Category: Nevin Manimala

Chem Biol Interact. 2024 Apr 5:110986. doi: 10.1016/j.cbi.2024.110986. Online ahead of print.

ABSTRACT

Snake venom metalloproteases (SVMPs) are hydrolytic enzymes dependent on metal binding, primarily zinc (Zn²⁺), at their catalytic site. They are classified into three classes (P-I to P-III). BjussuMP-II, a P-I SVMP isolated from Bothrops jararacussu snake venom, has a molecular mass of 24 kDa. It exhibits inhibitory activity on platelet aggregation and hydrolyzes fibrinogen. TNF-α upregulates the expression of adhesion molecules on endothelial cell surfaces, promoting leukocyte adhesion and migration during inflammation. Literature indicates that SVMPs may cleave the TNF-α precursor, possibly due to significant homology between metalloproteases from mammalian extracellular matrix and SVMPs. This study aimed to investigate BjussuMP-II’s effects on human umbilical vein endothelial cells (HUVEC), focusing on viability, detachment, adhesion, release, and cleavage of TNF-α, IL-1β, IL-6, IL-8, and IL-10. HUVEC were incubated with BjussuMP-II (1.5-50 μg/mL) for 3-24 h. Viability was determined using LDH release, MTT metabolization, and 7AAD for membrane integrity. Adhesion and detachment were assessed by incubating cells with BjussuMP-II and staining with Giemsa. Cytokines were quantified in HUVEC supernatants using EIA. TNF-α cleavage was evaluated using supernatants from PMA-stimulated cells or recombinant TNF-α. Results demonstrated BjussuMP-II’s proteolytic activity on casein. It was not toxic to HUVEC at any concentration or duration studied but interfered with adhesion and promoted detachment. PMA induced TNF-α release by HUVEC, but this effect was not observed with BjussuMP-II, which cleaved TNF-α. Additionally, BjussuMP-II cleaved IL-1β, IL-6, and IL-10. These findings suggest that the zinc metalloprotease BjussuMP-II could be a valuable biotechnological tool for treating inflammatory disorders involving cytokine deregulation.

PMID:38583853 | DOI:10.1016/j.cbi.2024.110986

Int J Biol Macromol. 2024 Apr 5:131441. doi: 10.1016/j.ijbiomac.2024.131441. Online ahead of print.

ABSTRACT

The thermal stability of polyurethanes, known for its limitations, was addressed in this research by seeking improvement through the introduction of carbohydrate-based chain extenders. In this research paper, we systematically sought to improve the thermal resistance of polyurethanes by incorporating carboxymethyl cellulose and chitosan, representing a pioneering application of the mixture design approach in their preparation. In this synthesis, hydroxyl-terminated polybutadiene and isophorone diisocyanate (IPDI) were reacted to prepare -NCO terminated prepolymer, which was subsequently reacted with varying mole ratios of CMC and CSN to develop a series of five PU samples. The prepared PU samples were characterized using the Fourier-transformed infrared spectroscopic technique. Thermal pyrolysis of PU samples was examined using thermal gravimetric analysis (TGA). It was observed that, among all the samples, PUS-3 showed remarkable thermal stability over a wide temperature range. A comprehensive statistical analysis was conducted to substantiate the experimental findings. It was estimated that CMC and CSN significantly enhance the thermal stability of the samples when involved in an interaction fashion. The ANOVA Table for the mixture design demonstrates that over 90 % of the total variation in thermal stability is explained by the mixture model across a wide temperature range. Moreover, PSU-3 exhibited 4 % more thermal stability over a wide range of temperatures on average, as compared to contemporary samples.

PMID:38583848 | DOI:10.1016/j.ijbiomac.2024.131441

Am J Infect Control. 2024 Apr 5:S0196-6553(24)00161-5. doi: 10.1016/j.ajic.2024.04.004. Online ahead of print.

ABSTRACT

BACKGROUND: Repeat departmental-wide surveys are commonly employed for infection-control. There remains debate concerning their cost-effectiveness.

AIM OF THE STUDY: To measure the impact of repeat departmental-wide surveys in major in-patient departments (IPD) and ambulatory facilities (AF) in a tertiary care hospital.

DESIGN: Retrospective study of 138 surveys conducted in 96 departments over a five-year period.

METHODS: Two itemized questionnaires were designed to assess the most frequently inadequately-adhered-to infection control measures: one for IPD (with 21 items), the other for AF (with 17 items).

RESULTS: A total of 72 surveys were conducted in 49 IPDs, of which 39 (54%) were repeat surveys, and 66 surveys in 47 AFs, of which 33 (50%) were repeat surveys. The baseline rate of adherence/department was 71%±14 for the IPD, with an increase from the first to the last survey to 82%±13 (p=0.037). In 15/21 measured infection control items, adherence improved. Adherence to infection control items was lower at baseline in the AFs than in the IPDs (63±27), with an increase to 76±20 (NS). Although adherence improved for nine items, it deteriorated in another eight, producing an overall statistically unchanged outcome.

CONCLUSION: Repeat whole-department surveys contribute moderately to increased adherence to infection control guidelines. Ambulatory facilities demonstrate lower rates of adherence to infection control guidelines and are less receptive to educational measures.

PMID:38583776 | DOI:10.1016/j.ajic.2024.04.004

Photodiagnosis Photodyn Ther. 2024 Apr 5:104074. doi: 10.1016/j.pdpdt.2024.104074. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate retinal thickness changes by optical coherence tomography in preobese and obese patients without hyperglycemia.

METHODS: This comparative cross-sectional study was conducted on 55 normal (18.5-24.9 kg/m2), 42 preobese (25-29.9 kg/m2), 34 obese (>30 kg/m2), a total of 131, according to body mass index (BMI) value at the time of examination. All participants were examined in the internal medicine department and fasting serological biochemical and lipid tests were performed, and those with hyperglycemia were excluded from the study. All participants underwent a full ophthalmological examination and sectoral examination of the retina with optical coherence tomography.

RESULTS: The study included 55 right eyes of 55 normal, 42 of 42 preobese, and 34 of 34 obese, age- and sex-matched participants, without hyperglycemia. The mean BMI of the normal group was 22.3 ± 1.3, 26.8 ± 1.3 in the preobese group, and 33.2 ± 4.2 in the obese group. Central foveal thickness (normal 229.8 ± 20.1 µm, preobese 234.7 ± 18.8 µm and obese 222.0 ± 23.4 µm, P:0.031) and mean inferior (normal 280.7 ± 55.8 µm, preobese 296.7 ± 11.1 µm and obese 285.3 ± 9.9 µm) thickness in the 3 mm The Early Treatment Diabetic Retinopathy Study (ETDRS) circle was significantly higher in the preobese group and significantly lower in the obese group. Mean nasal, temporal, and superior thickness in the 3 mm ETDRS circle and peripapillary retinal nerve fiber layer was higher in the preobese group and lower in the obese group but this difference was statistically not significant.

CONCLUSION: The fact that preobesity, which is not accompanied by hyperglycemia, causes an increase in the thickness of the central macular regions and obesity causes thinning of the retina, supports that lipid metabolism in the body alone can affect retinal thickness changes and retinal neurodegeneration.

PMID:38583748 | DOI:10.1016/j.pdpdt.2024.104074

Radiother Oncol. 2024 Apr 5:110270. doi: 10.1016/j.radonc.2024.110270. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Patients with Ewing Sarcoma (EWS) are treated with multimodality therapy which includes radiation therapy (RT) as an option for local control. We report on the efficacy after proton radiation therapy (PRT) to the primary site for localized and metastatic EWS.

MATERIALS AND METHODS: Forty-two children with EWS (33 localized, 9 metastatic) treated between 2007 and 2020 were enrolled on 2 prospective registry protocols for pediatric patients undergoing PRT. PRT was delivered by passive scatter (74 %), pencil-beam scanning (12 %) or mixed technique (14 %). Treated sites included the spine (45 %), pelvis/sacrum (26 %), skull/cranium (14 %), extraosseous (10 %), and chest wall (5 %). Median radiation dose was 54 Gy-RBE (range 39.6-55.8 Gy-RBE). Patients with metastatic disease received consolidative RT to metastatic sites (4 at the time of PRT to the primary site, 5 after completion of chemotherapy). Median follow-up time was 47 months after PRT.

RESULTS: The 4-year local control (LC), progression-free survival (PFS), and overall survival (OS) rates were 83 %, 71 %, and 86 %, respectively. All local failures (n = 6) were in-field failures. Tumor size ≥ 8 cm predicted for inferior 4-year LC (69 % vs 95 %, p = 0.04). 4-year PFS and OS rates were not statistically different in patients with localized versus metastatic disease (72 % vs 67 %, p = 0.70; 89 % vs 78 %, p = 0.38, respectively).

CONCLUSION: In conclusion, LC for pediatric patients with EWS treated with PRT was comparable to that of historical patients who received photon-RT. Tumor size ≥ 8 cm predicted increased risk of local failure. Patients with metastatic disease, including non-pulmonary only metastases, received radiation therapy to all metastatic sites and had favorable survival outcomes.

PMID:38583721 | DOI:10.1016/j.radonc.2024.110270

Am J Pharm Educ. 2024 Apr 5:100695. doi: 10.1016/j.ajpe.2024.100695. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the perception of students, faculty, and previous lab coaches on a near-peer teaching model integrated into a skills-based laboratory.

METHODS: As part of a longitudinal near-peer teaching experience, third professional year students are utilized as lab coaches in a skills-based laboratory course. Lab coaches deliver lectures, provide feedback, facilitate activities, and assist with class preparation spanning two semesters for first and second professional year students. Students enrolled in the courses received an anonymous 12 question survey to assess comfort and helpfulness of feedback when working with a lab coach and faculty during the 2021-2022 academic year. Statistical analysis was conducted using descriptive and inferential statistics for survey questions, and thematic analysis for open-ended responses. Semi-structured interviews of previous lab coaches and faculty were conducted, and thematic analysis was utilized for the responses.

RESULTS: The student survey had an 81.4% response rate (n=114). Students were significantly more comfortable working with and asking questions to a lab coach than a faculty instructor (mean [SD] of 4.78 [0.66] vs 4.44 [0.75]). Nine (75%) previous lab coaches, and six (43%) faculty members were also interviewed. A total of six themes regarding perceptions of the lab coach position emerged: positive impact on personal and professional development; relationship building; rewarding experience recommended to others; robust teaching experience; struggles and challenges faced by both faculty and lab coaches; appreciation of the position by faculty.

CONCLUSION: Implementing near-peer teachers into a pharmacy skills-based laboratory was very well received by students, previous lab coaches, and faculty.

PMID:38583718 | DOI:10.1016/j.ajpe.2024.100695

J Thromb Haemost. 2024 Apr 5:S1538-7836(24)00181-8. doi: 10.1016/j.jtha.2024.03.022. Online ahead of print.

ABSTRACT

BACKGROUND: Emicizumab has been approved for the prophylaxis of patients with hemophilia A with or without inhibitors. However, spontaneous and trauma-induced breakthrough bleeds have been reported in patients on emicizumab prophylaxis and no laboratory assay is validated to evaluate the hemostatic activity of emicizumab .

OBJECTIVES: The thrombin generation assay (TGA) could be a surrogate marker of the hemostatic efficacy of emicizumab. The correlation between TGA and the methods used to measure emicizumab blood concentration was evaluated in this study.

METHODS: TGA was modified by the use of a trigger reagent combining a very low concentration of tissue factor (TF) and activated factor XI (FXIa). Emicizumab quantification was performed by three methods, the modified one-step factor VIII (FVIII) assay, and two methods based on liquid chromatography and mass spectrometry (LC-MS).

RESULTS: Using TF/FXIa-triggered TGA and platelet-poor plasma, a relationship was observed between the area under the thrombin generation curve (ETP) and the clinical response of patients to emicizumab. The ultrastructure of fibrin clots was consistent with ETP results and showed that emicizumab had a hemostatic activity equivalent to 20-30 IU/dL of factor VIII. Finally, pharmacokinetic/pharmacodynamic analyses showed no correlation between ETP and LC-MS nor with modified one-stage FVIII assay, but a statistically significant correlation between the LC-MS methods and the time to peak results of TGA.

CONCLUSION: Using a modified TGA, this study showed that patients who experienced breakthrough bleeds while on emicizumab had a lower thrombin generating capacity compared to others with good clinical response to emicizumab.

PMID:38583717 | DOI:10.1016/j.jtha.2024.03.022

Am J Obstet Gynecol MFM. 2024 Apr 5:101373. doi: 10.1016/j.ajogmf.2024.101373. Online ahead of print.

ABSTRACT

BACKGROUND: In low-risk pregnancies, third trimester ultrasound examination is indicated if fundal height measurement and gestational age discrepancy is observed. Despite potential improvement in detection of ultrasound abnormality, prior trials to date on universal third trimester ultrasound examination in low-risk pregnancies, compared to indicated ultrasound examination, have not demonstrated improvement in neonatal or maternal adverse outcomes.

OBJECTIVE: The primary objective was to determine if universal third trimester ultrasound examination in low-risk pregnancies could attenuate composite neonatal adverse outcome. The secondary objectives were to compare change in composite maternal adverse outcomes and detection of abnormalities of fetal growth (fetal growth restriction or large for gestational age) or amniotic fluid (oligo- or poly-hydramnios).

STUDY DESIGN: Our pre- and post-intervention study at 9 locations included low-risk pregnancies; those without indication for ultrasound examination in the third trimester. Compared to indicated ultrasound in the pre-implementation period, in the post-implementation period all patients were scheduled for ultrasound examination at 36.0 – 37.6 weeks. In both periods clinicians intervened based on abnormalities identified. Composite neonatal adverse outcomes included any of: Apgar score ≤ 5 at 5 min, cord pH < 7.00, birth trauma (bone fracture or brachial plexus palsy), intubation for > 24 hours, hypoxic ischemic encephalopathy, seizure, sepsis (bacteremia proven with blood culture), meconium aspiration syndrome, intraventricular hemorrhage grade III or IV, periventricular leukomalacia, necrotizing enterocolitis, stillbirth after 36 weeks, or neonatal death within 28 days of birth. Composite maternal adverse outcomes included any of: chorioamnionitis, wound infection, estimated blood loss >1000mL, blood transfusion, deep venous thrombus or pulmonary embolism, admission to intensive care unit, or death. Using Bayesian statistics, we calculated a sample size of 600 individuals in each arm to detect >75% probability of any reduction in primary outcome, (80% power; 50% hypothesized risk reduction).

RESULTS: During the pre-intervention phase, 747 individuals were identified during the initial ultrasound examination and among them 568 (76.0%) met the inclusion criteria at 36.0 to 37.6 weeks; during the post-intervention period, the corresponding numbers were 770 and 661 (85.8%). The rate of identified abnormalities of fetal growth or of amniotic fluid increased from between pre- and post-intervention period (7.1% versus 22.2%, p< 0.0001; number needed to diagnose, 7; 95% confidence interval, 5-9). The primary outcome occurred in 15 of 568 (2.6%) individuals in the pre- and 12 of 661 (1.8%) in the post-intervention group (83% probability of risk reduction, posterior relative risk, 0.69; 95% credible interval, 0.34-1.42). The composite maternal adverse outcomes occurred in 8.6% in the pre- and 6.5% in post-intervention group (90% probability of risk (posterior relative risk, 0.74; 95% credible interval, 0.49-1.15). The number needed to treat to reduce composite neonatal adverse outcomes was 121 (95% confidence interval, 40-200), to reduce composite maternal adverse outcomes was 46 (95% confidence interval, 19-74), and to prevent cesarean delivery was 18 (95% confidence interval, 9-31).

CONCLUSION: Among low-risk pregnancies, compared to routine care with indicated ultrasound examination, implementation of a universal third-trimester ultrasound examination at 36.0-37.6 weeks attenuated composite neonatal and maternal adverse outcomes.

PMID:38583714 | DOI:10.1016/j.ajogmf.2024.101373

Am J Obstet Gynecol MFM. 2024 Apr 5:101374. doi: 10.1016/j.ajogmf.2024.101374. Online ahead of print.

ABSTRACT

BACKGROUND: Respiratory Distress Syndrome (RDS) is strongly associated with prematurity, including late preterm births. RDS has been shown to be associated with certain neonatal morbidities and mortality, but these associations are not well described among late preterm births.

OBJECTIVE: We sought to determine the association between RDS and adverse neonatal outcomes among late preterm (34-36 weeks) born singleton neonates.

STUDY DESIGN: This is a retrospective cohort study using California’s linked vital statistics-patient discharge data (2008-2019). We included singleton, non-anomalous births with gestational age of 34-36 weeks. Outcomes of interest were interventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), neonatal sepsis, length of hospital stay, neonatal death and infant death. Chi-square and multivariable Poisson regression analyses were used to examine the association of RDS with outcomes at each gestational age. Adjusted risk ratios (aRR) and 95% confidence intervals (CI) were estimated.

RESULTS: A total of 242,827 births were included, of which 11,312 (4.7%) had RDS. We found that among neonates with RDS, NEC was higher at 35 weeks (aRR= 3.97; 95% CI: 1.88, 8.41) and 36 weeks (aRR= 4.53; 95% CI: 1.45, 14.13). IVH, ROP, neonatal sepsis and length of hospital stay were significantly higher at 34-36 weeks’ gestation in neonates with RDS. Neonatal death was significantly higher among neonates with RDS at 35 weeks (aRR=3.04; 95% CI: 1.58, 5.85) and 36 weeks (aRR=3.25; 95% CI: 1.59, 6.68). Infant death was also significantly higher at 35 weeks (aRR=2.27; 95% CI: 1.43, 3.61) and 36 weeks (aRR=2.60; 95% CI: 1.58, 4.28).

CONCLUSION: We found that RDS was associated with IVH, ROP and sepsis at 34-36 weeks’ gestation; while RDS was associated with neonatal death, infant death and NEC at 35 and 36 weeks. Clinicians should keep these outcomes in mind when making decisions about delivery timing and the potential benefits of antenatal steroids in pregnancies in the late preterm period as well as management of RDS in late preterm neonates.

PMID:38583712 | DOI:10.1016/j.ajogmf.2024.101374

Am J Cardiol. 2024 Apr 5:S0002-9149(24)00235-2. doi: 10.1016/j.amjcard.2024.04.001. Online ahead of print.

ABSTRACT

Patients undergoing transcatheter aortic valve implantation (TAVI) commonly experience non-home discharge (NHD), a phenomenon associated with increased health-care expenditure and possibly poorer outcomes. Despite its clinical relevance in TAVI, the incidence and predictors of NHD and its impact on quality of life remain poorly characterised. Also unknown is the proportion of TAVI patients that require long-term residential care following initial NHD. Therefore, we aimed to address these questions using a large and multi-centre Australian cohort. 2229 patients undergoing TAVI from 2010-2023 included in the Alfred-Cabrini-Epworth TAVI Registry were analysed. Median age was 82 (IQR: 78-86) years and 41% were female. 257 (12%) patients were not discharged home following TAVI, with incidence falling over time (R²=0.636, p<0.001). Multivariable logistic regression modelling for NHD prediction was developed with excellent calibration and discrimination (C-Statistic 0.835). Independent predictors of NHD were post-procedural stroke (adjusted odds ratio [aOR] 11.05), procedure at a private hospital (aOR 3.01), living alone (aOR 2.35), vascular access site complications (aOR 2.09), frailty (aOR 1.89), age>80 (aOR 1.82), hypoalbuminemia (aOR 1.76), NYHA III-IV (aOR 1.74) and hospital length of stay (aOR 1.13) (all p<0.05). NHD was not associated with mortality at 30-days and less than one percent of all patients required longer-term residential care. In conclusion, while common following TAVI, NHD does not predict short-term mortality, most patients successfully return home within 30-days and when used appropriately, NHD may serve as a brief and effective method of optimising functional status without compromising long-term independence.

PMID:38583699 | DOI:10.1016/j.amjcard.2024.04.001