Nevin Manimala

ACS Synth Biol. 2026 Feb 8. doi: 10.1021/acssynbio.5c00650. Online ahead of print.

ABSTRACT

Whole-cell biosensors are powerful tools for metabolite monitoring, yet challenges such as narrow dynamic range and high leaky expression limit their broader applications. Here, we present a systematic workflow based on two Design-Build-Test-Learn (DBTL) cycles to develop and optimize a transcription factor-based pyruvate biosensor in Escherichia coli. In the first iteration of the cycle, we constructed a biosensor that responded to intracellular pyruvate levels within the 0.05-10 mM range. In the second cycle, we implemented the design of experiments (DoE) to systematically explore combinatorial effects of promoters and ribosome-binding sites (RBSs). A first set of experiments was designed to identify factors with a significant effect on biosensor performance. The results showed that the RBS of the reporter gene significantly influenced the dynamic range by modulating basal and maximum expression, while the RBS of the transcription factor affected the signal span. The Akaike Information Criterion was used to select a model incorporating two main effects and one interaction effect. The best-performing strain exhibited an 18.54-fold increase in the dynamic range and a 37.22-fold reduction in leaky expression. Quantification of intracellular pyruvate confirmed an operational range of 1.23-6.81 μmol/g DCW. Our work demonstrates the power of DBTL cycles with statistical modeling for biosensor engineering, offering potential applications in precise metabolic regulation and screening applications.

PMID:41655136 | DOI:10.1021/acssynbio.5c00650

Inflamm Bowel Dis. 2026 Feb 8:izaf333. doi: 10.1093/ibd/izaf333. Online ahead of print.

ABSTRACT

INTRODUCTION: Rapid symptom relief is an important consideration for patients with ulcerative colitis (UC) experiencing a flare. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active UC. We evaluated patient-reported symptomatic improvement from patients in the ELEVATE UC program.

METHODS: This study was a post-hoc analysis of pooled daily e-diary data from patients with moderately to severely active UC receiving etrasimod or placebo in the phase III ELEVATE UC 52 and ELEVATE UC 12 trials. During the 12-week induction periods, patients self-reported stool frequency and rectal bleeding on days 1-28. Daily symptomatic response and symptomatic remission were calculated (partial modified Mayo Score).

RESULTS: Overall, 787 patients (527 receiving etrasimod, 260 placebo) were included in the analysis. Etrasimod-treated patients had statistically significantly higher rates of symptomatic response and symptomatic remission during the first 28 days of therapy, with adjusted differences (95% CIs) reaching statistical significance from day 2 (5.6% [0.8-10.3], P = .022) to day 11 (4.7% [0.4-9.0], P = .034), respectively. In patients naïve to biologic/Janus kinase inhibitor therapy, symptomatic response was statistically significantly improved with etrasimod vs placebo from day 3 (8.9% [2.3-15.5], P = .008). Symptomatic improvement rates were similar with and without concomitant corticosteroid use.

CONCLUSIONS: In this post-hoc analysis, improvements in UC symptoms occurred in patients receiving etrasimod vs placebo from as early as day 2. These findings indicate a rapid onset of symptomatic effect with etrasimod treatment for moderately to severely active UC.

CLINICALTRIALS.GOV NUMBERS: NCT03945188, NCT03996369.

PMID:41655066 | DOI:10.1093/ibd/izaf333

Int J Neurosci. 2026 Feb 7:1-21. doi: 10.1080/00207454.2026.2628832. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the safety and efficacy of Edaravone-Dexborneol as a neuroprotective agent in patients with acute ischemic stroke (AIS).

METHODS: We conducted a comprehensive search in PubMed, Scopus, Web of Science, and Cochrane CENTRAL until January 22, 2026, including clinical trials and observational studies comparing Edaravone-Dexborneol with Edaravone monotherapy, standard treatment, and placebo. Data on functional recovery (Modified Rankin Scale [mRS], National Institutes of Health Stroke Scale [NIHSS], Barthel Index [BI]), safety outcomes, and mortality were extracted. A random effects model was used for statistical analysis.

RESULTS: Overall, 13 studies (5 cohort studies and 8 randomized controlled trials) involving 7,846 patients were included, demonstrating that Edaravone-Dexborneol significantly improved 90-day mRS scores (0-1) compared with Edaravone alone (RD: 0.08, 95% CI: [0.03, 0.13], P = 0.001). When compared with standard treatment, NIHSS scores were significantly lower in the Edaravone-Dexborneol group (MD: -2.18, 95% CI: [-3.75, -0.62], P = 0.006), and no significant difference was observed in mRS (0-1) or the risk of symptomatic intracranial hemorrhage (sICH). Safety outcomes showed a possible dose-dependent adverse event (AE), including hyperhomocysteinemia and hypokalemia.

CONCLUSION: Edaravone-Dexborneol might be an effective treatment for improving functional recovery in patients with AIS and appears to have a relatively favorable safety profile. However, careful dosing is necessary to minimize AEs. Future research should focus on large-scale trials, long-term outcomes, and mechanistic studies to optimize treatment protocols.

PMID:41655025 | DOI:10.1080/00207454.2026.2628832

Inquiry. 2026 Jan-Dec;63:469580261418128. doi: 10.1177/00469580261418128. Epub 2026 Feb 7.

ABSTRACT

Violence during pregnancy is a significant public health concern, which is associated with different psychological consequences-including depression and suicidal ideation. Although several qualitative studies have been conducted, limited data are available on its prevalence during pregnancy and associated depression and suicidal ideation in Bangladesh. This study identifies the prevalence of violence against pregnant women and depression and suicidal ideation among affected individuals in rural Bangladesh. Our study is a secondary analysis of cross-sectional data, collected in a rural southern subdistrict in Bangladesh using the Edinburgh Postnatal Depression Scale (EPDS). The prevalence of domestic violence (DV), lifetime intimate partner violence (IPV), and IPV during pregnancy were 5.9% (n = 21; 95% CI: 3.7-8.9), 5.4% (n = 19; 95% CI: 3.3-8.3), and 9.9% (n = 35; 95% CI: 7.0-13.5), respectively. Among women exposed to DV, 66.7% (n = 14; 95% CI: 42.6-84.3) reported antenatal depression. Similarly, 68.4% (n = 13; 95% CI: 42.7-86.3) of those with a history of lifetime IPV and 42.9% (n = 15; 95% CI: 27.1-60.3) of those experiencing IPV during pregnancy had depressive symptoms. Suicidal ideation was present in 14.3% (n = 3; 95% CI: 4.2-38.7) of DV victims, 5.3% (n = 1; 95% CI: 0.6-33.8) of lifetime IPV victims, and 5.7% (n = 2; 95% CI: 1.3-21.4) of those experiencing IPV during their current pregnancies. The concerning prevalence of violence and associated mental health issues during pregnancy demands urgent targeted interventions, including policy reforms, health education, and community awareness initiatives.

PMID:41655023 | DOI:10.1177/00469580261418128

Nurs Crit Care. 2026 Mar;31(2):e70378. doi: 10.1111/nicc.70378.

ABSTRACT

BACKGROUND: Arterial blood gas (ABG) testing is a common investigation in critical care; however, evidence suggests that 33%-66% of samples may be taken without a clear clinical indication. Unnecessary testing increases costs, contributes to iatrogenic anaemia and wastes staff time. It also carries an environmental burden through resource use, waste generation and associated carbon emissions.

AIM: To evaluate the impact of an education- and guideline-based intervention on reducing clinically inappropriate ABG testing in a UK Intensive Care Unit (ICU) and to perform a triple bottom line assessment.

STUDY DESIGN: A pre- and post-quality improvement project in a 23-bed level III ICU. Baseline audit data were collected on ABG indications and appropriateness. A locally developed ABG guideline was introduced, supported by targeted bedside teaching and reinforced through visible prompts. Post-intervention audit mirrored baseline methods. This quality improvement project was underpinned by the Sustainability in Quality Improvement (SusQI) framework, which integrates environmental, financial and social sustainability principles into traditional plan, do, study and act (PDSA) methodology.

RESULTS: The total number of ABG tests decreased from 7348 to 4819, representing a 34.4% reduction. The mean ABGs per patient decreased from 14.27 to 11.78 (rate ratio, 0.826; 95% CI, 0.796-0.856; p < 0.001). The proportion of inappropriate ABGs declined from 27.0% to 4.1% (absolute risk reduction 22.9%, NNT = 4.4, p < 0.001). Post-intervention savings included £2781.90 in direct costs, 210.8 h of clinician time, 1.396 L of patient blood and 124.0 kg CO₂e emissions. No adverse impact on patient care was identified.

CONCLUSIONS: A low-cost, nurse-engaged intervention reduced unnecessary ABG testing without compromising safety, delivering quantifiable financial, operational and environmental benefits. Incorporating sustainability metrics strengthens the case for change and aligns with the NHS Net Zero agenda.

RELEVANCE TO CLINICAL PRACTICE: Critical care nurses play a central role in ABG stewardship. Equipping them with clear guidelines, education and visible prompts can rapidly change practice, improving patient safety, reducing waste and supporting sustainable healthcare delivery.

PMID:41655004 | DOI:10.1111/nicc.70378

Nurs Crit Care. 2026 Mar;31(2):e70383. doi: 10.1111/nicc.70383.

ABSTRACT

BACKGROUND: The length of stay (LOS) in critical care units greatly influences patient outcomes, nursing responsibilities and resource use.

AIM: This study aimed to identify the average LOS among CABG patients and the factors associated with LOS among CABG patients in critical care units in Jordan.

STUDY DESIGN: A prospective observational study was conducted across nine Jordanian medical centres between January and July 2023. The study sample was selected through convenience sampling. Data regarding demographics, clinical characteristics, and pre-, intra- and postoperative factors were gathered using a validated questionnaire and medical records.

RESULTS: This study recruited 172 patients undergoing CABG. The average age of participants was 57.86 years (SD ±9.5). The most common comorbidities were hypertension (73.3%) and hyperlipidaemia (69.2%), while the most frequent postoperative complication was electrolyte imbalance (42.4%). The average length of stay (LOS) was 3.8 days (SD ±2). Key factors predicting an increased LOS included acute kidney injury (β = 4.7, p = 0.002), atrial fibrillation (β = 1.82, p < 0.05), bleeding (β = 1.35, p < 0.05) and long chest tube duration (β = 2.78, p < 0.05). In contrast, intraoperative fresh frozen plasma transfusion (β = -1.68, p = 0.050) and treatment in private hospitals (β = -2.5, p = 0.010) were associated with reduced LOS.

CONCLUSION: Identifying the predictors of LOS is crucial for critical care nursing to improve patient management and facilitate recovery. Targeted nursing actions to address complications and minimise delays can enhance outcomes, shorten LOS and lessen the burden on resources in critical care settings.

RELEVANCE TO CLINICAL PRACTICE: Our study highlighted the lack of standardised, evidence-based CABG management protocols. Hence, health policymakers, healthcare professionals and nursing leaders are invited to develop practical guidelines that may enhance both patient outcomes and nursing efficiency in critical care settings. Additionally, this study identified fresh frozen plasma (FFP) transfusion as a key factor in reducing the length of stay. Thus, optimising transfusion protocols may enhance recovery, minimise complications, streamline nursing workflows, reduce the ICU burden and improve overall care delivery.

PMID:41655002 | DOI:10.1111/nicc.70383

Nurs Crit Care. 2026 Mar;31(2):e70373. doi: 10.1111/nicc.70373.

ABSTRACT

BACKGROUND: Healthcare systems increasingly adopt medical technologies in direct patient care, particularly in highly technological environments like intensive care units (ICUs). While these technologies aim to enhance clinical outcomes, they can also introduce complexities that affect healthcare professionals’ workload. Measuring workload related to the use of medical technology is crucial to ensure technologies support rather than hinder care delivery. Workload in this context encompasses temporal demands, subtask frequency and cognitive demands-distinct from scoring systems determining staffing ratios.

AIM: To identify methods and instruments to measure ICU healthcare professionals’ workload during direct patient care activities involving medical technology.

STUDY DESIGN: We will follow the Joanna Briggs Institute framework and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines, using narrative synthesis to summarise findings. Electronic databases MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Library, ISI Web of Science, the WHO International Clinical Trials Registry Platform and Google Scholar will be searched for studies published 2010-2025 reporting primary data.

EXCLUSION CRITERIA: paediatric population, editorials, letters and patient-based scoring systems (e.g., Therapeutic Intervention Scoring System-76; Nursing Activities Score). Two reviewers will independently screen records and extract data using standardised forms. Reporting quality will be assessed using a self-developed tool. Findings will be presented in a flowchart, tables and figures.

RELEVANCE TO CLINICAL PRACTICE: This review will provide a comprehensive overview of workload measurement methods during direct patient care activities involving medical technology in ICUs, serving as a practical resource for evaluating the workload impact of existing and emerging technologies.

REVIEW REGISTRATION: Open Science Framework, registered on 26th of September 2024 (registration DOI: 10.17605/OSF.IO/2A97J, https://osf.io/2a97j/).

PMID:41654999 | DOI:10.1111/nicc.70373

J Anesth Analg Crit Care. 2026 Feb 7. doi: 10.1186/s44158-026-00351-5. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The incidence of diaphragmatic-palsy following interscalene brachial plexus block (IBPB) is almost 100% where the drug volume plays a significant role. We compared the incidence of hemidiaphragmatic paresis and the success rate following IBPB using three different volumes of local anaesthetics.

METHODS: Ninety patients undergoing shoulder and arm surgeries under ultrasound-guided IBPB were randomly allocated into three groups: Group A (10 ml), Group B (15 ml), and Group C (20 ml). The drug administered was 0.75% ropivacaine with 50 mcg dexmedetomidine. The diaphragm excursion was measured before and 30 min after the block on the side of surgery. The incidence of diaphragmatic palsy and its severity were noted. The success rate following block, the onset of sensory blockade, duration of postoperative analgesia, and adverse effects were observed in all three groups. The statistical analysis was done using SPSS software.

RESULTS: The demographic data, duration of surgery, and success rate following block were statistically insignificant. The hemidiaphragmatic paresis (< 25%, 25-75%, > 75%) in Group A (29,1,0), Group B (17,13,0), and Group C (15,8,7) was statistically significant (P value < 0.001). The onset of sensory blockade was Group A (7.06 ± 0.73 min), Group B (6.23 ± 0.72 min), and Group C (4.61 ± 0.63 min) with a P value < 0.001. The duration of postoperative analgesia in Group A (440 ± 48.42 min), Group B (429 ± 44.48 min), and Group C (411 ± 51.37 min) was statistically insignificant (P value-0.072). Five patients in Group C developed hoarseness of voice postoperatively, which was managed conservatively.

CONCLUSION: Low volume ultrasound guided interscalene block (10 ml) is associated with a lower incidence of hemidiaphragmatic paresis with a similar success rate and duration of postoperative analgesia. Higher volume of the drug yields a faster onset of the sensory blockade.

PMID:41654981 | DOI:10.1186/s44158-026-00351-5

Eur J Med Res. 2026 Feb 7. doi: 10.1186/s40001-026-04012-9. Online ahead of print.

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication in the intensive care unit (ICU), and continuous renal replacement therapy (CRRT) is an important treatment option. However, there is no clear standard for the optimal time to stop CRRT. The cardiorenal interaction effect suggests that there may be a potential link between cardiac function and CRRT. This study aimed to investigate the left ventricular diastolic function for predicting CRRT discontinuation.

METHODS: This is a prospective cohort study.

RESULTS: The study included 154 AKI patients admitted to ICUs undergoing CRRT from February 2023 to August 2024, which were divided into the successful downtime group (87 patients) and the failure group (67 patients), and their baseline data, laboratory indices, and ultrasound parameters were analyzed. The results showed that serum creatinine, urea nitrogen, and E/e’ measured at the time of CRRT discontinuation were significantly lower in the successful group than in the unsuccessful group (all P < 0.05). A higher E/e’ measured at the time of CRRT discontinuation was associated with a lower likelihood of successful CRRT discontinuation (OR 0.71, 95% CI 0.61-0.83). Receiver operating characteristic analysis showed that E/e’ at the time of CRRT discontinuation had good discriminative ability for successful discontinuation (AUC 0.832), with an empirically derived cut-off value of 8.62.

CONCLUSION: Our findings suggest that left ventricular diastolic function is associated with successful CRRT discontinuation in patients with AKI, and that E/e’ may serve as a supportive, noninvasive parameter to complement clinical assessment at the time of CRRT discontinuation.

PMID:41654977 | DOI:10.1186/s40001-026-04012-9

Confl Health. 2026 Feb 7. doi: 10.1186/s13031-026-00761-w. Online ahead of print.

ABSTRACT

BACKGROUND: Armed conflict in Yemen has led to severe physical disabilities and profound psychological distress among survivors. Understanding how social support and psychological security interact to protect mental well-being is crucial for post-conflict rehabilitation. Therefore this study aimed to assess the levels and prevalence of post-traumatic stress disorder (PTSD), perceived social support, and psychological security among individuals with war-related disabilities in Yemen, and to examine the mediating role of psychological security in the relationship between social support and PTSD.

METHOD: A cross-sectional study was conducted at a rehabilitation center in Taiz City from January to September 2025. Participants (n = 117) with conflict-related physical disabilities completed the Multidimensional Scale of Perceived Social Support (MSPSS), the Psychological Security Scale (PSS), and the PTSD Checklist for DSM-5 (PCL-5). Mediation analysis was performed using the PROCESS macro.

RESULTS: The probable PTSD prevalence was 29.9% (95% CI 22.4%-38.7%). Perceived social support had a significant indirect effect on PTSD symptoms through psychological security (p < 0.05), but no significant direct effect. Psychological security statistically mediated the association between perceived social support and PTSD symptoms.

CONCLUSION: Psychological security may play a crucial role in the association between perceived social support and PTSD symptoms among war-disabled individuals. Rehabilitation programs should prioritize interventions that enhance both social support networks and psychological security to reduce PTSD symptoms.

PMID:41654968 | DOI:10.1186/s13031-026-00761-w