composition has been implicated in surgical site complications after colorectal cancer surgery. Antibiotics affect gut microbiota, but evidence for a role in surgical site complications is inconclusive. We aimed to investigate use of prescription antibiotics during the years before surgery in relation to the risk of surgical site infections, including anastomotic leakage, within 30 days after surgery. Cardiovascular/neurological complications and the urinary antiseptic methenamine hippurate, for which there is no clear link with the microbiota, were used as negative controls. We conducted a patient cohort study using complete population data from Swedish national registers between 2005 and 2020. The final study population comprised 26,527 colon cancer and 12,312 rectal cancer cases with a 4.5 year exposure window. In colon cancer patients, antibiotics use was associated with a higher risk of surgical site infections (adjusted odds ratio (aOR) for any versus no use = 1.20, 95% confidence interval (CI) 1.10-1.33) and anastomotic leakage in particular (aOR =1.19, 95% CI 1.03-1.36), both with dose-response relationships for increasing cumulative antibiotics use (Ptrend = <0.001 and Ptrend = 0.047, respectively). Conversely, associations in rectal cancer patients, as well as for the negative controls cardiovascular/neurological complications and methenamine hippurate, were null. In conclusion, prescription antibiotics use up to 4.5 years before colorectal cancer surgery is associated with a higher risk of surgical site infections, including anastomotic leakage, after colon cancer but not rectal cancer surgery. These findings support a role for antibiotics-induced intestinal dysbiosis in surgical site infections.

Preventive effect of probiotics on infections following colorectal cancer surgery: An umbrella meta-analysis

BACKGROUND Postoperative infections remain a significant source of morbidity among patients undergoing colorectal cancer (CRC) surgery. While probiotics have been proposed as a potential strategy to mitigate the risk of these infections, contemporary meta-analyses have produced conflicting findings. AIM To synthesize the available evidence regarding the prophylactic efficacy of probiotics in preventing infections following CRC surgery. METHODS A comprehensive search of PubMed and Scopus was conducted to identify relevant meta-analyses published up to February 2024. To assess the efficacy of probiotics on outcomes, relative risks (RR) and their corresponding 95%CI were pooled using a random effects model. RESULTS This comprehensive umbrella meta-analysis integrated eleven meta-analyses encompassing 11518 participants who fulfilled the inclusion criteria. Probiotics administration resulted in a statistically significant reduction in the incidence of total infections (RR: 0.40, 95%CI: 0.31-0.51; moderate certainty), surgical site infections (RR: 0.56, 95%CI: 0.49-0.63; high certainty), pneumonia (RR: 0.38, 95%CI: 0.30-0.48; high certainty), urinary tract infections (RR: 0.44, 95%CI: 0.31-0.61; moderate certainty), bacteremia (RR: 0.41, 95%CI: 0.30-0.56; high certainty), and sepsis (RR: 0.35, 95%CI: 0.25-0.44; high certainty). However, probiotics did not significantly affect intra-abdominal, central line, or peritoneal infections. CONCLUSION Probiotics have demonstrated potential in mitigating postoperative infectious complications among patients undergoing CRC surgery.

Cognitive clarity in colon surgery: The dexmedetomidine advantage

Colon cancer is one of the most prevalent cancers globally, especially in the older age group. A large number of older patients undergoing surgery for colon cancer suffer from postoperative cognitive dysfunction (POCD). The trial by Bu et al demonstrated that dexmedetomidine (Dex) significantly reduced the incidence of POCD compared to placebo in individuals undergoing colon cancer surgery. Additionally, better cerebral oxygenation and lower cerebral injury markers were reported with the use of Dex. The trial has some limitations, such as a single-center design and a smaller sample size, and further studies with larger patient populations and robust multi-center designs are warranted to establish these findings.

Our experience at Bangabandhu Sheikh Mujib Medical University on laparoscopic assisted surgery for rectal cancer

Background: Rectal cancer is a leading cause of mortality worldwide, with laparoscopic surgery emerging as a viable alternative to open surgery due to its benefits in postoperative recovery, pain management and survival rates. Despite its advantages, laparoscopic colorectal resection faces scrutiny over oncologic safety and technical demands, limiting its widespread adoption. Methods: This retrospective descriptive study analyzed 60 patients with colorectal adenocarcinoma treated at the Department of Colorectal Surgery, BSMMU, from January 2018 to December 2018. Inclusion criteria encompassed clinically diagnosed colorectal cancer with histological confirmation. Data on demographics, tumor characteristics, surgical details and postoperative outcomes were collected and analyzed with SPSS software. Results: Among the 60 patients, 32 were male, with a mean age of 52 years. Tumors within 5 cm of the anal verge necessitated abdominoperineal resections (n=44), while anterior resections were performed for the remaining (n=16). All patients achieved adequate proximal margins (&gt;5 cm) and most (90%) had distal margins &gt;2 cm. The average operative time ranged from 190 to 270 minutes, with no intraoperative complications and a postoperative stay of 3-5 days. Patients reported less postoperative pain and faster recovery. Conclusions: Laparoscopic colorectal surgery demonstrated similar oncologic outcomes to open surgery but involved a longer operative time and required advanced surgical skills. The benefits included reduced blood loss, lower postoperative pain and a shorter hospital stay, although costs were higher. A need for expert surgeons in selected patients is emphasized for optimal outcomes. Laparoscopic resection for rectal cancer aligns with oncologic principles and offers a safe, effective approach, yielding improved recovery metrics compared to traditional surgery. Further analysis on cost-effectiveness, especially for lower socioeconomic populations, is warranted to enhance accessibility.

Precision Activity-Based α-Amylase Probes for Dissection and Annotation of Linear and Branched-Chain Starch-Degrading Enzymes.

α-Amylases are the workhorse enzymes of starch degradation. They are central to human health, including as targets for anti-diabetic compounds, but are also the key enzymes in the industrial processing of starch for biofuels, corn syrups, brewing and detergents. Dissection of the activity, specificity and stability of α-amylases is crucial to understanding their biology and allowing their exploitation. Yet, functional characterization lags behind DNA sequencing and genomics; and new tools are required for rapid analysis of α-amylase function. Here, we design, synthesize and apply new branched α-amylase activity-based probes. Using both α-1,6 branched and unbranched α-1,4 maltobiose activity-based probes we were able to explore the stability and substrate specificity of both a panel of human gut microbial α-amylases and a panel of industrially relevant α-amylases. We also demonstrate how we can detect and annotate the substrate specificity of α-amylases in the complex cell lysate of both a prominent gut microbe and a diverse compost sample by in-gel fluorescence and mass spectrometry. A toolbox of starch-active activity-based probes will enable rapid functional dissection of α-amylases. We envisage activity-based probes contributing to better selection and engineering of enzymes for industrial application as well as fundamental analysis of enzymes in human health.

Supplemental Oxygen on the Annie Smith Peck Expedition of 1903 to 6,367 m (20,892 ft) Mount Sorata (Illampu).

Lankford, Harvey V, Hannah Kimberley. Supplemental Oxygen on the Annie Smith Peck Expedition of 1903 to 6,367 m (20,892 ft) Mount Sorata (Illampu). High Alt Med Biol. 00:00-00, 2024. The 1903 expedition to 6,367 m (20,892 ft) Mount Sorata (Illampu) in Bolivia that was conceived, organized, and led by American mountaineer Annie Smith Peck appears to have been the first to take a supplemental oxygen apparatus to a great mountain. The expedition did not have heavy cylinders of compressed oxygen or closed-circuit rebreathers with chemically generated oxygen but took an apparatus to produce oxygen on the mountain apparently by a 19th century heated chlorate chemical method. Oxygen was to be manufactured in camp, stored in rubber bags, and used with an open-circuit breathing set while climbing. The equipment was taken, but once in Bolivia, a late change in plans resulted in a summit attempt on 6,427 m (21,086 ft) Ancohuma rather than Illampu on the twin-peaked Sorata massif. The summit attempt ended prematurely at 4,700 m (15,350 ft), and the oxygen system was not used. The present paper reviews some of the supplemental oxygen options that were available in 1903 and examines the Sorata expedition, a little-known part of the early history of mountaineering oxygen use.

Reconsidering the Need for Intraoperative Frozen Section in Sentinel Lymph Node Biopsy for Early Breast Cancer in Bahrain.

Frozen section is performed in sentinel lymph node biopsy (SLNB) for early breast cancer to prevent a second surgery, but it has certain disadvantages. Several trials have demonstrated the oncological safety of avoiding axillary dissection in patients with 1-2 positive nodes. This study aimed to assess the need for frozen section during SLNB in early breast cancer. This retrospective study included patients with early-stage clinically node-negative breast cancer who underwent SLNB with frozen section at Salmaniya Medical Complex, Manama, Bahrain, between October 2021 and September 2023. Patients who had neoadjuvant chemotherapy, cT3-4 tumours, ductal carcinoma in situ, occult breast cancer and previous breast cancer were excluded. A total of 147 patients underwent breast cancer surgery with SLNB using frozen section. The sensitivity of frozen section was 84.6%, and the false-negative rate was 15.4%. Furthermore, 4.8% underwent immediate axillary dissection. In the remaining cases, there were only 1-2 positive sentinel nodes, and axillary dissection was omitted. Multifocal or multicentric disease was significantly associated with <3 positive sentinel nodes (71.4% versus 15.0%; P = 0.005). Patients with an indication for axillary dissection were also more likely to have tumours with lymphovascular invasion compared to patients with ≥3 positive sentinel nodes (85.7% versus 17.1%; P = 0.001). There was no indication for frozen section is needed in most patients with early breast cancer. Routine frozen section is unnecessary during SLNB, and permanent section alone may be sufficient without compromising overall standard of care.

Low Skeletal Muscle Mass: A Strong Predictive Factor for Surgical Complications After Free Forearm Flap Reconstruction in Oral Cancer Patients.

Low skeletal muscle mass (SMM) is a predictive factor for complications in patients undergoing major head and neck cancer surgery. This study aims to identify the predictive value of low SMM for postoperative complications in patients who underwent free forearm flap (FAFF) reconstructions after oral cancer resections. A retrospective study was performed with all patients who underwent FFAF between 2003 and 2020 for an oral cavity reconstruction after cancer ablation. Free flap related, any postoperative complications and hospital stay were investigated. Low SMM was associated with an increased risk of free flap associated complications (OR 2.14; 95% CI 1.02-4.39, p = 0.029). Low SMM was associated with severe complications (Clavien-Dindo ≥ III) (OR 1.46; 95% CI 1.20-2.09, p = 0.02). Low SMM is a strong predictive factor for free flap related surgical complications in patients undergoing FAFF reconstruction after resection of oral cancer.

Safety of ipsilateral intravenous access in breast cancer surgery patients

A clinical decision report appraising: Naranjo J, Portner ER, Jakub JW, Cheville AL, Nuttall GA. Ipsilateral Intravenous Catheter Placement in Breast Cancer Surgery Patients. Anesth Analg. 2021 Sep 1;133(3):707-712. https://doi.org/10.1213/ANE.0000000000005597 for a post-lumpectomy patient requiring ipsilateral peripherally inserted central catheter.

Nationwide medical database study for postoperative nutritional management in patients undergoing gastroenterological cancer surgery

Nationwide medical database study for postoperative nutritional management in patients undergoing gastroenterological cancer surgery

Qualitative study of paediatricians’ experiences in the care process for preschool children with complex needs: an example of paediatric care in Croatia

ObjectivesPreschool children with complex needs require a multidimensional care model. In such a model, paediatricians are one of the key stakeholders. This study examines Croatian paediatricians’ experiences and perceptions of...

Nutrition-Focused Quality Improvement Programs in Pediatric Care

Nutrition is fundamental to a child’s growth and development. However, nutritional health is often compromised by acute and chronic conditions and treatments that can commonly result in malnutrition. Malnutrition encompasses undernutrition and overnutrition and may be exacerbated by food insecurity. Recent health policy efforts in the United States (US) include those focused on quality measurement and social determinants of health (SDOH) to reduce risks for malnutrition and food insecurity. Nutrition-focused quality improvement programs (QIPs) have emerged as a successful model for benchmarking current nutrition care in adult patients and creating pathways for establishing best practices for timely malnutrition screening, intervention, and appropriate follow-up and care coordination. However, less is known about opportunities for nutrition-focused QIPs in hospital pediatric malnutrition care. This Perspective helps fill the gap by discussing the problem of pediatric malnutrition and current US quality frameworks and child nutrition programs related to malnutrition and food insecurity. In addition, this Perspective summarizes how nutrition-focused QIPs can impact malnutrition, including how QIPs can link hospital care with patient discharge planning and outpatient interventions. Finally, the Perspective outlines specific opportunities for the implementation of pediatric nutrition-focused QIPs to reduce office visits and/or inpatient readmissions through appropriate nutrition screening, assessment, and interventions.

Reporting of Search Strategy Among Systematic Reviews in Leading Dental Specialty Journals: A Research-On-Research Study.

Literature searching is one of the main determinants of a systematic review (SR)'s reliability. Thus, adequate reporting of search strategy is essential for the critical appraisal of SRs and evidence-based practice. To assess the reporting quality of search strategy among SRs in leading dental specialty journals, and to identify factors associated with quality of reporting. Six leading dental journals with the highest 5-year impact factors in their respective specialty were included. A hand search was undertaken to identify SRs published between 2017 and 2022. Full texts were reviewed by two authors to identify eligible SRs. Reporting quality was assessed and scored using a modified 15-item checklist based on Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension (PRISMA-S). Univariable and multivariable linear regression analyses were then performed. A total of 152 reviews were included and assessed. As for information sources, only 'citation searching' was adequately reported in most reviews 110 (72.4%). Only 23 (15.1%) of the included reviews clearly reported search strategies. Information about peer review was provided in only 10 reviews (6.6%). Only 91 (59.9%) of the included reviews documented the total records clearly. According to multivariable regression analysis, industrial funding (p = 0.012), registration (p = 0.013) and librarian involvement (p = 0.004) were significantly associated with higher reporting quality. The reporting quality of search strategy among SRs in leading dental specialty journals is suboptimal. Researchers, librarians, reviewers and journal editors in dentistry need to be familiar with the PRISMA-S checklist, and make concerted efforts to improve the reporting of search strategy in SRs.