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1.
Langmuir ; 40(10): 5040-5059, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38419155

ABSTRACT

Polluted water has become a concern for the scientific community as it causes many severe threats to living beings. Detection or removal of contaminants present in wastewater and attaining purity of water that can be used for various purposes are a primary responsibility. Different treatment methods have already been used for the purification of sewage. There is a need for low-cost, highly selective, and reusable materials that can efficiently remove pollutants or purify contaminated water. In this regard, MOFs have shown significant potential for applications such as supercapacitors, drug delivery, gas storage, pollutant adsorption, etc. The outstanding structural diversity, substantial surface areas, and adjustable pore sizes of MOFs make them superior candidates for wastewater treatment. This Review provides an overview of the interaction science and engineering (kinetic and thermodynamic aspects with interactions) underpinning MOFs for water purification. First, fundamental strategies for the synthesis methods of MOFs, different categories, and their applicability in wastewater treatment are summarized, followed by a detailed explanation of various interaction mechanisms. Finally, current challenges and future outlooks for research on MOF materials toward the adsorption of hazardous components are discussed. A new avenue for modifying their structural characteristics for the adsorption and separation of hazardous materials, which will undoubtedly direct future work, is also summarized.

2.
BMC Health Serv Res ; 24(1): 180, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38331762

ABSTRACT

BACKGROUND: Improving screening and triage practices is essential for early severity assessments at the first point of contact and ensuring timely attention by healthcare workers (HCWs). The main objective of this study was to explore the triage process among febrile patients and HCWs in the emergency department (ED) of a tertiary care hospital in a resource-constrained setting. METHODS: This qualitative study was conducted from March to May 2023 at the ED of Tribhuvan University Teaching Hospital (TUTH), Nepal. The study included in-depth interviews with febrile patients (n = 15) and HCWs (n = 15). Additionally, direct observation notes (n = 20) were collected to document the triage process and patients' experiences in the ED. Data underwent thematic analysis using the Interpretative Phenomenological Analysis (IPA) approach. RESULTS: The ED of TUTH offered comprehensive triage services with clear delineation for the severity of febrile patients in line with the World Health Organization (WHO) guidelines. Nonetheless, challenges and constraints were identified. In the ED, evenings were generally the busiest period, and the triage process was not thorough during night shifts. Perception of triage was limited among patients and variable among HCWs. Digitalizing recordings of patient information including payment was deemed necessary for effective management of patients' waiting times at the triage station. High patient throughput added pressure on HCWs and had a potential influence on the delivery of services. Availability of medical equipment and space were also identified as challenges, with patients sometimes compelled to share beds. There were constraints related to waste disposal, hygiene, cleanliness, and the availability and maintenance of washrooms. Febrile patients experienced delays in receiving timely consultations and laboratory investigation reports, which affected their rapid diagnosis and discharge; nonetheless, patients were satisfied with the overall healthcare services received in the ED. CONCLUSIONS: Improving current triage management requires resource organization, including optimizing the waiting time of patients through a digitalized system. Urgent priorities involve upgrading visitor facilities, patient consultations, laboratory investigations, hygiene, and sanitation. HCWs' recommendations to resource the ED with more equipment, space, and beds and a dedicated triage officer to ensure 24-hour service, together with training and incentives, warrant further attention.


Subject(s)
Emergency Medical Services , Triage , Humans , Tertiary Care Centers , Nepal , Delivery of Health Care , Emergency Service, Hospital , Health Personnel , Hospitals, University
3.
Surv Ophthalmol ; 69(2): 179-189, 2024.
Article in English | MEDLINE | ID: mdl-37778668

ABSTRACT

Diseases leading to retinal cell loss can cause severe visual impairment and blindness. The lack of effective therapies to address retinal cell loss and the absence of intrinsic regeneration in the human retina leads to an irreversible pathological condition. Progress in recent years in the generation of human three-dimensional retinal organoids from pluripotent stem cells makes it possible to recreate the cytoarchitecture and associated cell-cell interactions of the human retina in remarkable detail. These human three-dimensional retinal organoid systems made of distinct retinal cell types and possessing contextual physiological responses allow the study of human retina development and retinal disease pathology in a way animal model and two-dimensional cell cultures were unable to achieve. We describe the derivation of retinal organoids from human pluripotent stem cells and their application for modeling retinal disease pathologies, while outlining the opportunities and challenges for its application in academia and industry.


Subject(s)
Pluripotent Stem Cells , Retinal Diseases , Animals , Humans , Retina , Pluripotent Stem Cells/metabolism , Organoids/metabolism , Retinal Diseases/drug therapy , Retinal Diseases/metabolism , Drug Discovery , Cell Differentiation
4.
Sci Rep ; 13(1): 16175, 2023 09 27.
Article in English | MEDLINE | ID: mdl-37759071

ABSTRACT

Deregulation of vascular endothelial growth factor (VEGF) levels leads to retinopathy of prematurity (ROP). Vitamin D (VIT-D) is known to regulate VEGF in an oxygen dependent manner. The purpose of this study was to correlate tear levels of VEGF and VIT-D with different ROP stages in preterm infants. In this prospective cross-sectional study, we enrolled 104 pre-term infants. They were grouped into: Group-1 (Classical ROP) and Group-2 (Aggressive ROP), which were further subdivided into Group-1A (progressing), Group-1B (regressing), Group-2A (pre-treatment), and Group-2B (post-treatment). Tear VEGF and VIT-D levels and their association with different ROP stages were assessed. Stage 1 and stage 2 had higher whereas stage 3 had lower VEGF levels in Group-1B compared to Group-1A. Stage 1 and stage 3 showed higher levels of VIT-D with no difference in stage 2 in Group-1B compared to Group-1A., Group-2B showed higher VEGF and lower VIT-D levels compared to Group-2A. Presence of a positive correlation at an early stage (stage 1) of ROP and a negative correlation at a more advanced stage (stage 3) of ROP with VIT-D and VEGF implies stage-specific distinct signaling crosstalk. These findings suggest that VIT-D supplementation may have the potential to modify the course and outcome of ROP.


Subject(s)
Infant, Premature , Retinopathy of Prematurity , Infant , Humans , Infant, Newborn , Vascular Endothelial Growth Factor A , Vitamin D , Prospective Studies , Retinopathy of Prematurity/metabolism , Cross-Sectional Studies , Gestational Age
5.
Chemphyschem ; 24(18): e202300032, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37437164

ABSTRACT

High-voltage alkali metal-ion batteries (AMIBs) require a non-hazardous, low-cost, and highly stable electrolyte with a large operating potential and rapid ion conductivity. Here, we have reported a halogen-free high-voltage electrolyte based on SiB11 (BO)12 - . Because of the weak π-orbital interaction of -BO as well as the mixed covalent and ionic interaction between SiB11 -cage and -BO ligand, SiB11 (BO)12 - has colossal stability. SiB11 (BO)12 - possesses extremely high vertical detachment energy (9.95 eV), anodic voltage limit (∼10.05 V), and electrochemical stability window (∼9.95 V). Furthermore, SiB11 (BO)12 - is thermodynamically stable at high temperatures, and its large size allows for faster cation movement. The alkali salts MSiB11 (BO)12 (M=Li, Na, and K) are easily dissociated into ionic components. Electrolytes based on SiB11 (BO)12 - greatly outperform commercial electrolytes. In short, SiB11 (BO)12 - -based compound is demonstrated to be a high-voltage electrolyte for AMIBs.

6.
PLoS One ; 18(7): e0288044, 2023.
Article in English | MEDLINE | ID: mdl-37406006

ABSTRACT

The retrieval of important information from a dataset requires applying a special data mining technique known as data clustering (DC). DC classifies similar objects into a groups of similar characteristics. Clustering involves grouping the data around k-cluster centres that typically are selected randomly. Recently, the issues behind DC have called for a search for an alternative solution. Recently, a nature-based optimization algorithm named Black Hole Algorithm (BHA) was developed to address the several well-known optimization problems. The BHA is a metaheuristic (population-based) that mimics the event around the natural phenomena of black holes, whereby an individual star represents the potential solutions revolving around the solution space. The original BHA algorithm showed better performance compared to other algorithms when applied to a benchmark dataset, despite its poor exploration capability. Hence, this paper presents a multi-population version of BHA as a generalization of the BHA called MBHA wherein the performance of the algorithm is not dependent on the best-found solution but a set of generated best solutions. The method formulated was subjected to testing using a set of nine widespread and popular benchmark test functions. The ensuing experimental outcomes indicated the highly precise results generated by the method compared to BHA and comparable algorithms in the study, as well as excellent robustness. Furthermore, the proposed MBHA achieved a high rate of convergence on six real datasets (collected from the UCL machine learning lab), making it suitable for DC problems. Lastly, the evaluations conclusively indicated the appropriateness of the proposed algorithm to resolve DC issues.


Subject(s)
Algorithms , Machine Learning , Cluster Analysis , Data Mining/methods , Benchmarking
8.
Graefes Arch Clin Exp Ophthalmol ; 261(11): 3051-3065, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37074409

ABSTRACT

BACKGROUND: Keratoconus is a corneal ectatic disease caused by stromal thinning leading to astigmatism and progressive loss of vision. Loss of the keratocytes and excessive degradation of collagen fibres by matrix metalloproteinases are the molecular signatures of the disease. Despite several limitations, corneal collagen cross-linking and keratoplasty are the most widely used treatment options for keratoconus. In the pursuit of alternative treatment modalities, clinician scientists have explored cell therapy paradigms for treating the condition. METHODS: Articles pertaining to keratoconus cell therapy with relevant key words were used to search in PubMed, Researchgate, and Google Scholar. The articles were selected based on their relevance, reliability, publication year, published journal, and accessibility. RESULTS: Various cellular abnormalities have been reported in keratoconus. Diverse cell types such as mesenchymal stromal cells, dental pulp cells, bone marrow stem cells, haematopoietic stem cells, adipose-derived stem cells apart from embryonic and induced pluripotent stem cells can be used for keratoconus cell therapy. The results obtained show that there is a potential for these cells from various sources as a viable treatment option. CONCLUSION: There is a need for consensus with respect to the source of cells, mode of delivery, stage of disease, and duration of follow-up, to establish a standard operating protocol. This would eventually widen the cell therapy options for corneal ectatic diseases beyond keratoconus.

9.
Indian J Ophthalmol ; 71(4): 1270-1275, 2023 04.
Article in English | MEDLINE | ID: mdl-37026258

ABSTRACT

Dry eye disease (DED) is a multifactorial and common ophthalmic disease that has a tremendous effect on the quality of life. It is now becoming a public health concern because of our changing lifestyle and environment. The current treatment modalities, artificial tear substitutes, and anti-inflammatory therapy are directed at dry eye symptoms. One of the major drivers for DED is oxidative stress, and the polyphenol group of natural compounds has the potential to reduce the same. Resveratrol, widely found in the skin of grapes and nuts, has antioxidative and anti-inflammatory properties. It has been shown to have beneficial effects in glaucoma, age-related macular degeneration, retinopathy of prematurity, uveitis, and diabetic retinopathy. Studies have also explored the beneficial effects of resveratrol in DED, making it as a promising therapeutic molecule. Resveratrol has not yet reached clinical application because of difficulty in deliverability and low bioavailability. In this review, we explore the potential of resveratrol in DED treatment based on various in vitro and in vivo studies.


Subject(s)
Dry Eye Syndromes , Quality of Life , Infant, Newborn , Humans , Resveratrol/therapeutic use , Dry Eye Syndromes/diagnosis , Tears , Anti-Inflammatory Agents/therapeutic use
11.
Acta Biomater ; 163: 63-77, 2023 06.
Article in English | MEDLINE | ID: mdl-35259515

ABSTRACT

The viscoelastic mechanical behavior of collagenous tissues has been studied extensively at the macroscale, yet a thorough quantitative understanding of the time-dependent mechanics of the basic building blocks of tissues, the collagen fibrils, is still missing. In order to address this knowledge gap, stress relaxation and creep tests at various stress (5-35 MPa) and strain (5-20%) levels were performed with individual collagen fibrils (average diameter of fully hydrated fibrils: 253 ± 21 nm) in phosphate buffered saline (PBS). The experimental results showed that the time-dependent mechanical behavior of fully hydrated individual collagen fibrils reconstituted from Type I calf skin collagen, is described by strain-dependent stress relaxation and stress-dependent creep functions in both the heel-toe and the linear regimes of deformation in monotonic stress-strain curves. The adaptive quasilinear viscoelastic (QLV) model, originally developed to capture the nonlinear viscoelastic response of collagenous tissues, provided a very good description of the nonlinear stress relaxation and creep behavior of the collagen fibrils. On the other hand, the nonlinear superposition (NSP) model fitted well the creep but not the stress relaxation data. The time constants and rates extracted from the adaptive QLV and the NSP models, respectively, pointed to a faster rate for stress relaxation than creep. This nonlinear viscoelastic behavior of individual collagen fibrils agrees with prior studies of macroscale collagenous tissues, thus demonstrating consistent time-dependent behavior across length scales and tissue hierarchies. STATEMENT OF SIGNIFICANCE: Pure stress relaxation and creep experiments were conducted for the first time with fully hydrated individual collagen fibrils. It is shown that collagen nanofibrils have a nonlinear time-dependent behavior which agrees with prior studies on macroscale collagenous tissues, thus demonstrating consistent time-dependent behavior across length scales and tissue hierarchies. This new insight into the non-linear viscoelastic behavior of the building blocks of mammalian collagenous tissues may serve as the foundation for improved macroscale tissue models that capture the mechanical behavior across length scales.


Subject(s)
Collagen , Mammals , Animals , Stress, Mechanical , Viscosity , Collagen/physiology , Extracellular Matrix , Collagen Type I , Elasticity , Models, Biological
12.
Indian J Crit Care Med ; 26(9): 987-992, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36213700

ABSTRACT

Objective: To study the use of serial ultrasound gastric residual volume (GRV) measurements in predicting feed intolerance in critically ill patients. Patients and methods: This study was conducted in various intensive care units (ICUs) of All India Institute of Medical Sciences, New Delhi. Forty-three critically ill patients aged more than 18 years were studied for a total of 130 enteral feeding days. Gastric residual volume was obtained by calculating the antral cross-sectional area (CSA), which is the product of anteroposterior (AP) and craniocaudal (CC) diameters of gastric antrum obtained using ultrasound in the right lateral decubitus position. A baseline measurement was done before the initiation of the enteral feed and termed GRV0, the ultrasound scanning was repeated every 1 hour for the first 4 hours and termed GRV1, GRV2, GRV3, and GRV4, respectively, and the patients were watched for feed intolerance. The receiver operating characteristic (ROC) curves were constructed to correlate the GRV at each time with feed intolerance. Results: The data from 43 medical and surgical critically ill patients were analyzed. Out of 130 feeding days, 13 were noted to be feed intolerant. Gastric residual volume at the end of the fourth hour of feed, that is, GRV4 was the best predictor of feed intolerance with 99.3% area under the curve (AUROC), sensitivity of 99%, specificity of 99.3%, and 95% CI, 0.89-0.98 followed by GRV3, with AUROC of 96% and sensitivity and specificity of 92.3 and 96%, respectively, with 95% CI, 0.92-0.99. How to cite this article: Ankalagi B, Singh PM, Rewari V, Ramachandran R, Aggarwal R, Soni KD, et al. Serial Ultrasonographic-measurement of Gastric Residual Volume in Critically Ill Patients for Prediction of Gastric Tube Feed Intolerance. Indian J Crit Care Med 2022;26(9):987-992.

13.
ACS Omega ; 7(31): 27116-27125, 2022 Aug 09.
Article in English | MEDLINE | ID: mdl-35967049

ABSTRACT

Corrosion of metal/steel is a major concern in terms of safety, durability, cost, and environment. We have studied a cost-effective, nontoxic, and environmentally friendly pyromellitic diimide (PMDI) compound as a corrosion inhibitor for galvanized steel through density functional theory. An atomic-scale engineering through the functionalization of PMDI is performed to showcase the enhancement in corrosion inhibition and strengthen the interaction between functionalized PMDI (F-PMDI) and zinc oxide (naturally existing on galvanized steel). PMDI is functionalized with methyl/diamine groups (inh1 (R = -CH3, R' = -CH3), inh2 (R = -CH3, R' = -CH2CH2NH2), and inh3 (R = -C6H3(NH2)2, R' = -CH2CH2NH2). The corrosion inhibition parameters (e.g., orbital energies, electronegativity, dipole moment, global hardness, and electron transfer) indicate the superior corrosion inhibition performance of inh3 (inh3 > inh2 > inh1). Inh3 (∼182.38 kJ/mol) strongly interacts with ZnO(101̅0) compared to inh2 (∼122.56 kJ/mol) and inh1 (∼119.66 kJ/mol). The superior performance of inh3 has been probed through charge density and density of states. Larger available states of N and H (of inh3) interact strongly with Zn and Osurf (of the surface), respectively, creating N-Zn and H-Osurf bonds. Interestingly, these bonds only appear in inh3. The charge accumulation on Osurf, and depletion on H(s), further strengthens the bonding between inh3 and ZnO(101̅0). The microscopic understanding obtained in this study will be useful to develop low-cost and efficient corrosion inhibitors for galvanized steel.

14.
Malar J ; 21(1): 122, 2022 Apr 12.
Article in English | MEDLINE | ID: mdl-35413904

ABSTRACT

BACKGROUND: Microscopic examination of Giemsa-stained blood films remains the reference standard for malaria parasite detection and quantification, but is undermined by difficulties in ensuring high-quality manual reading and inter-reader reliability. Automated parasite detection and quantification may address this issue. METHODS: A multi-centre, observational study was conducted during 2018 and 2019 at 11 sites to assess the performance of the EasyScan Go, a microscopy device employing machine-learning-based image analysis. Sensitivity, specificity, accuracy of species detection and parasite density estimation were assessed with expert microscopy as the reference. Intra- and inter-device reliability of the device was also evaluated by comparing results from repeat reads on the same and two different devices. This study has been reported in accordance with the Standards for Reporting Diagnostic accuracy studies (STARD) checklist. RESULTS: In total, 2250 Giemsa-stained blood films were prepared and read independently by expert microscopists and the EasyScan Go device. The diagnostic sensitivity of EasyScan Go was 91.1% (95% CI 88.9-92.7), and specificity 75.6% (95% CI 73.1-78.0). With good quality slides sensitivity was similar (89.1%, 95%CI 86.2-91.5), but specificity increased to 85.1% (95%CI 82.6-87.4). Sensitivity increased with parasitaemia rising from 57% at < 200 parasite/µL, to ≥ 90% at > 200-200,000 parasite/µL. Species were identified accurately in 93% of Plasmodium falciparum samples (kappa = 0.76, 95% CI 0.69-0.83), and in 92% of Plasmodium vivax samples (kappa = 0.73, 95% CI 0.66-0.80). Parasite density estimates by the EasyScan Go were within ± 25% of the microscopic reference counts in 23% of slides. CONCLUSIONS: The performance of the EasyScan Go in parasite detection and species identification accuracy fulfil WHO-TDR Research Malaria Microscopy competence level 2 criteria. In terms of parasite quantification and false positive rate, it meets the level 4 WHO-TDR Research Malaria Microscopy criteria. All performance parameters were significantly affected by slide quality. Further software improvement is required to improve sensitivity at low parasitaemia and parasite density estimations. Trial registration ClinicalTrials.gov number NCT03512678.


Subject(s)
Malaria, Falciparum , Malaria , Diagnostic Tests, Routine/methods , Humans , Machine Learning , Malaria/diagnosis , Malaria/parasitology , Malaria, Falciparum/parasitology , Microscopy/methods , Parasitemia/diagnosis , Parasitemia/parasitology , Plasmodium falciparum , Reproducibility of Results , Sensitivity and Specificity
15.
Future Healthc J ; 9(1): 67-74, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35372781

ABSTRACT

With aspects of neurosurgery becoming increasingly digitised, there is a need to understand both the prevalence and impact of digital tools on clinical and organisational outcomes. Consequently, we sought to evaluate evidence of the use of digital tools in neurosurgical settings. We systematically searched three public databases for relevant articles: 283 articles were screened using inclusion/exclusion criteria, with 26 selected for further analysis. Many studies reported on the use of simulation, smartphones, telemedicine and robotics in neurosurgical pathways from education through to postoperative care. Though generally beneficial for both patient and organisational outcomes, a number of considerations were highlighted. Many referred to protection of patient data, cost and requirements to ensure socially disadvantaged groups are not further excluded by the move to digital services. Fortunately, with further innovation, many of these limitations look set to dissipate over coming years, paving the way for a more streamlined neurosurgical pathway.

16.
Appl Phys Lett ; 120(11): 114101, 2022 Mar 14.
Article in English | MEDLINE | ID: mdl-35355883

ABSTRACT

The nonlinear mechanical behavior of individual nanoscale collagen fibrils is governed by molecular stretching and sliding that result in a viscous response, which is still not fully understood. Toward this goal, the in vitro mechanical behavior of individual reconstituted mammalian collagen fibrils was quantified in a broad range of strain-rates, spanning roughly six orders of magnitude, from 10-4 to 35 s-1. It is shown that the nonlinear mechanical response is strain rate sensitive with the tangent modulus in the linear deformation regime increasing monotonically from 214 ± 8 to 358 ± 11 MPa. More pronounced is the effect of the strain rate on the ultimate tensile strength that is found to increase monotonically by a factor of four, from 42 ± 6 to 160 ± 14 MPa. Importantly, fibril strengthening takes place without a reduction in ductility, which results in equivalently large increase in toughness with the increasing strain rate. This experimental strain rate dependent mechanical response is captured well by a structural constitutive model that incorporates the salient features of the collagen microstructure via a process of gradual recruitment of kinked tropocollagen molecules, thus giving rise to the initial "toe-heel" mechanical behavior, followed by molecular stretching and sustained intermolecular slip that is initiated at a strain rate dependent stress threshold. The model shows that the fraction of tropocollagen molecules undergoing straightening increases continuously during loading, whereas molecular sliding is initiated after a small fibril strain (1%-2%) and progressively increases with applied strain.

17.
J Glaucoma ; 31(3): e1-e9, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35210385

ABSTRACT

PRCIS: NOTCH signaling is significantly upregulated in the lens capsules of eyes with pseudoexfoliation syndrome (PXF) but not in those with pseudoexfoliation glaucoma (PXG) when compared with healthy controls. PURPOSE: NOTCH signaling has neuroprotective functions and altered NOTCH signaling is associated with neurodegenerative diseases with protein aggregation such as Alzheimer disease. As PXG is also a protein aggregate disease associated with neural degeneration, NOTCH molecular expression was explored in the lens capsules of patients with PXF, PXG, primary open-angle glaucoma (POAG), and healthy controls. METHODS: Anterior lens capsules were collected from 106 patients (27 PXF, 24 PXG, 22 POAG, and 33 controls) undergoing cataract surgery. Gene expression profiling for NOTCH pathway molecules (ligands, receptors, and downstream target genes) was performed on the tissue using a quantitative reverse transcription-polymerase chain reaction. The results were confirmed by protein analysis using dot-blot or immunostaining techniques. RESULTS: There was no difference in the demographic characteristics between the groups. There was an increase in NOTCH4 receptor expression (>14-fold) in the PXF group as compared with the controls. Similarly, the Delta-like 3 and Delta-like 4 ligands were significantly elevated in the PXF group compared with controls (P<0.05). Downstream targets HES3, HES5, and HEY1 expression were significantly elevated (P<0.005) in PXF lens capsules, confirming a higher activity of NOTCH signaling in this cohort. Immunostaining also corroborated the gene expression profile. CONCLUSION: The finding that NOTCH signaling is significantly upregulated in the lens capsule of eyes with PXF and not in PXG or POAG patients suggests a possible protective role in the development of glaucoma.


Subject(s)
Exfoliation Syndrome , Glaucoma, Open-Angle , Glaucoma , Lens, Crystalline , Exfoliation Syndrome/complications , Glaucoma/complications , Glaucoma, Open-Angle/surgery , Humans , Intraocular Pressure
18.
Opt Lasers Eng ; 1502022 Mar.
Article in English | MEDLINE | ID: mdl-35027783

ABSTRACT

Nanoscale macromolecular biological structures exhibit time-dependent behavior, yet a quantitative understanding of their time-dependent mechanical behavior remains elusive, largely due to experimental challenges in attaining sufficient spatial and temporal resolution and control of stress or strain in conditions that guarantee their molecular integrity. To address this gap, an experimental methodology was developed to conduct creep and stress relaxation experiments with individual mammalian collagen fibrils. An image-based edge detection method implemented with high magnification optical microscopy and combined with closed-loop proportional-integral-derivative (PID) control was implemented and calibrated to apply constant force or stretch ratio values to individual collagen fibrils via a Microelectromechanical Systems (MEMS) device. This experimental methodology allowed for real-time control of uniaxial tensile stress or strain with 27 nm displacement resolution. The overall experimental system was tuned to apply step inputs with rise times below 0.5 s, less than 2.5% overshoot, and steady-state error less than 0.5%. Three individual collagen fibrils with diameters 101-121 nm were subjected to creep and stress relaxation tests in the range 4-20% engineering strain, under partially hydrated conditions. The collagen fibrils demonstrated non-linear viscoelastic behavior that was described well by the adaptive quasi-linear viscoelastic model. The results of this study demonstrate for the first time that mammalian collagen fibrils, the building blocks of connective tissues, exhibit nonlinear viscoelastic behavior in their partially hydrated state.

19.
Cytotherapy ; 24(3): 235-248, 2022 03.
Article in English | MEDLINE | ID: mdl-34656419

ABSTRACT

The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses a never before seen challenge to human health and the economy. Considering its clinical impact, with no streamlined therapeutic strategies in sight, it is crucial to understand the infection process of SARS-CoV-2. Our limited knowledge of the mechanisms underlying SARS-CoV-2 infection impedes the development of alternative therapeutics to address the pandemic. This aspect can be addressed by modeling SARS-CoV-2 infection in the human context to facilitate drug screening and discovery. Human induced pluripotent stem cell (iPSC)-derived lung epithelial cells and organoids recapitulating the features and functionality of the alveolar cell types can serve as an in vitro human model and screening platform for SARS-CoV-2. Recent studies suggest an immune system asynchrony leading to compromised function and a decreased proportion of specific immune cell types in coronavirus disease 2019 (COVID-19) patients. Replenishing these specific immune cells may serve as useful treatment modality against SARS-CoV-2 infection. Here the authors review protocols for deriving lung epithelial cells, alveolar organoids and specific immune cell types, such as T lymphocytes and natural killer cells, from iPSCs with the aim to aid investigators in making relevant in vitro models of SARS-CoV-2 along with the possibility derive immune cell types to treat COVID-19.


Subject(s)
COVID-19 , Induced Pluripotent Stem Cells , Humans , Induced Pluripotent Stem Cells/metabolism , Organoids/metabolism , Prospective Studies , SARS-CoV-2
20.
J Am Coll Cardiol ; 78(25): 2550-2560, 2021 12 21.
Article in English | MEDLINE | ID: mdl-34915986

ABSTRACT

BACKGROUND: Regional heart attack services have improved clinical outcomes following ST-segment elevation myocardial infarction (STEMI) by facilitating early reperfusion by primary percutaneous coronary intervention (PCI). Early discharge after primary PCI is welcomed by patients and increases efficiency of health care. OBJECTIVES: This study aimed to assess the safety and feasibility of a novel early hospital discharge pathway for low-risk STEMI patients. METHODS: Between March 2020 and June 2021, 600 patients who were deemed at low risk for early major adverse cardiovascular events (MACE) were selected for inclusion in the pathway and were successfully discharged in <48 hours. Patients were reviewed by a structured telephone follow-up at 48 hours after discharge by a cardiac rehabilitation nurse and underwent a virtual follow-up at 2, 6, and 8 weeks and at 3 months. RESULTS: The median length of hospital stay was 24.6 hours (interquartile range [IQR]: 22.7-30.0 hours) (prepathway median: 65.9 hours [IQR: 48.1-120.2 hours]). After discharge, all patients were contacted, with none lost to follow-up. During median follow-up of 271 days (IQR: 88-318 days), there were 2 deaths (0.33%), both caused by coronavirus disease 2019 (>30 days after discharge), with 0% cardiovascular mortality and MACE rates of 1.2%. This finding compared favorably with a historical group of 700 patients meeting pathway criteria who remained in the hospital for >48 hours (>48-hour control group) (mortality, 0.7%; MACE, 1.9%) both in unadjusted and propensity-matched analyses. CONCLUSIONS: Selected low-risk patients can be discharged safely following successful primary PCI by using a pathway that is supported by a structured, multidisciplinary virtual follow-up schedule.


Subject(s)
Length of Stay/statistics & numerical data , Patient Discharge , Percutaneous Coronary Intervention/statistics & numerical data , ST Elevation Myocardial Infarction/surgery , Aged , COVID-19/prevention & control , Critical Pathways , Female , Humans , Male , Middle Aged , Prospective Studies
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