Blood-Brain Barrier Disruption for the Treatment of Primary Brain Tumors: Advances in the Past Half-Decade.

PURPOSE OF REVIEW: To review relevant advances in the past half-decade in the treatment of primary brain tumors via modification of blood-brain barrier (BBB) permeability. RECENT FINDINGS: BBB disruption is becoming increasingly common in the treatment of primary brain tumors. Use of mannitol in BBB disruption for targeted delivery of chemotherapeutics via superselective intra-arterial cerebral infusion (SIACI) is the most utilized strategy to modify the BBB. Mannitol is used in conjunction with chemotherapeutics, oligonucleotides, and other active agents. Convection-enhanced delivery has become an attractive option for therapeutic delivery while bypassing the BBB. Other technologic innovations include laser interstitial thermal therapy (LITT) and focused ultrasound (FUS) which have emerged as prime modalities to directly target tumors and cause significant local BBB disruption. In the past 5 years, interest has significantly increased in studying modalities to disrupt the BBB in primary brain tumors to enhance treatment responses and improve clinical outcomes.

Stability Indicating RP-HPLC-DAD method for simultaneous estimation of tadalafil and macitentan in synthetic mixture for treatment of pulmonary arterial hypertension.

OBJECTIVE: High Performance liquid chromatography is an integral analytical tool in assessing drug product stability. A simple, selective, precise, accurate and stability indicating RP-HPLC method was developed and validated for analysis of Tadalafil and Macitentan in synthetic mixture. MATERIAL AND METHOD: Chromatographic separation was performed using Phenomex Gemini C18 (25cm×4.6nm, 5µm) Column. The mobile phase consists of (10mM Ammonium Acetate in water and [Methanol: ACN 20: 80% v/v]) (40: 60% v/v). The flow rate was set to be 1.0mL/min. The injection volume was 10.00µL. The detection was carried out at 260nm at column temperature 35°C. RESULTS: The method was validating according to ICH Q2R1 guideline for accuracy, precision, reproducibility, specificity, robustness and detection and quantification limits. Stability testing was performed on Tadalafil and Macitentan and it was found that these degraded sufficiently in all applied chemical and physical conditions. Linearity for Tadalafil and Macitentan was observed 0.4-100µg/mL and 0.1-25µg/mL with correlation coefficient at 0.9999. LOD and LOQ 0.008µg/mL and 0.024µg/mL and 0.001µg/mL and 0.0029µg/mL for Tadalafil and Macitentan respectively. CONCLUSION: The developed RP-HPLC method was found to be suitable for the determination of both the drugs.

Factors affecting consumer attitudes to fungi-based protein: A pilot study.

Meat substitutes using alternative proteins can facilitate sustainable diets without compromising animal welfare. The fungal protein, also called mycoprotein is the biomass that results from the fermentation of a filamentous fungus. This paper reports the results of a consumer acceptance study of fungal protein-based meat substitutes using a mixed-method design with a web-based survey and a series of semi-structured interviews amongst European participants. Based on the description provided in the survey, 56% of participants were not directly familiar with fungal proteins but they understood its potential societal benefits. The overall Food Technology Neophobia Score (FTNS) of the sample was moderate (M = 40.0, range = 19-62), with more neophilic participants (52.9%) than neophobic (47.1%). FTN was a significant but weak predictor of Perceived Benefits (PB) and Purchase Intentions (PI). Younger participants perceived fungal proteins more positively, and city-dwellers had higher PI than rural dwellers. Reducetarians were more likely to purchase fungal proteins, compared to unrestricted omnivores. Participants with lower acceptance of fungal proteins' association with mould had significantly lower PI than those who were comfortable with it. In turn, familiarity with fungal protein was positively associated with mould acceptance. The qualitative data suggested that the sensory attributes were the most important factor in the acceptance of meat substitutes. The participants also valued clean label products which were perceived as healthier. Familiarity with other products containing mould seemed to assuage concerns and drive acceptance of fungal protein. The findings suggest that the overall acceptance of fungal protein is still rather low. This may be attributed to the perceived low appeal and tastiness of available fungal protein products.

A Multidimensional Examination of the Measurement of Treatment Engagement: Implications for Children's Mental Health Services and Research.

OBJECTIVE: The gap between rates of children's mental health problems and their participation in services highlights the need to address concerns related to engagement in mental health services more effectively. To identify, understand, and resolve engagement concerns appropriately requires effective measurement. In this study, we employed a multidimensional conceptual framework of engagement to examine the measurement of engagement in intervention studies focused on improving children's and/or families' engagement in services. METHOD: We coded 52 randomized controlled trials (RCTs) of interventions designed to enhance treatment engagement published between 1974 and 2019 to examine what engagement constructs have been measured, how these constructs have been measured, who has provided information about engagement, and when and why engagement measures have been administered. RESULTS: Attendance was measured in 94.2% of studies, and 59.6% of studies measured only attendance. Furthermore, most studies (61.5%) measured only one engagement dimension. One hundred twelve unique indicators of treatment engagement were used (61.6% measuring attendance). Infrequent measurement of youth (19.2% of studies) or caregiver (26.9%) perspectives was apparent. About half (54.7%) of measures were completed on one occasion, with 53.7% of measures completed after treatment was concluded. CONCLUSIONS: Results highlight how the field's measurement of engagement has focused narrowly on attendance and on interventions that improve attendance. We consider promising new directions for capturing the multidimensional, dynamic, and subjective aspects of engagement, and for leveraging measurement in research and practice settings to feasibly and effectively identify, monitor, and address engagement challenges.

Performance of machine learning algorithms for glioma segmentation of brain MRI: a systematic literature review and meta-analysis.

OBJECTIVES: Different machine learning algorithms (MLAs) for automated segmentation of gliomas have been reported in the literature. Automated segmentation of different tumor characteristics can be of added value for the diagnostic work-up and treatment planning. The purpose of this study was to provide an overview and meta-analysis of different MLA methods. METHODS: A systematic literature review and meta-analysis was performed on the eligible studies describing the segmentation of gliomas. Meta-analysis of the performance was conducted on the reported dice similarity coefficient (DSC) score of both the aggregated results as two subgroups (i.e., high-grade and low-grade gliomas). This study was registered in PROSPERO prior to initiation (CRD42020191033). RESULTS: After the literature search (n = 734), 42 studies were included in the systematic literature review. Ten studies were eligible for inclusion in the meta-analysis. Overall, the MLAs from the included studies showed an overall DSC score of 0.84 (95% CI: 0.82-0.86). In addition, a DSC score of 0.83 (95% CI: 0.80-0.87) and 0.82 (95% CI: 0.78-0.87) was observed for the automated glioma segmentation of the high-grade and low-grade gliomas, respectively. However, heterogeneity was considerably high between included studies, and publication bias was observed. CONCLUSION: MLAs facilitating automated segmentation of gliomas show good accuracy, which is promising for future implementation in neuroradiology. However, before actual implementation, a few hurdles are yet to be overcome. It is crucial that quality guidelines are followed when reporting on MLAs, which includes validation on an external test set. KEY POINTS: • MLAs from the included studies showed an overall DSC score of 0.84 (95% CI: 0.82-0.86), indicating a good performance. • MLA performance was comparable when comparing the segmentation results of the high-grade gliomas and the low-grade gliomas. • For future studies using MLAs, it is crucial that quality guidelines are followed when reporting on MLAs, which includes validation on an external test set.

Characterization of standard work tools for intrathecal baclofen therapy.

PURPOSE: Intrathecal baclofen (ITB) has been an effective therapy since the 1980s, with widely reported revision, infection, and complication rates. Publications targeting surgical workflow have resulted in decreased infection and revision rates, but a standard workflow for the entire pathway has not been described. To present, define, and test standard work tools for patients receiving ITB to promote uniformity and standard of care in the field. METHODS: A multidisciplinary approach from the movement disorder program of a tertiary care center defined all steps comprising the ITB pathway, and then developed standard work tools to decrease variability with respect to preoperative workup, day of surgery protocol, post-operative care, and also evaluation and treatment with respect to pump infection or malfunction. RESULTS: Defined steps used at specific points of ITB pathway are presented with a single institution's outcome using the protocol from July 2017 to November 2020. A total of 60 procedures were performed. The overall complication rate was 14.5% at 6 months. Complications included an infection rate of 3.6% at 6 months, wound revision rate of 1.8% at 6 months, CSF leak rate of 1.7% at 6 months, and a 30-day readmission rate related to initial surgery of 6.7%. CONCLUSIONS: Workflow efficiency and optimization for ITB patients can be used to obtain lower complication rates compared to historical cohorts in literature. A single-center, retrospective review highlights this.

Probabilistic treatment planning for pancreatic cancer treatment: prospective incorporation of respiratory motion shows only limited dosimetric benefit.

BACKGROUND: We introduced a probabilistic treatment planning approach that prospectively incorporates respiratory-induced motion in the treatment plan optimization. The aim of this study was to determine the potential dosimetric benefit by comparing this approach to the use of an internal target volume (ITV). MATERIAL AND METHOD: We retrospectively compared the probabilistic respiratory motion-incorporated (RMI) approach to the ITV approach for 18 pancreatic cancer patients, for seven simulated respiratory amplitudes from 5 to 50 mm in the superior-inferior (SI) direction. For each plan, we assessed the target coverage (required: D98%≥95% of 50 Gy prescribed dose). For the RMI plans, we investigated whether target coverage was robust against daily variations in respiratory amplitude. We determined the distance between the clinical target volume and the 30 Gy isodose line (i.e. dose gradient steepness) in the SI direction. To investigate the clinical benefit of the RMI approach, we created for each patient an ITV and RMI treatment plan for the three-dimensional (3D) respiratory amplitudes observed on their pretreatment 4D computed tomography (4DCT). We determined Dmean, V30Gy, V40Gy and V50Gy for the duodenum. RESULTS: All treatment plans yielded good target coverage. The RMI plans were robust against respiratory amplitude variations up to 10 mm, as D98% remained ≥95%. We observed steeper dose gradients compared to the ITV approach, with a mean decrease from 25.9 to 19.2 mm for a motion amplitude of 50 mm. For the 4DCT motion amplitudes, the RMI approach resulted in a mean decrease of 0.43 Gy, 1.1 cm3, 1.4 cm3 and 0.9 cm3 for the Dmean, V30Gy, V40Gy and V50Gy of the duodenum, respectively. CONCLUSION: The probabilistic treatment planning approach yielded significantly steeper dose gradients and therefore significantly lower dose to surrounding healthy tissues than the ITV approach. However, the observed dosimetric gain for clinically observed respiratory motion amplitudes for this patient group was limited.

Motionless phase stepping in X-ray phase contrast imaging with a compact source.

X-ray phase contrast imaging offers a way to visualize the internal structures of an object without the need to deposit significant radiation, and thereby alleviate the main concern in X-ray diagnostic imaging procedures today. Grating-based differential phase contrast imaging techniques are compatible with compact X-ray sources, which is a key requirement for the majority of clinical X-ray modalities. However, these methods are substantially limited by the need for mechanical phase stepping. We describe an electromagnetic phase-stepping method that eliminates mechanical motion, thus removing the constraints in speed, accuracy, and flexibility. The method is broadly applicable to both projection and tomography imaging modes. The transition from mechanical to electromagnetic scanning should greatly facilitate the translation of X-ray phase contrast techniques into mainstream applications.

Permanent Pacemaker Implantation Early After Cardiac Surgery: A Descriptive Study of Pacemaker Utility After One Year of Follow-Up.

BACKGROUND: Complete heart block (CHB) is a common complication of cardiac surgery, which may resolve spontaneously. The optimal number of days to wait for resolution of CHB prior to proceeding with a permanent pacemaker (PPM) and the long-term utility of PPMs placed in this setting remain uncertain. METHODS AND RESULTS: This was a retrospective cohort study, which included members of Kaiser Permanente Northern California who had cardiac surgery, a PPM placed within 30 days after surgery, and one year of follow-up time. Chart review was performed to determine the frequency of ventricular pacing at each PPM interrogation visit up to one year after surgery. A PPM was categorized as underutilized at the time of an interrogation if none of the following were present: underlying rhythm <40 bpm, persistent CHB, or >1% ventricular pacing. The study included 247 patients with a mean time from cardiac surgery to PPM of 6.5 days. In 33 cases (13%), underutilized status was confirmed. The time from surgery to PPM implant was significantly higher in the underutilized group (8.1 ± 4.2 days vs. 6.2 ± 4.2 days, p = 0.003). CONCLUSIONS: The majority of PPMs placed early after cardiac surgery are not underutilized. In this retrospective, observational study, longer delay from surgery to PPM implantation was not associated with a greater likelihood that the PPM would be utilized long term. A prospective study is required to determine optimal timing of PPM implantation in this setting.

Differential Rates of Inadvertent Intravascular Injection during Lumbar Transforaminal Epidural Injections Using Blunt-Tip, Pencil-Point, and Catheter-Extension Needles.

OBJECTIVE: To quantify the incidence of inadvertent vascular penetration during lumbosacral transforaminal epidural injections using blunt-tip, pencil-point, and catheter-extension needles. STUDY DESIGN/SETTING: This is a prospective, observational, consecutive cohort study. SUBJECTS: Two hundred consecutive patients undergoing lumbosacral transforaminal epidural injections at an academic outpatient spine center. METHODS: Four hundred seventy-five fluoroscopically guided lumbosacral transforaminal epidural injections were performed on consecutively consenting patients by one interventional spine physician, using three different needle types. The presence or absence of vascular uptake was determined during contrast injection under live fluoroscopy. RESULTS: Vascular uptake of contrast was observed in 58 of the total 475 injections, for an overall incidence of 12.2%. By needle type, the incidence of inadvertent vascular uptake was 16.6% (26/157) in the pencil-point group, 15.6% (24/154) in the blunt-tip group, and 4.9% (8/164) in the catheter-extension group. The difference in rates is statistically significant between the catheter-extension needle group and both the pencil-point group (P = 0.0009) and blunt-tip group (P = 0.0024). A secondary analysis was performed to quantify the incidence of functional pitfalls between needle groups, with a significantly lower incidence in the pencil-point group compared to both the catheter-extension (P = 0.0148) and blunt-tip needle (P = 0.0288) groups. CONCLUSIONS: Blunt-tip and pencil-point needles have comparable risk of inadvertent vascular injection during lumbosacral transforaminal injections. Catheter-extension needles demonstrated a reduce incidence of vascular uptake, but also result in a significantly higher rate of functional pitfalls that limits their usefulness in routine practice.

Bionanosensor utilizing single-layer graphene for the detection of iridovirus.

CONTEXT: Iridoviruses, a group of double-stranded DNA viruses, pose a significant threat to various aquatic animals, causing substantial economic losses in aquaculture and impacting ecosystem health. Early and accurate detection of these viruses is crucial for effective disease management and control. Conventional diagnostic methods, including polymerase chain reaction (PCR) and virus isolation, often require specialized laboratories, skilled personnel, and considerable time. This highlights the need for rapid, sensitive, and cost-effective diagnostic tools for iridovirus detection. Single-layer graphene, a two-dimensional material with unique properties like high surface area, excellent electrical conductivity, and chemical stability, has emerged as a versatile platform for biosensing applications. This paper explores the potential of employing single-layer graphene in the development of a bionanosensor for the sensitive and rapid detection of iridoviruses. The aim of the present investigation is to develop a sensor by analyzing the vibrational responses of single-layer graphene sheets (SLGS) with attached microorganisms. Graphene-based virus sensors typically rely on the interaction between the virus and the graphene surface, which lead to changes in the frequency response of graphene. This change is measured and used to detect the presence of the virus. Its high surface-to-volume ratio and sensitivity to changes in its frequency make it a highly sensitive platform for virus detection. METHODS: We employ finite element method (FEM) analysis to model the sensor's performance and optimize its design parameters. The simulation results highlight the sensor's potential for achieving high sensitivity and rapid detection of iridovirus. Bridged and simply supported with roller support boundary conditions applied at the ends of SLG structure. Simulations have been performed to see how SLG behaves when used as sensors. A single-layer graphene armchair SLG (5,5) with 50-nm length exhibits its highest frequency vibration at 8.66 × 106 Hz, with a mass of 1.2786 Zg. In contrast, a zigzag-SLG with a (18,0) configuration has its lowest frequency vibration at 2.82 × 105 Hz. This aids in comprehending the thresholds of detection and the influence of factors such as size, and boundary conditions on sensor effectiveness. These biosensors can be especially helpful in biological sciences and the medical field since they can considerably improve the treatment of patients, cancer early diagnosis, and pathogen identification when used in clinical environments.

Feasibility, safety and effectiveness of the enhanced recovery after surgery protocol in patients undergoing liver resection.

Backgrounds/Aims: The implementation of enhanced recovery after surgery (ERAS) protocols has demonstrated significant advantages for patients by mitigating surgical stress and expediting recovery across a spectrum of surgical procedures worldwide. This investigation seeks to assess the effectiveness of the ERAS protocol specifically in the context of major liver resections within our geographical region. Methods: Our department conducted retrospective analysis of prospectively collected data, gathered from consenting individuals who underwent liver resections from January 2018 to December 2023. The assessment encompassed baseline characteristics, preoperative indications, surgical outcomes, and postoperative complications among patients undergoing liver surgery. Results: Among the included 184 patients (73 standard care, 111 ERAS program), the baseline characteristics were similar. Median postoperative hospital stay differed significantly: 5 days (range: 3-13 days) in ERAS, and 11 days (range: 6-22 days) in standard care (p < 0.001). Prophylactic abdominal drainage was less in ERAS (54.9%) than in standard care (86.3%, p < 0.001). Notably, in ERAS, 88.2% initiated enteral feeding orally on postoperative day 1, significantly higher than in standard care (47.9%, p < 0.001). Early postoperative mobilization was more common in ERAS (84.6%) than in standard care (36.9%, p < 0.001). Overall complication rates were 21.9% in standard care, and 8.1% in ERAS (p = 0.004). Conclusions: Our investigation highlights the merits of ERAS protocol; adherence to its diverse components results in significant reduction in hospital length of stay, and reduced occurrence of postoperative complications, improving short-term recovery post liver resection.

Real-World Evidence to Reinforce Clinical Trial Evidence in Health Technology Assessment: A Critical Review of Real-World Evidence Requirements from Seven Countries and Recommendations to Improve Acceptance.

BACKGROUND: Real-world evidence (RWE) can reinforce clinical trial evidence in health technology assessment (HTA). OBJECTIVES: Review HTA bodies' (HTAbs) requirements for RWE, real uses, and acceptance across seven countries (Brazil, Canada, France, Germany, Italy, Spain, and the United Kingdom) and outline recommendations that may improve acceptance of RWE in efficacy/effectiveness assessments and appraisals processes. METHODS: RWE requirements were summarized based on HTAbs' guidelines. Acceptance by HTAbs was evaluated based on industry experience and case studies. RESULTS: As of June 2022, RWE methodological guidelines were in place in three of the seven countries. HTAbs typically requested analyses based on local data sources, but the preferred study design and data sources differed. HTAbs had individual submission, assessment, and appraisal processes; some allowed early meetings for the protocol and/or results validation, though few involved external experts or medical societies to provide input to assessment and appraisal. The extent of submission, assessment, and appraisal requirements did not necessarily reflect the degree of acceptance. CONCLUSION: All the countries reviewed face common challenges regarding the use of RWE. Our proposals address the need to facilitate collaboration and communication with industry and regulatory agencies and the need for specific guidelines describing RWE design and criteria of acceptance throughout the assessment and appraisal processes.

Genes and gene networks underlying spatial cognition in food-caching chickadees.

Substantial progress has been made in understanding the genetic architecture of phenotypes involved in a variety of evolutionary processes. Behavioral genetics remains, however, among the least understood. We explore the genetic architecture of spatial cognitive abilities in a wild passerine bird, the mountain chickadee (Poecile gambeli). Mountain chickadees cache thousands of seeds in the fall and require specialized spatial memory to recover these caches throughout the winter. We previously showed that variation in spatial cognition has a direct effect on fitness and has a genetic basis. It remains unknown which specific genes and developmental pathways are particularly important for shaping spatial cognition. To further dissect the genetic basis of spatial cognitive abilities, we combine experimental quantification of spatial cognition in wild chickadees with whole-genome sequencing of 162 individuals, a new chromosome-scale reference genome, and species-specific gene annotation. We have identified a set of genes and developmental pathways that play a key role in creating variation in spatial cognition and found that the mechanism shaping cognitive variation is consistent with selection against mildly deleterious non-coding mutations. Although some candidate genes were organized into connected gene networks, about half do not have shared regulation, highlighting that multiple independent developmental or physiological mechanisms contribute to variation in spatial cognitive abilities. A large proportion of the candidate genes we found are associated with synaptic plasticity, an intriguing result that leads to the hypothesis that certain genetic variants create antagonism between behavioral plasticity and long-term memory, each providing distinct benefits depending on ecological context.

Impact of point vacancy defects on vibrational behaviour of three-walled carbon nanotubes.

CONTEXT: Through experimental observations and reports, various challenges have been identified in carbon nanotubes (CNT), including Stone Wales (SW) flaws and position flaws. Among these imperfections, point vacancies are the most prevalent in the CNT lattice. However, there is currently no established method for detecting these issues, and the influence of these flaws on the vibrational properties of three-walled carbon nanotubes (TWCNTs) remains uncertain. This research paper introduces a novel approach that utilizes vibrational analysis to detect flaws in TWCNTs. By conducting the first investigation into the impact of point vacancies on the vibrational modal frequencies of TWCNTs, our study bridges these knowledge gaps. METHODS: This study examines the impact of defect quantity on various types of TWCNTs and investigates the vibrational properties of TWCNTs with point vacancies using a molecular structural mechanics technique. A total of 432 TWCNT models were simulated using molecular structural mechanics (MSM), and their modes were identified through finite element (FE) analysis. The fundamental vibration's natural frequency in TWCNTs with defects was then determined. The findings indicate that the depth of the mode shape is influenced by the TWCNTs' diameter, the extent of point vacancy defects, and the boundary condition. It was observed that as the number of vacancy defects increases from 0 to 4%, the natural frequency decreases. The study also establishes the order of TWCNTs with the highest natural vibrational frequency at 0%-point vacancy and [Formula: see text] a given attached mass, which follows the sequence of chiral, armchair, and zigzag TWCNTs.

Nanoresonator vibrational behaviour analysis of single- and double-layer graphene with atomic vacancy and pinhole defects.

CONTEXT: Nanosensors and actuators are frequently made of graphene. Any defect in the graphene's manufacturing has an impact on its sensing performance and on its dynamic behaviour. Using a molecular dynamics technique, the influence of pinhole defects and atomic defects on the performance parameters of single-layer graphene sheets (SLGSs) and double-layer graphene sheets (DLGSs) with various boundary conditions and lengths is explored. In contrast to the perfect nanostructure of a graphene sheet, defects are described as holes formed by atomic vacancies. As the number of defects increases, the simulation results show that the presence of defects has the greatest impact on the resonance frequency of SLGSs and DLGSs. The influence of pinhole defect (PD) and atomic vacancy defect (AVD) on armchair, zigzag, and chiral SLGSs and DLGSs was investigated in this article using molecular dynamics simulation. The influence of both types of defects is largest when it is adjacent to the fixed support for all three different types of graphene sheets, i.e. armchair, zigzag, and chiral. METHODS: The structure of the graphene sheet has been created using ANSYS APDL software. In the structure of the graphene sheet, atomic and pinhole defects have been generated. SLG and DLG sheets are modelled using a space frame structure that is identical to a three-dimensional beam. Dynamic analysis of single-layer and double-layer graphene sheets performed with different lengths using the atomistic finite element method. The interlayer separation in the form of Van der Waals interaction is modelled using characteristic spring element (Combin14). The upper and lower sheets of DLGSs are described as elastic beams connected by a spring element. With atomic vacancy defect for the bridged boundary condition, the highest frequency of 2.86 × 108 Hz was found for zigzag DLG (20 0) and with same boundary condition for pinhole defect 2.79 × 108 Hz frequency achieved. In a single-layer graphene sheet with an atomic vacancy and cantilever boundary condition, the maximum efficiency was 4.13 × 103 Hz for SLG (20 0), while in a pinhole defect, it produced 2.73 × 107 Hz. Moreover, the elastic parameters of beam components are calculated using the mechanical properties of covalent bonds between carbon atoms in the hexagonal lattice. The model has been tested against previous research. The focus of this research is to develop a mechanism for determining how defects affect graphene frequency band in application as nano resonators.

Identification of microbes using single-layer graphene-based nano biosensors.

CONTEXT: Graphene based nano sensors have huge potential in an era of sensor technology. The objective of this study is to create a sensor by investigating the vibration responses of cantilever and bridged boundary conditioned single layer graphene sheets (SLGS) with various attached microorganisms on the tip and at the centre of the sheet. The Parvoviridae, Flaviviridae, and Polyomaviridae biological substances have been comprehensively investigated here. For the Parvoviridae, Polyomaviridae, and Flaviviridae categories of targeted microbes, the sizes are 21nm, 40nm, and 45nm, respectively. The Parvoviridae family has a maximum frequency of 1.87x107 Hz with a cantilever condition and a mass of 4.2441 Zg, and for a bridged condition, it demonstrates a maximum frequency of 1.23x108 Hz with the same mass on armchair SLG (5 5). The data analysis shows that 3.0041 Zg mass of the Mimivirus has the lowest frequency. It demonstrates explicitly that the rate of frequency decreases as the value of mass increases. When compared to chiral SLG, the armchair single layer graphene sheet performs better. The research indicates that the dynamic properties are significantly influenced by the mass of various biological organisms. The application of this sensor will enable the detection of microorganisms or viruses that can be connected to SLG. METHODS: In this research, the application of Single Layer Graphene (SLG) as a virus sensing device is explored. Atomistic finite element method (AFEM) has been used to carry out the dynamic analysis of SLG. Molecular dynamic analysis and simulations have been performed to see how SLG behaves when employed as sensors for biological entities and when they are exposed to bridged and cantilever boundary conditions. The frequency analysis was performed using ANSYS APDL software. SLG of various chirality has been utilised in the investigation. By altering the applied mass of a biological object, the difference in frequency observed. The idea behind mass detection employing nano biosensors is built on the concept that the stiffness of a biomolecule changes as its mass changes, making the resonant frequency extremely sensitive to that change. A shift in the resonance frequency results from a change in the associated mass on the graphene sheet. The main challenge in mass detection is estimating the variation in resonant frequency driven by the mass of the connected molecule. The SLG-based biosensor has a specific application in the early identification of diseases. The biosensor investigated in this article is novel, whereas the biosensors that are presently on the market operate using the ionization method. The simulations result shows SLG based biosensor's sensitivity considerably faster than an existing one.

Characterization, Anti-proliferative Activity, and Bench-Scale Production of Novel pH-Stable and Thermotolerant L-Asparaginase from Bacillus licheniformis PPD37.

Bacterial L-asparaginase (LA) is a chemotherapeutic drug that has remained mainstay of cancer treatment for several decades. LA has been extensively used worldwide for the treatment of acute lymphoblastic leukemia (ALL). A halotolerant bacterial strain Bacillus licheniformis sp. isolated from marine environment was used for LA production. The enzyme produced was subjected to purification and physico-chemical characterisation. Purified LA was thermotolerant and demonstrated more than 90% enzyme activity after 1 h of incubation at 80 °C. LA has also proved to be resistant against pH gradient and retained activity at pH ranging from 3.0 to 10. The enzyme also had high salinity tolerance with 90% LA activity at 10% NaCl concentration. Detergents like Triton X-100 and Tween-80 were observed to inhibit LA activity while more than 70% catalytic activity was maintained in the presence of metals. Electrophoretic analysis revealed that LA is a heterodimer (~ 63 and ~ 65 kDa) and has molecular mass of around 130 kDa in native form. The kinetic parameters of LA were tested with LA having low Km value of 1.518 µM and Vmax value of 6.94 µM/min/mL. Purified LA has also exhibited noteworthy antiproliferative activity against cancer cell lines-HeLa, SiHa, A549, and SH-SY-5Y. In addition, bench-scale LA production was conducted in a 5-L bioreactor using moringa leaves as cost-effective substrate.

A Novel Inhibitor of DKK1/LRP6 Interactions Against the Alzheimer Disease: An Insilco Approach.

The activation of the Wnt signaling pathway is implicated in a neuroprotective mechanism against the Alzheimer disease. When this pathway is blocked, it activates GSK3 beta, leading to tau hyperphosphorylation and the apoptosis of neurons. Dickkopf-related protein 1 (DKK1) is a protein that competes with the Wnt ligand for the low-density lipoprotein receptor-related protein 6 (LRP6) receptor's binding, interrupting the Wnt-induced Fzd-Wnt-LRP6 complex. This counteracts Wnt's neuroprotective effect and contributes to the progression of the Alzheimer disease. The aim of this study was to use in silico approach to develop new agents that can combat the Alzheimer disease by targeting the interaction between DKK1 and LRP6. To achieve this, we conducted a virtual screening (Vsw) of the Asinex-CNS database library (n = 54 513) compounds against a generated grid in LRP6 protein. From this screening, we selected 6 compounds based on their docking score and performed molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations on the selected ligands. Next, we evaluated the Absorption, Distribution, Metabolism, and Excretion (ADME) results of the 6 screened compounds using the Quick prop module of Schrödinger. We then employed several computational techniques, including PCA (Principal Component Analysis), DCCM (Dynamic Cross-Correlation Map), molecular dynamics simulation, and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA)-based negative binding free energy (BFE) calculation, to further analyze the compounds. Our extensive computational analysis resulted in the identification of 3 potential hits, LAS 29757582, LAS 29984441, and LAS 29757942. These compounds were found to block the interaction of DKK1 with LRP6 (A and B interface) protein, and their potential as therapeutic agents was supported by negative BFE calculation. Therefore, these compounds show potential as possible therapeutic agents for treating the Alzheimer disease through targeting the interaction between DKK1 and LRP6.

Assessing the Impact of Uterine Artery Doppler and Low-Dose Aspirin on Fetomaternal Outcome: A Prospective Study in Low-Risk Pregnant Women in Western Part of India.

Introduction Fetal growth restriction (FGR) and pregnancy-induced hypertension (PIH) are significant and clinically relevant complications observed in many pregnancies. Early prediction of these complications may be possible through the assessment of the umbilical artery pulsatility index (UAPI). However, its utility in routine practice for otherwise normal pregnancy needs further exploration in India. Objectives This study aimed to evaluate the potential benefits of incorporating UAPI for the timely use of low-dose aspirin in preventing FGR and PIH in a tertiary care hospital in the western part of India. Methodology A prospective study was conducted involving 64 low-risk (i.e., not having any feature of high-risk pregnancy) pregnant women selected from routine antenatal care outpatient departments over a period of two years. All women underwent uterine artery Doppler examination during the 11-13+6 weeks of pregnancy and those who had high UAPI received low-dose (150 mg) aspirin till the 35th week. The incidence of FGR and PIH was analyzed and compared between high UAPI and normal UAPI pregnancy. Results A total of 64 pregnant women with a mean age of 27.11±4 years participated in the study. Among the women, eight (12.5%) were found to have high UAPI and were put on aspirin. Among those eight women, two developed PIH. In the normal UAPI group, nine (16.07%) developed PIH (p-value = 0.62). FGR was found in one case among the eight who received aspirin and in eight cases among the 56 who had normal UAPI (p-value > 0.99). Conclusion The study concluded that despite having normal UAPI, women categorized as low-risk may develop PIH and FGR. Hence, the routine use of UAPI should be investigated in further cohort studies using a large sample to draw a generalizable conclusion for the Indian population.