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1.
Sci Rep ; 14(1): 19615, 2024 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-39179653

RESUMO

Electrospinning stands out as a flexible and viable method, presenting designed nanoscale materials with customized properties. This research demonstrates the immobilization of carboxylesterase protein Ha006a, reported for its adequacy in pesticide bioremediation by utilizing the electrospinning strategy. This strategy was utilized to create nanofibers by incorporating variable mixtures of biodegradable and cost-effective polyvinyl alcohol (PVA)-chitosan (CS) nanofiber solution (PVA100, PVA96, PVA94, PVA92 and PVA90). All the mixtures were electrospun at a reliable voltage of 21 kV, maintaining a gap of 12 cm from the nozzle. The Ha006a, sourced from Helicoverpa armigera, was consolidated into the optimized PVA90 polymer mixture. The electrospun nanofibers experienced comprehensive characterization utilizing distinctive microscopy and spectroscopy procedures counting FESEM, TGA, XRD and FTIR. The comparative investigation of the esterase property, ideal parameters and stability of the unbound and bound/immobilized Ha006a was scrutinized. The results uncovered an essential elevation in the ideal conditions of enzyme activity post-immobilization. The PVA-CS control nanofiber and Ha006a-PVA-CS showed a smooth structure, including an average breadth of around 170.5 ± 44.2 and 222.5 ± 66.5 nm, respectively. The enzyme-immobilized nanofibers displayed upgraded stability and comprehensive characterization of the nanofiber, which guaranteed genuineness and reproducibility, contributing to its potential as a potent device for bioremediation applications. This investigation opens the way for the manufacture of pesticide-resistant insect enzyme-based nanofibers, unlocking their potential for assorted applications, counting pesticide remediation and ensuring environmental sustainability.


Assuntos
Carboxilesterase , Quitosana , Estabilidade Enzimática , Enzimas Imobilizadas , Nanofibras , Álcool de Polivinil , Álcool de Polivinil/química , Nanofibras/química , Quitosana/química , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Carboxilesterase/metabolismo , Carboxilesterase/química , Animais , Concentração de Íons de Hidrogênio
2.
Cureus ; 16(6): e61512, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38957252

RESUMO

BACKGROUND: This study aims to assess the effectiveness of the chronic care model (CCM) in helping primary healthcare workers quit smoking. The intervention involves implementing the CCM, which includes six key elements: the healthcare system, clinical care planning, clinical management information, self-management guidance, community resources, and decision-making. MATERIAL AND METHODS: The study is based on a population of 60 primary healthcare workers who smoke. The main outcome measure is smoking cessation, determined by cotinine levels in urine at the baseline, and at 6 and 12 months after the intervention. Other potential results include alterations in smoking-related behaviors and attitudes. Data analysis involves using descriptive statistics and inferential tests to determine the intervention's effectiveness in smoking cessation among primary healthcare workers. RESULTS:  The CCM is expected to have contributed to a substantial decrease in the smoking rate among primary healthcare workers. It is also seen that there is a great reduction in urine cotinine levels during the 12-month intervention period. Moreover, a positive shift in the smoking-related behaviors and attitudes of the participants is expected. CONCLUSION:  This study provides key data about the effectiveness of the CCM in helping primary healthcare workers stop smoking. This statement emphasizes the importance of considering socioeconomic factors in the design and implementation of smoking cessation interventions. This ensures that people of different incomes and social statuses have equal access to quitting smoking and achieve similar results.

3.
Virus Res ; 345: 199384, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38702018

RESUMO

Due to the limited size of viral genomes, hijacking host machinery by the viruses taking place throughout the virus life cycle is inevitable for the survival and proliferation of the virus in the infected hosts. Recent reports indicated that Annexin A2 (AnxA2), a calcium- and lipid-binding cellular protein, plays an important role as a critical regulator in various steps of the virus life cycle. The multifarious AnxA2 functions in cells, such as adhesion, adsorption, endocytosis, exocytosis, cell proliferation and division, inflammation, cancer metastasis, angiogenesis, etc., are intimately related to the various clinical courses of viral infection. Ubiquitous expression of AnxA2 across multiple cell types indicates the broad range of susceptibility of diverse species of the virus to induce disparate viral disease in various tissues, and intracellular expression of AnxA2 in the cytoplasmic membrane, cytosol, and nucleus suggests the involvement of AnxA2 in the regulation of the different stages of various virus life cycles within host cells. However, it is yet unclear as to the molecular processes on how AnxA2 and the infected virus interplay to regulate virus life cycles and thereby the virus-associated disease courses, and hence elucidation of the molecular mechanisms on AnxA2-mediated virus life cycle will provide essential clues to develop therapeutics deterring viral disease.


Assuntos
Anexina A2 , Anexina A2/metabolismo , Anexina A2/genética , Humanos , Replicação Viral , Interações Hospedeiro-Patógeno , Animais , Viroses/metabolismo , Viroses/virologia , Vírus/genética , Vírus/metabolismo , Vírus/crescimento & desenvolvimento , Internalização do Vírus
4.
J Pharm Bioallied Sci ; 16(Suppl 1): S672-S674, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38595598

RESUMO

Objectives: To ascertain whether a link exists between vitamin D insufficiency and early childhood caries or not. Method: From the out patient department (OPD) of the Pedodontics Department at Vyas Dental College, a random sample of 40 kids between the ages of 8 months and 5 years old was chosen. Each kid had blood drawn to check their serum 25(OH) vitamin D levels. All of the data was collated and given the necessary statistical analysis. Result: The case group's mean serum 25(OH) vitamin D level was 10.19 ng/mL (with a standard deviation of 3.46), while the control group's was 20.84 ng/mL (2.54 SD). Conclusion: A significant modifiable risk factor for childhood dental caries is a vitamin D deficiency. Therefore, cavities in teeth can be avoided by giving youngsters vitamin D supplements and avoiding vitamin D insufficiency.

5.
Int J Radiat Oncol Biol Phys ; 118(4): 1105-1109, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37956734

RESUMO

PURPOSE: This study aimed to demonstrate for the first time the possibility of irradiating biological cells with gray (Gy)-scale doses delivered over single bursts of picosecond-scale electron beams, resulting in unprecedented dose rates of 1010 to 1011 Gy/s. METHODS AND MATERIALS: Cancer stem cells and human skin fibroblasts were irradiated with MeV-scale electron beams from a laser-driven source. Doses up to 3 Gy per pulse with a high spatial uniformity (coefficient of variance, 3%-6%) and within a timescale range of 10 to 20 picoseconds were delivered. Doses were characterized during irradiation and were found to be in agreement with Monte Carlo simulations. Cell survival and DNA double-strand break repair dynamics were studied for both cell lines using clonogenic assay and 53BP1 foci formation. The results were compared with reference x-rays at a dose rate of 0.49 Gy/min. RESULTS: Results from clonogenic assays of both cell lines up to 3 Gy were well fitted by a linear quadratic model with α = (0.68 ± 0.08) Gy-1 and ß = (0.01 ± 0.01) Gy-2 for human skin fibroblasts and α = (0.51 ± 0.14) Gy-1 and ß = (0.01 ± 0.01) Gy-2 for cancer stem cells. Compared with irradiation at 0.49 Gy/min, our experimental results indicate no statistically significant difference in cell survival rate for doses up to 3 Gy despite a significant increase in the α parameter, which may reflect more complex damage. Foci measurements showed no significant difference between irradiation at 1011 Gy/s and at 0.49 Gy/min. CONCLUSIONS: This study demonstrates the possibility of performing radiobiological studies with picosecond-scale laser-generated electron beams at ultrahigh dose rates of 1010 to1011 Gy/s. Preliminary results indicate, within statistical uncertainties, a significant increase of the α parameter, a possible indication of more complex damage induced by a higher density of ionizing tracks.


Assuntos
Elétrons , Neoplasias , Humanos , Relação Dose-Resposta à Radiação , Reparo do DNA , Fibroblastos/efeitos da radiação , Células-Tronco Neoplásicas , Neoplasias/metabolismo
6.
Inorg Chem ; 63(1): 714-729, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38150362

RESUMO

Ligands derived from 2-(1-phenylhydrazinyl)pyridine and salicylaldehyde (HL1), 3-methoxysalicylaldehyde (HL2), 5-bromosalicylaldehyde (HL3), and 3,5-di-tert-butylsalicylaldehyde (HL4) react with [VIVO(acac)2] in MeOH followed by aerial oxidation to give [VVO2(L1)] (1), [VVO2(L2)] (2), [VVO2(L3)] (3), and [VVO2(L4)] (4). Complex [VIVO(acac)(L1)] (5) is also isolable from [VIVO(acac)2] and HL1 in dry MeOH. Structures of all complexes were confirmed by single-crystal X-ray and spectroscopic studies. They efficiently catalyze benzyl alcohol and its derivatives' oxidation in the presence of H2O2 to their corresponding aldehydes. Under optimized reaction conditions using 1 as a catalyst precursor, conversion of benzyl alcohol follows the order: 4 (93%) > 2 (90%) > 1 (86%) > 3 (84%) ≈ 5 (84%). These complexes were also evaluated for antifungal and antiproliferative activities. Complex 3 with MIC50 = 16 µg/mL, 4 with MIC50 = 12 µg/mL, and 5 with MIC50 = 16 µg/mL are efficient toward planktonic cells of Candida albicans and Candida tropicalis. On Michigan cancer foundation-7 (MCF-7) cells, they show comparable cytotoxic effects and exhibit IC50 in the 27.3-33.5 µg/mL range, and among these, 4 exhibits the highest cytotoxicity. A similar study on human embryonic kidney cells (HEK293) confirms their less toxicity at lower concentrations (4 to 16 µg/mL) compared to MCF-7.


Assuntos
Antifúngicos , Vanádio , Humanos , Vanádio/química , Antifúngicos/farmacologia , Peróxido de Hidrogênio/química , Células HEK293 , Álcoois Benzílicos , Ligantes
7.
Virus Res ; 335: 199191, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37541588

RESUMO

The Ubiquitin-protein ligase E3A, UBE3A, also known as E6-associated protein (E6-AP), is known to play an essential role in regulating the degradation of various proteins by transferring Ub from E2 Ub conjugating enzymes to the substrate proteins. Several studies indicate that UBE3A regulates the stabilities of key viral proteins in the virus-infected cells and, thereby, the infected virus-mediated diseases, even if it were reported that UBE3A participates in non-viral-related human diseases. Furthermore, mutations such as deletions and duplications in the maternally inherited gene in the brain cause human neurodevelopmental disorders such as Angelman syndrome (AS) and autism. It is also known that UBE3A functions as a transcriptional coactivator for the expression of steroid hormone receptors. These reports establish that UBE3A is distinguished by its multitudinous functions that are paramount to viral pathology and human diseases. This review is focused on molecular mechanisms for such intensive participation of UBE3A in disease formation and virus regulation.


Assuntos
Síndrome de Angelman , Viroses , Humanos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Mutação , Encéfalo/patologia , Síndrome de Angelman/genética , Síndrome de Angelman/metabolismo , Síndrome de Angelman/patologia , Viroses/genética
8.
Eur J Pediatr ; 182(8): 3701-3711, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37278737

RESUMO

Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group, three-arm assessor-blinded randomized controlled trial compared the effects of three different timings of DCC at 30, 60, and 120 s on venous hematocrit and serum ferritin levels in late preterm and term neonates not requiring resuscitation. Eligible newborns (n = 204) were randomized to DCC 30 (n = 65), DCC 60 (n = 70), and DCC 120 (n = 69) groups immediately after delivery. The primary outcome variable was venous hematocrit at 24 ± 2 h. Secondary outcome variables were respiratory support, axillary temperature, vital parameters, incidences of polycythemia, neonatal hyperbilirubinemia (NNH), need and duration of phototherapy, and postpartum hemorrhage (PPH). Additionally, serum ferritin levels, the incidence of iron deficiency, exclusive breastfeeding (EBF) rate, and anthropometric parameters were assessed during post-discharge follow-up at 12 ± 2 weeks. Over one-third of the included mothers were anemic. DCC 120 was associated with a significant increase in the mean hematocrit by 2%, incidence of polycythemia, and duration of phototherapy, compared to DCC30 and DCC60; though the incidence of NNH and need for phototherapy was similar. No other serious neonatal or maternal adverse events including PPH were observed. No significant difference was documented in serum ferritin, incidences of iron deficiency, and growth parameters at 3 months even in the presence of a high EBF rate.   Conclusion: The standard recommendation of DCC at 30-60 s may be considered a safe and effective intervention in the busy settings of low-middle-income countries with a high prevalence of maternal anemia.   Trial registration: Clinical trial registry of India (CTRI/2021/10/037070). What is Known: • The benefits of delayed cord clamping (DCC) makes it an increasingly well-accepted practice in the delivery room. • However, uncertainty continues regarding the optimal timing of clamping; this may be of concern both in the neonate and the mother. What is New: • DCC at 120 s led to higher hematocrit, polycythemia and longer duration of phototherapy, without any difference in serum ferritin, and incidence of iron deficiency. • DCC at 30-60 s may be considered a safe and effective intervention in LMICs.


Assuntos
Anemia , Hiperbilirrubinemia Neonatal , Deficiências de Ferro , Policitemia , Gravidez , Feminino , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Policitemia/etiologia , Policitemia/terapia , Assistência ao Convalescente , Clampeamento do Cordão Umbilical , Alta do Paciente , Constrição , Ferritinas , Cordão Umbilical , Parto Obstétrico/efeitos adversos
10.
Am J Cancer Res ; 13(3): 1082-1090, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37034219

RESUMO

Among the innate immune cells, natural killer cells (NK) serve its role in cytolytic targeting against infected and cancerous cells. NK function is regulated by an intricate balance of signals from interactions between activating and inhibitory NK receptors and ligands expressed on target cells. As an immune evasion strategy, cancer cells, particularly triple-negative breast cancer cells (TNBCs), express ligands that interact with NK receptors to inhibit NK cell cytolytic function. Our studies have revealed that Proliferating Cell Nuclear Antigen (PCNA), normally expressed in the nucleus with DNA replication and repair roles, was present on the cell surface of TNBC cell lines MDA-MB-231, -436, and -468. To elucidate the function of cell surface PCNA, we blocked PCNA on TNBCs with antibodies which both disrupted interaction with NKp44 and enhanced lysis by primary NK cells. Furthermore, a combinational antibody treatment of TNBCs with α-LLT1 and α-PCNA antibodies augments NK-mediated lysis. These results together suggest that cell surface PCNA on TNBCs enables evasion from cytolytic killing by NK cells. Blocking PCNA-NKp44 interaction with antibodies may potentially open an additional avenue in treatment of TNBCs.

11.
Pharmaceutics ; 15(2)2023 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-36839766

RESUMO

Lung metastasis is a leading cause of cancer-related deaths. Here, we show that intranasal delivery of our engineered CpG-coated tumor antigen (Tag)-encapsulated nanoparticles (NPs)-nasal nano-vaccine-significantly reduced lung colonization by intravenous challenge of an extra-pulmonary tumor. Protection against tumor-cell lung colonization was linked to the induction of localized mucosal-associated effector and resident memory T cells as well as increased bronchiolar alveolar lavage-fluid IgA and serum IgG antibody responses. The nasal nano-vaccine-induced T-cell-mediated antitumor mucosal immune response was shown to increase tumor-specific production of IFN-γ and granzyme B by lung-derived CD8+ T cells. These findings demonstrate that our engineered nasal nano-vaccine has the potential to be used as a prophylactic approach prior to the seeding of tumors in the lungs, and thereby prevent overt lung metastases from existing extra pulmonary tumors.

13.
Phys Med Biol ; 68(2)2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36625355

RESUMO

Objective.Carbon is an ion species of significant radiobiological interest, particularly in view of its use in cancer radiotherapy, where its large Relative Biological Efficiency is often exploited to overcome radio resistance. A growing interest in highly pulsed carbon delivery has arisen in the context of the development of the FLASH radiotherapy approach, with recent studies carried out at dose rates of 40 Gy s-1. Laser acceleration methods, producing ultrashort ion bursts, can now enable the delivery of Gy-level doses of carbon ions at ultra-high dose rates (UHDRs), exceeding 109Gy s-1. While studies at such extreme dose rate have been carried out so far using low LET particles such as electrons and protons, the radiobiology of high-LET, UHDR ions has not yet been explored. Here, we report the first application of laser-accelerated carbon ions generated by focussing 1020W cm-2intense lasers on 10-25 nm carbon targets, to irradiate radioresistant patient-derived Glioblastoma stem like cells (GSCs).Approach.We exposed GSCs to 1 Gy of 9.5 ± 0.5 MeV/n carbon ions delivered in a single ultra-short (∼400-picosecond) pulse, at a dose rate of 2 × 109Gy s-1, generated using the ASTRA GEMINI laser of the Central Laser Facility at the Rutherford Appleton Laboratory, Didcot, Oxfordshire, UK. We quantified carbon ion-induced DNA double strand break (DSB) damage using the 53BP1 foci formation assay and used 225 kVp x-rays as a reference radiation.Main Results.Laser-accelerated carbon ions induced complex DNA DSB damage, as seen through persistent 53BP1 foci (11.5 ± 0.4 foci/cell/Gy) at 24 h and significantly larger foci (1.69 ± 0.07µm2) than x-rays induced ones (0.63 ± 0.02µm2). The relative foci induction value for laser-driven carbon ions relative to conventional x-rays was 3.2 ± 0.3 at 24 h post-irradiation also confirming the complex nature of the induced damage.Significance.Our study demonstrates the feasibility of radiobiology investigations at unprecedented dose rates using laser-accelerated high-LET carbon ions in clinically relevant models.


Assuntos
Quebras de DNA de Cadeia Dupla , Prótons , Humanos , Células Cultivadas , Íons , DNA , Lasers , Carbono/uso terapêutico
14.
Int J Radiat Oncol Biol Phys ; 116(4): 916-926, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-36642109

RESUMO

PURPOSE: In proton therapy, the clinical application of linear energy transfer (LET) optimization remains contentious, in part because of challenges associated with the definition and calculation of LET and its exact relationship with relative biological effectiveness (RBE) because of large variation in experimental in vitro data. This has raised interest in other metrics with favorable properties for biological optimization, such as the number of proton track ends in a voxel. In this work, we propose a novel model for clinical calculations of RBE, based on proton track end counts. METHODS AND MATERIALS: We developed an effective dose concept to translate between the total proton track-end count per unit mass in a voxel and a proton RBE value. Dose, track end, and dose-averaged LET (LETd) distributions were simulated using Monte Carlo models for a series of water phantoms, in vitro radiobiological studies, and patient treatment plans. We evaluated the correlation between track ends and regions of elevated biological effectiveness in comparison to LETd-based models of RBE. RESULTS: Track ends were found to correlate with biological effects in in vitro experiments with an accuracy comparable to LETd. In patient simulations, our track end model identified the same biological hotspots as predicted by LETd-based radiobiological models of proton RBE. CONCLUSIONS: These results suggest that, for clinical optimization and evaluation, an RBE model based on proton track end counts may match LETd-based models in terms of information provided while also offering superior statistical properties.


Assuntos
Terapia com Prótons , Prótons , Humanos , Eficiência Biológica Relativa , Planejamento da Radioterapia Assistida por Computador/métodos , Terapia com Prótons/métodos , Transferência Linear de Energia , Método de Monte Carlo
15.
Pharmaceuticals (Basel) ; 17(1)2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38256885

RESUMO

A hallmark of effective cancer treatment is the prevention of tumor reoccurrence and metastasis to distal organs, which are responsible for most cancer deaths. However, primary tumor resection is expected to be curative as most solid tumors have been shown both experimentally and clinically to accelerate metastasis to distal organs including the lungs. In this study, we evaluated the efficacy of our engineered nasal nano-vaccine (CpG-NP-Tag) in reducing accelerated lung metastasis resulting from primary tumor resection. Cytosine-phosphate-guanine oligonucleotide [CpG ODN]-conjugated nanoparticle [NP] encapsulating tumor antigen [Tag] (CpG-NP-Tag) was manufactured and tested in vivo using a syngeneic mouse mammary tumor model following intranasal delivery. We found that our nasal nano-vaccine (CpG-NP-Tag), compared to control NPs administered after primary mammary tumor resection, significantly reduced lung metastasis in female BALB/c mice subjected to surgery (surgery mice). An evaluation of vaccine efficacy in both surgery and non-surgery mice revealed that primary tumor resection reduces CD11b+ monocyte-derived suppressor-like cell accumulation in the lungs, allowing increased infiltration of vaccine-elicited T cells (IFN-γ CD8+ T cells) in the lungs of surgery mice compared to non-surgery mice. These findings suggest that the combination of the target delivery of a nasal vaccine in conjunction with the standard surgery of primary tumors is a plausible adjunctive treatment against the establishment of lung metastasis.

16.
Cancers (Basel) ; 14(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36428758

RESUMO

In this study, we aim to evaluate the significance of AnxA2 in BLCA and establish its metastatic role in bladder cancer cells. Analysis of TCGA data showed that AnxA2 mRNA expression was significantly higher in BLCA tumors than in normal bladder tissues. High mRNA expression of AnxA2 in BLCA was significantly associated with high pathological grades and stages, non-papillary tumor histology, and poor overall survival (OS), progression-free survival (PFS), and diseases specific survival (DSS). Similarly, we found that AnxA2 expression was higher in bladder cancer cells derived from high-grade metastatic carcinoma than in cells derived from low-grade urothelial carcinoma. AnxA2 expression significantly mobilized to the surface of highly metastatic bladder cancer cells compared to cells derived from low-grade tumors and associated with high plasmin generation and AnxA2 secretion. In addition, the downregulation of AnxA2 cells significantly inhibited the proliferation, migration, and invasion in bladder cancer along with the reduction in proangiogenic factors and cytokines such as PDGF-BB, ANGPT1, ANGPT2, Tie-2, bFGF, GRO, IL-6, IL-8, and MMP-9. These findings suggest that AnxA2 could be a promising biomarker and therapeutic target for high-grade BLCA.

17.
J Fungi (Basel) ; 8(9)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36135680

RESUMO

Clinically diagnosing fungal keratitis (FK) is challenging; diagnosis can be assisted by investigations including in vivo confocal microscopy (IVCM), smear microscopy, and culture. The aim of this study was to estimate the sensitivity in detecting fungal keratitis (FK) using IVCM, smear microscopy, and culture in a setting with a high prevalence of FK. In this cross-sectional study nested within a prospective cohort study, consecutive microbial keratitis (MK) patients attending a tertiary-referral eye hospital in south-eastern Nepal between June 2019 and November 2020 were recruited. IVCM and corneal scrapes for smear microscopy and culture were performed using a standardised protocol. Smear microscopy was performed using potassium hydroxide (KOH), Gram stain, and calcofluor white. The primary outcomes were sensitivities with 95% confidence intervals [95% CI] for IVCM, smear microscopy and culture, and for each different microscopy stain independently, to detect FK compared to a composite referent. We enrolled 642 patients with MK; 468/642 (72.9%) were filamentous FK, 32/642 (5.0%) were bacterial keratitis and 64/642 (10.0%) were mixed bacterial-filamentous FK, with one yeast infection (0.16%). No organism was identified in 77/642 (12.0%). Smear microscopy had the highest sensitivity (90.7% [87.9-93.1%]), followed by IVCM (89.8% [86.9-92.3%]) and culture (75.7% [71.8-79.3%]). Of the three smear microscopy stains, KOH had the highest sensitivity (85.3% [81.9-88.4%]), followed by Gram stain (83.2% [79.7-86.4%]) and calcofluor white (79.1% [75.4-82.5%]). Smear microscopy and IVCM were the most sensitive tools for identifying FK in our cohort. In low-resource settings we recommend clinicians perform corneal scrapes for microscopy using KOH and Gram staining. Culture remains an important tool to diagnose bacterial infection, identify causative fungi and enable antimicrobial susceptibility testing.

18.
Front Med (Lausanne) ; 9: 915293, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935768

RESUMO

Background: The aim of this study was to describe the health-seeking journey for patients with microbial keratitis (MK) in Nepal and identify factors associated with delay. Methods: Prospective cohort study where MK patients attending a large, tertiary-referral eye hospital in south-eastern Nepal between June 2019 and November 2020 were recruited. We collected demographic details, clinical history, and examination findings. Care-seeking journey details were captured including places attended, number of journeys, time from symptom onset, and costs. We compared "direct" with "indirect" presenters, analyzing for predictors of delay. Results: We enrolled 643 patients with MK. The majority (96%) self-referred. "Direct" attenders accounted for only 23.6% (152/643) of patients, the majority of "indirect" patients initially presented to a pharmacy (255/491). Over half (328/643) of all cases presented after at least 7 days. The total cost of care increased with increasing numbers of facilities visited (p < 0.001). Those living furthest away were least likely to present directly (p < 0.001). Factors independently associated with delayed presentation included distance >50 km from the eye hospital [aOR 5.760 (95% CI 1.829-18.14, p = 0.003)], previous antifungal use [aOR 4.706 (95% CI 3.139-5.360)], and two or more previous journeys [aOR 1.442 (95% CI 1.111-3.255)]. Conclusions: Most patients visited at least one facility prior to our institution, with time to presentation and costs increasing with the number of prior journeys. Distance to the eye hospital is a significant barrier to prompt, direct presentation. Based on these findings, improving access to eye care services, strengthening referral networks and encouraging early appropriate treatment are recommended to reduce delay, ultimately improving clinical outcomes.

20.
Cells ; 11(14)2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35883618

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an enveloped, positive sense, single stranded RNA (+ssRNA) virus, belonging to the genus Betacoronavirus and family Coronaviridae. It is primarily transmitted from infected persons to healthy ones through inhalation of virus-laden respiratory droplets. After an average incubation period of 2-14 days, the majority of infected individuals remain asymptomatic and/or mildly symptomatic, whereas the remaining individuals manifest a myriad of clinical symptoms, including fever, sore throat, dry cough, fatigue, chest pain, and breathlessness. SARS-CoV-2 exploits the angiotensin converting enzyme 2 (ACE-2) receptor for cellular invasion, and lungs are amongst the most adversely affected organs in the body. Thereupon, immune responses are elicited, which may devolve into a cytokine storm characterized by enhanced secretion of multitude of inflammatory cytokines/chemokines and growth factors, such as interleukin (IL)-2, IL-6, IL-7, IL-8, IL-9, tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (GCSF), basic fibroblast growth factor 2 (bFGF2), monocyte chemotactic protein-1 (MCP1), interferon-inducible protein 10 (IP10), macrophage inflammatory protein 1A (MIP1A), platelet-derived growth factor subunit B (PDGFB), and vascular endothelial factor (VEGF)-A. The systemic persistence of inflammatory molecules causes widespread histological injury, leading to functional deterioration of the infected organ(s). Although multiple treatment modalities with varying effectiveness are being employed, nevertheless, there is no curative COVID-19 therapy available to date. In this regard, one plausible supportive therapeutic modality may involve administration of mesenchymal stem cells (MSCs) and/or MSC-derived bioactive factors-based secretome to critically ill COVID-19 patients with the intention of accomplishing better clinical outcome owing to their empirically established beneficial effects. MSCs are well established adult stem cells (ASCs) with respect to their immunomodulatory, anti-inflammatory, anti-oxidative, anti-apoptotic, pro-angiogenic, and pro-regenerative properties. The immunomodulatory capabilities of MSCs are not constitutive but rather are highly dependent on a holistic niche. Following intravenous infusion, MSCs are known to undergo considerable histological trapping in the lungs and, therefore, become well positioned to directly engage with lung infiltrating immune cells, and thereby mitigate excessive inflammation and reverse/regenerate damaged alveolar epithelial cells and associated tissue post SARS-CoV-2 infection. Considering the myriad of abovementioned biologically beneficial properties and emerging translational insights, MSCs may be used as potential supportive therapy to counteract cytokine storms and reduce disease severity, thereby facilitating speedy recovery and health restoration.


Assuntos
COVID-19 , Células-Tronco Mesenquimais , Adulto , COVID-19/terapia , Síndrome da Liberação de Citocina , Humanos , Imunidade , Imunomodulação , Células-Tronco Mesenquimais/metabolismo , SARS-CoV-2
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