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This study is conducted to observe the association of diabetes (DM), hypertension (HTN) and chronic kidney disease (CKD) on the prognosis and mortality of COVID-19 infection in hospital admitted patients with above mentioned comorbidities. This is a single centre, observational, retrospective study carried out at Sir Ganga Ram Hospital, Delhi, India. The burden of comorbidities on the prognosis and clinical outcome of COVID-19 patients admitted patients from April 8, 2020, to October 4, 2020. Chi-square and relative risk test were used to observe the association of comorbidities and disease prognosis. A total of 2586 patients were included in the study consisting of 69.6% of male patients. All the comorbidities were significantly associated with ICU admission and mortality. The relative risk showed that CKD is most prone to severity as well as mortality of the COVID-19 infection followed by HTN and DM. Further with the increase in number of underlying comorbidities, the risk of ICU admission and mortality also increases. Relative risk of the severity of COVID-19 infection in younger patients with underlying comorbidities are relatively at higher risk of severity of disease as well as to mortality compared to the elderly patients with similar underlying condition. Similarly, it is found that females are relatively at higher risk of mortality as compared to the males having same comorbid conditions except for the hypertensive patients. Diabetes, hypertension and CKD, all are associated with progression of COVID-19 disease to severity and higher mortality risk. The number of underlying comorbid condition is directly proportional to the progression of disease severity and mortality.
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COVID-19 , Diabetes Mellitus , Hipertensión , Insuficiencia Renal Crónica , Femenino , Humanos , Masculino , Anciano , COVID-19/epidemiología , Estudios Retrospectivos , SARS-CoV-2 , Factores de Riesgo , Diabetes Mellitus/epidemiología , Hipertensión/complicaciones , Hipertensión/epidemiología , Insuficiencia Renal Crónica/epidemiologíaRESUMEN
A Gram-stain-positive, spore-forming bacterium, EAG3T, capable of growing on 3-nitropropionic acid as the sole source of carbon, nitrogen and energy, was isolated from the anterior gut of an earthworm (Eisenia fetida) reared at the Centre of Floriculture and Agribusiness Management of the University of North Bengal at Siliguri (26.7072° N, 88.3558° E), West Bengal, India. The DNA G+C content of strain EAG3T was 42.5 mol%. Strain EAG3T contained MK-7 and MK-8 as predominant menaquinones. The predominant polar lipids were phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine. The major cellular fatty acids were 13-methyltetradecanoic acid, (9Z)-9-hexadecen-1-ol, 12-methyltetradecanoic acid and 14-methylpentadecanoic acid. The draft genome of strain EAG3T, distributed in 57 contigs, was found to be 3.8 Mb. A total of 3811 potential coding sequences or genes were predicted, including 3672 protein-coding and 108 RNA-coding ones together with 31 pseudogenes. One hundred and thirty-five genes encoded hypothetical proteins with no meaningful homologies with known proteins. The EAG3T genome encompassed two nitronate monooxygenase and one methylmalonate-semialdehyde dehydrogenase (CoA acylating) homologues. 16S rRNA gene sequence-based phylogeny revealed that the closest relative of strain EAG3T was Bacillus methanolicus NCIMB 13113T (95.7â% similarity). Phylogenetic, physiological and biochemical characteristics differentiated strain EAG3T from B. methanolicus, as well as from the other close taxonomic relatives Planococcus rifietoensis M8T, Bhargavaea cecembensis DSE10T, Planomicrobium flavidum ISL-41Tand Fermentibacilluspolygoni IEB3T, with which strain EAG3T had 93.3-94.2â% 16S rRNA gene sequence similarities. The new isolate, therefore, was considered as representing a novel genus of family Bacillaceae, for which the name Pradoshia eiseniae gen. nov., sp. nov. is proposed, with EAG3T (=LMG 30312T=JCM 32460T) as the type strain.
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Bacillaceae/clasificación , Nitrocompuestos/metabolismo , Oligoquetos/microbiología , Filogenia , Propionatos/metabolismo , Animales , Bacillaceae/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Genoma Bacteriano , India , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
Background & objectives: : Nucleic acid amplification test (NAT) in blood donor screening not only detects window period (WP) donors but also those with chronic occult infections which are negative by routine serological screening. This study was conducted to determine the time trend of NAT positivity and seroprevalence of transfusion-transmitted infections (TTIs) through a period of six years and evaluate the strength of NAT as a supplementary test in identifying the cryptic carriers in blood donor population. Methods: : A total of 1,01,411 blood donations were screened between January 2011 and December 2016 by the ELISA and individual donor (ID) NAT Procleix Ultrio Plus Assay. Additional molecular and serological assays were done on the NAT yield samples to differentiate the type of cryptic carriers. Results: : NAT yields comprised 0.05 per cent (50/101411) of the total samples tested with a yield rate of 1/2028. Hepatitis B virus (HBV) contributed to 80 per cent of the total NAT yields and the rest 20 per cent due to hepatitis C virus (HCV). Majority of HBV NAT yields (75%) were from chronic occult donors and 25 per cent were WP donors. Both HBV and HCV NAT yields had a wide range of viral count. There was no HIV NAT yield. A significant decline in the prevalence rate of TTIs through the study period of six years was observed. Interpretation & conclusions: : The cryptic infections found in blood donors increase the risk of TTIs. Blood screening by both serology and NAT can reduce this threat.
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Antígenos de Superficie de la Hepatitis B/sangre , Técnicas de Amplificación de Ácido Nucleico/métodos , Estudios Seroepidemiológicos , Reacción a la Transfusión/sangre , Adulto , Pueblo Asiatico , Donantes de Sangre , Seguridad de la Sangre , ADN Viral/genética , ADN Viral/aislamiento & purificación , Femenino , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepacivirus/patogenicidad , Hepatitis B/sangre , Hepatitis B/epidemiología , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis B/patogenicidad , Hepatitis C/sangre , Hepatitis C/epidemiología , Hepatitis C/virología , Humanos , India/epidemiología , Masculino , Reacción a la Transfusión/epidemiología , Reacción a la Transfusión/genética , Reacción a la Transfusión/virologíaRESUMEN
In this study, we demonstrate the feasibility of rapid volumetric additive manufacturing in the solid state. This additive manufacturing technology is particularly useful in outer space missions (microgravity) and/or for harsh environment (e.g., on ships and vehicles during maneuvering, or on airplanes during flight). A special thermal gel is applied here to demonstrate the concept, that is, ultraviolet crosslinking in the solid state. The produced hydrogels are characterized and the water-content-dependent heating/cooling/water-responsive shape memory effect is revealed. Here, the shape memory feature is required to eliminate the deformation induced in the process of removing the uncrosslinked part from the crosslinked part in the last step of this additive manufacturing process.
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BACKGROUND: Pulmonary hypertension (PH) is the abnormal elevation of pressure in the pulmonary vascular system, with various underlying causes. A specific type of PH is pulmonary arterial hypertension (PAH), a severe condition characterized by high pulmonary arterial pressure resulting from structural changes in distal pulmonary vessels, altered arterial tone, and inflammation. This leads to right ventricular hypertrophy and heart failure. The molecular mechanisms behind PAH are not well understood. This manuscript aims to elucidate these mechanisms using the genetic tool, aiding in diagnosis and treatment selection. METHOD: In our present study, we have obtained blood samples from both patients with pulmonary arterial hypertension (PAH) and healthy individuals. We conducted a comparative transcriptome analysis to identify genes that are either upregulated or downregulated in PAH patients when compared to the control group. Subsequently, we carried out a validation study focusing on the log2-fold downregulated genes in PAH, employing Quantitative Real-Time PCR for confirmation. Additionally, we quantified the proteins encoded by the validated genes using the ELISA technique. RESULTS: The results of the transcriptome analysis revealed that 97 genes were significantly upregulated, and 6 genes were significantly downregulated. Among these, we chose to focus on and validate only four of the downregulated genes, as they were directly or indirectly associated with the hypertension pathway. We also conducted validation studies for the proteins encoded by these genes, and the results were consistent with those obtained in the transcriptome analysis. CONCLUSION: In conclusion, the findings of this study indicate that the four validated genes identified in the context of PAH can be further explored as potential targets for both diagnostic and therapeutic applications.
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Regulación hacia Abajo , Perfilación de la Expresión Génica , Hipertensión Arterial Pulmonar , Humanos , Femenino , Masculino , Hipertensión Arterial Pulmonar/genética , Hipertensión Arterial Pulmonar/fisiopatología , India , Persona de Mediana Edad , Adulto , Transcriptoma , Regulación hacia Arriba , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/fisiopatología , Estudios de Casos y ControlesRESUMEN
Background and Aims: Ultrasound-guided transversus abdominis plane (TAP) block is an effective technique for postoperative analgesia in lower abdominal surgeries. This study aims to compare the duration and efficacy of an ultrasound-guided TAP block with those of a caudal epidural for paediatric unilateral lower abdominal surgeries. Methods: After ethical approval, sixty children aged 1 to 9 years were randomised into ultrasound-guided TAP block or caudal block with general anaesthesia for unilateral lower abdominal surgeries. The primary endpoint was time for the first rescue analgesia in the postoperative period. The secondary endpoints were total postoperative opioid consumption, modified Children Hospital of Eastern Ontario Pain Scale (CHEOPS) and the Face, Legs, Activity, Cry and Consolability (FLACC) scale in the postoperative period. Results: The mean time for first rescue analgesia was 11.33 ± 2.80 h in the TAP block group, while in the caudal group, it was 13.18 ± 2.67 h (95% confidence interval [CI] mean difference 2.58-10.58, P = 0.017). The total postoperative morphine requirement was comparable in both groups at both 12 h (TAP block group 0.50 ± 0.12 mg vs. caudal block group 0.56 ± 0.12 mg, 95% CI mean difference 0.09-0.02, P = 0.08) and 24 h (TAP block group 0.96 ± 0.30 mg vs. caudal block group 0.81 ± 0.34 mg, 95% CI mean difference 0.06-0.32, P = 0.06) time period. Conclusion: The mean time for first rescue analgesia was lesser in the TAP block group as compared to caudal group.
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The 2022 Monkeypox virus, an evolved DNA strain originating in Africa, exhibits heightened human-to-human transmissibility and potential animal transmission. Its host remains unidentified. While its initial slow transmission rate restrained global impact, 2022 saw a surge in cases, causing widespread concern in over 103 countries by September. This virus's distinctive human-to-human transmission marks a crucial shift, demanding a prompt revaluation of containment strategies. However, the host source for this shift requires urgent research attention. Regrettably, no universal preventive or curative methods have emerged for this evolved virus. Repurposed from smallpox vaccines, only some vaccinations offer a partial defense. Solely one therapeutic drug is available. The article's essence is to provide a comprehensive grasp of the virus's epidemiology, morphology, immune invasion mechanisms, and existing preventive and treatment measures. This knowledge equips researchers to devise strategies against its spread and potential public health implications.
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Mpox , Aceites Volátiles , Animales , Humanos , Mpox/epidemiología , Mpox/prevención & control , Brotes de Enfermedades/prevención & control , Salud Pública , ÁfricaRESUMEN
Background: ABO and Rh blood group systems are associated with many diseases including cancerous, infectious, non-infectious, bacterial and viral diseases. Studies have shown association of blood groups A and O with higher and lower odds for coronavirus disease 2019 positivity, respectively. Methods: This is a single-center, retrospective study conducted at Sir Ganga Ram Hospital, Delhi. We investigated the association of ABO and Rh blood groups with susceptibility to coronavirus disease 2019 infection, severity of disease, recovery period, and mortality of patients. Patients were enrolled from April 8, 2020 to October 4, 2020. A total of 2,586 real-time PCR (RT-PCR)-confirmed coronavirus disease 2019 (COVID-19) patients were recruited. Data was analyzed using chi-square test, odds ratio, and Mann-Whitney test to determine the association of blood groups. Results: In the 2,586 COVID-19-infected patients, the frequencies of A, B, O, and AB were 29.93%, 41.80%, 21.19%, and 7.98%, respectively. Of the patients, 98.07% were Rh positive. Blood group A (odds ratio, 1.53; CI, 1.40-1.66; p < 0.001) and B (odds ratio, 1.15; CI, 1.06-1.24; p < 0.001) is observed to be significantly associated with COVID-19 susceptibility, whereas blood group O (odds ratio, 0.65; CI, 0.59-0.71; p < 0.001) and AB (odds ratio, 0.66; CI, 0.59-0.71; p < 0.001) have low risk of COVID-19 infection. Conclusion: A, B, and Rh+ are found to be more susceptible to COVID-19 infection, whereas blood groups O, AB, and Rh- are at a lower risk of COVID-19 infection. No association was found between blood groups and susceptibility to severity of disease and mortality.
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COVID-19 , Sistema del Grupo Sanguíneo ABO/genética , Hospitales , Humanos , India/epidemiología , Estudios Retrospectivos , SARS-CoV-2RESUMEN
In this study, we report a high incidence of New Delhi metallo-ß-lactamase (NDM)-producing and ampicillin-catabolizing bacteria within carbapenem-resistant bacterial populations in the waters of two important rivers, Mahananda and Karala, bisecting two most populous towns, Siliguri and Jalpaiguri, respectively, in the northern West Bengal, India. Isolates producing NDM belonged to four genera, Acinetobacter, Escherichia, Proteus, and Pseudomonas; among which few were phylogenetically determined as putatively novel species. Class 1 integrons with the frequent presence of aadA and aac(6')-Ib gene cassettes in 50% of NDM-bearing isolates are indicative of possible selective pressures generated out of unregulated use of streptomycin, in agriculture practiced by the cultivators and tea planters living in locales drained by these two rivers, in their up- and downstream, and amikacin in the most crowded government-sponsored "sadar" and district hospitals of Siliguri and Jalpaiguri. NDM-delivering bacteria in rivers have genuine consequences for city inhabitants who are dependent on public water and sanitation facilities. Standard reconnaissance of antibiotic resistance, consolidating ecological sampling just as the assessment of clinical isolates, should be set up as a need.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/genética , Ríos/microbiología , beta-Lactamasas/genética , Acinetobacter/efectos de los fármacos , Escherichia/efectos de los fármacos , Genes Bacterianos , India , Integrones , Pruebas de Sensibilidad Microbiana , Proteus/efectos de los fármacos , Pseudomonas/efectos de los fármacosRESUMEN
OBJECTIVES: This study aims to investigate ampicillin catabolism in a pandrug-resistant strain, Pseudomonas sp. MR 02 of P. putida lineage. METHODS: The characterization of carbapenem resistance was done following the standard protocol. The broth macrodilution method was used to determine the MIC values of antimicrobial agents both in the presence and in the absence of phenylalanine-ß-naphthylamide. High MIC values (>10 000 mg/L) of ampicillin led to speculation that it may serve as a growth substrate, and thus minimal medium was used to evaluate ampicillin as a nutrient. The growth of MR 02 was measured in minimal medium in the presence or absence of 0.4 mM EDTA, supplemented with ampicillin as sole carbon, nitrogen and energy source. RNA-seq was used to generate expression profiles of genes in ampicillin or glucose-grown cells. The blaNDM-1 gene of MR 02 was cloned in the pHSG398 vector and expressed in Escherichia coli DH5α. RESULTS: Phenotypic analysis along with genome sequence data identifies Pseudomonas sp. MR 02 as a pandrug-resistant strain. Transcriptome data has revealed that blaNDM-1 was among the top 50 differentially expressed genes in ampicillin grown cells compared to the glucose grown cells in the minimal medium. Heterologous expression of blaNDM-1 gene in E. coli DH5α enabled its growth and subsistence on ampicillin as the sole source of carbon and energy. DISCUSSION: The ability of a pandrug-resistant Pseudomonas sp. MR 02 to consume ampicillin for growth has a huge implication in the bioremediation of ß-lactam residues in the environment.
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Ampicilina/metabolismo , Farmacorresistencia Bacteriana Múltiple , Pseudomonas/efectos de los fármacos , Pseudomonas/metabolismo , beta-Lactamasas/metabolismo , Antibacterianos/metabolismo , Antibacterianos/farmacología , Regulación Bacteriana de la Expresión Génica/fisiología , Regulación Enzimológica de la Expresión Génica/fisiología , Pruebas de Sensibilidad Microbiana , Pseudomonas/genética , beta-Lactamasas/genéticaRESUMEN
Electroconductive and injectable hydrogels are attracting increasing attention owing to the needs of electrically induced regulation of cell behavior, tissue engineering of electroactive tissues, and achieving minimum invasiveness during tissue repair. In this study, a novel in situ formed 3D conductive and cell-laden hydrogel is developed, which can be broadly used in bioprinting, tissue engineering, neuroengineering etc. An instantaneous, uniform spatial distribution and encapsulation of cells can be achieved as a result of hydrogen bonding induced hydrogel formation. Particularly, the cell-laden hydrogel can be easily obtained by simply mixing and shaking the polydopamine (PDA) functionalized rGO (rGO-PDA) with polyvinyl alcohol (PVA) solution containing cells. Graphene oxide is reduced and functionalized by dopamine to restore the electrical conductivity, while simultaneously enhancing both hydrophilicity and biocompatibility of reduced graphene oxide. In vitro culture of PC12 cells within the cell-laden hydrogel demonstrates its biocompatibility, noncytotoxicity as well as the ability to support long-term cell growth and proliferation. Enhanced neuronal differentiation is also observed, both with and without electrical stimulation. Overall, this 3D conductive, cell-laden hydrogel holds great promise as potential platform for tissue engineering of electroactive tissues.
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Grafito/química , Hidrogeles/química , Imagenología Tridimensional/métodos , Andamios del Tejido , Animales , Bioimpresión , Adhesión Celular , Supervivencia Celular , Conductividad Eléctrica , Electroquímica/métodos , Técnicas In Vitro , Indoles/química , Microscopía Confocal , Microscopía Electrónica de Transmisión , Células PC12 , Polímeros/química , Alcohol Polivinílico/química , Ratas , Espectroscopía Infrarroja por Transformada de Fourier , Ingeniería de Tejidos/métodosRESUMEN
The gharial (Gavialis gangeticus Gmelin) is a fish-eating specialist crocodylian, endemic to south Asia, and critically endangered in its few remaining wild localities. A secondary gharial population resides in riverine-reservoir habitat adjacent to the Nepal border, within the Katerniaghat Wildlife Sanctuary (KWS), and nests along a 10 km riverbank of the Girwa River. A natural channel shift in the mainstream Karnali River (upstream in Nepal) has reduced seasonal flow in the Girwa stretch where gharials nest, coincident with a gradual loss of nest sites, which in turn was related to an overall shift to woody vegetation at these sites. To understand how these changes in riparian vegetation on riverbanks were related to gharial nesting, we sampled vegetation at these sites from 2017 to 2019, and derived an Enhanced Vegetation Index (EVI) from LANDSAT 8 satellite data to quantify riverside vegetation from 1988 through 2019. We found that sampled sites transitioned to woody cover, the number of nesting sites declined, and the number of nests were reduced by > 40%. At these sites, after the channel shift, woody vegetation replaced open sites that predominated prior to the channel shift. Our findings indicate that the lack of open riverbanks and the increase in woody vegetation at potential nesting sites threatens the reproductive success of the KWS gharial population. This population persists today in a regulated river ecosystem, and nests in an altered riparian habitat which appears to be increasingly unsuitable for the continued successful recruitment of breeding adults. This second-ranking, critically endangered remnant population may have incurred an "extinction debt" by living in a reservoir that will lead to its eventual extirpation.
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In recent years, there has been a marked increase in tissue engineering research, particularly in the development of electrospun fiber-based substrates as in vitro cell culture platforms. Many scaffolds fabricated via electrospinning have focused on two-dimensional (2D) mats composed of aligned, random or core-shell nanofibers depending on the application and type of extracellular matrix present inside native tissue. In this study, a novel coaxial electrospinning process with a mixture of polylactic-co-glycolic acid (PLGA) and polyethylene oxide (PEO) for sheaths along with polyvinyl alcohol (PVA) for cores was used to produce hollow microfibers. Subsequent removal of PVA and PEO by dissolution resulted in the formation of hollow fibers containing pores inside the shell. The influence of key electrospinning parameters on fiber diameter and pore size was analyzed and optimized via application of design of experiments (DOE). In addition, a regression model was built to show the mathematical relationships and interdependence between process variables and response. Next, the feasibility of this platform for in vitro cell culture was verified by successfully encapsulating and culturing pheochromocytoma 12 (PC12) cells inside the hollow microfibers, where surface perforations could facilitate nutrient and oxygen diffusion and waste removal. After three days of cultivation, it was found that hollow fibers could provide both guidance and support for adherence and proliferation of PC12 cells. This technique based on coaxial cell electrospinning paves the way for development of controllable, tunable and low-cost platforms facilitating guided and constrained culture of cells inside microfibers, thus highlighting its potential as a tool for designing new types of biohybrid materials.
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Técnicas de Cultivo de Célula , Andamios del Tejido , Animales , Proliferación Celular , Supervivencia Celular , Células PC12 , Polietilenglicoles/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Alcohol Polivinílico/química , Ratas , Ingeniería de Tejidos/métodosRESUMEN
Stress-induced subclinical reactivation of varicella-zoster virus (VZV) has been studied previously. However, subclinical reactivation of VZV induced by the stress of pregnancy has not been investigated. The objective was to study varicella DNA and varicella antibody levels in mothers and their newborn babies. VZV immunoglobulin G (IgG) levels in 350 mother-newborn dyads were studied using indirect enzyme-linked immunosorbent assay testing. A subset of 73 dyads was selected, DNA was isolated from the serum samples, and quantitative polymerase chain reaction (qPCR) was performed. Nearly 15% (14.6%) mothers tested were positive for varicella antibodies (>100 mIU/dL) and 16% were borderline (<100 and >50 mIU/dL). Approximately 16.9% of the babies were positive, and 18% were in borderline. Among those tested for VZV-DNA, 70% of mothers with low VZ-IgG (<100 mIU/dL) and 11.32% of those with high VZ-IgG (>100 mIU/dL) were positive for DNA. Among the newborns, 60% of those with low VZ-IgG and 15% of those with high VZ-IgG were positive for DNA. Mothers who have had VZV infection in the past can transmit VZV DNA to their babies.
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Anticuerpos Antivirales/sangre , ADN Viral/sangre , Herpes Zóster/transmisión , Inmunoglobulina G/sangre , Transmisión Vertical de Enfermedad Infecciosa , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Herpes Zóster/inmunología , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/inmunología , Humanos , Recién Nacido , Infección Latente/virología , Masculino , Madres , Embarazo , Estrés FisiológicoRESUMEN
Increasing evidence indicates superiority of three-dimensional (3D) in vitro cell culture systems over conventional two-dimensional (2D) monolayer cultures in mimicking native in vivo microenvironments. Tissue-engineered 3D culture models combined with stem cell technologies have advanced Alzheimer's disease (AD) pathogenesis studies. However, existing 3D neuronal models of AD overexpress mutant genes or have heterogeneities in composition, biological properties and cell differentiation stages. Here, we encapsulate patient induced pluripotent stem cell (iPSC) derived neural progenitor cells (NPC) in poly(lactic-co-glycolic acid) (PLGA) microtopographic scaffolds fabricated via wet electrospinning to develop a novel 3D culture model of AD. First, we enhanced cellular infiltration and distribution inside the scaffold by optimizing various process parameters such as fiber diameter, pore size, porosity and hydrophilicity. Next, we compared key neural stem cell features including viability, proliferation and differentiation in 3D culture with 2D monolayer controls. The 3D microfibrous substrate reduces cell proliferation and significantly accelerates neuronal differentiation within seven days of culture. Furthermore, 3D culture spontaneously enhanced pathogenic amyloid-beta 42 (Aß42) and phospho-tau levels in differentiated neurons carrying familial AD (FAD) mutations, compared with age-matched healthy controls. Overall, our tunable scaffold-based 3D neuronal culture platform serves as a suitable in vitro model that robustly recapitulates and accelerates the pathogenic characteristics of FAD-iPSC derived neurons.
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Enfermedad de Alzheimer , Células Madre Pluripotentes Inducidas , Células-Madre Neurales , Diferenciación Celular , Humanos , Neuronas , Andamios del TejidoRESUMEN
We report multiscale structured fibers and patterned films based on a semiconducting polymer, poly(3-hexylthiophene) (P3HT), as photoconductive biointerfaces to promote neuronal stimulation upon light irradiation. The micro/nanoscale structures of P3HT used for neuronal interfacing and stimulation include nanofibers with an average diameter of 100 nm, microfibers with an average diameter of about 1 µm, and lithographically patterned stripes with width of 3, 25, and 50 µm, respectively. The photoconductive effect of P3HT upon light irradiation provides electrical stimulation for neuronal differentiation and directed growth. Our results demonstrate that neurons on P3HT nanofibers showed a significantly higher total number of branches, while neurons grown on P3HT microfibers had longer and thinner neurites. Such a combination strategy of topographical and photoconductive stimulation can be applied to further enhance neuronal differentiation and directed growth. These photoconductive polymeric micro/nanostructures demonstrated their great potential for neural engineering and development of novel neural regenerative devices.
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Técnicas de Cultivo de Célula/métodos , Nanofibras/química , Neuronas , Semiconductores , Tiofenos/química , Animales , Técnicas de Cultivo de Célula/instrumentación , Estimulación Eléctrica/instrumentación , Diseño de Equipo , Neuronas/citología , Neuronas/efectos de la radiación , Células PC12 , Procesos Fotoquímicos , Ratas , Ingeniería de Tejidos/instrumentaciónRESUMEN
Rapid surface functionalization of nanomaterials using covalent linkage following "green chemistry" remains challenging, and the quest for developing simple protocols is persisting. We report a nanomechanical microfluidic approach for the coupling of allenamide functionalized organic derivatives on the surface of thiol-modified silica nanoparticles using allenamide-thiol chemistry. The coupling principle involves the use of a microfluidic surface acoustic wave device that generates acoustic streaming-based chaotic fluid micromixing that enables mixing of laterally flowing fluids containing active components. This approach was used to demonstrate the direct surface labeling of thiol-modified silica nanoparticles using a selected group of modified fluorescent tags containing allenamide handles and achieved a total labeling efficiency of 83-90%. This green approach enabled a highly efficient surface functionalization under aqueous conditions, with tunable control over the conjugation process via the applied field. The dye-labeled silica particles were characterized using various analytical techniques and found to be biocompatible with potential in live cell bioimaging. It is envisaged that this bioconjugation strategy will find numerous applications in the field of bioimaging and drug delivery.
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Técnicas Analíticas Microfluídicas/instrumentación , Microscopía Confocal/instrumentación , Nanopartículas/química , Dióxido de Silicio/química , Compuestos de Sulfhidrilo/química , Amidas/química , Línea Celular Tumoral , Diseño de Equipo , Humanos , Técnicas Analíticas Microfluídicas/métodos , Propiedades de SuperficieRESUMEN
Micro/nanofiber-based scaffolds are widely used as a physical graft for axon growth in vitro for nerve tissue engineering. In this study, the fabrication of hollow coaxial microfibers with a 3D structure for directional neuronal cell culture is reported. The coaxial microfibers with poly-ε-caprolactone (PCL) sheath and polyvinyl alcohol (PVA) mixed with PC 12 cells as core are prepared using a coaxial double cylinder based on the liquid-liquid coflowing electrospinning method. By optimizing the electrospinning conditions, uniform microfibers with an average diameter of 54.6 µm are obtained using a PCL concentration of 20% and a tip-to-collector distance of 6 cm with a voltage of 6 kV. After selectively dissolving the PVA core, pheochromocytoma 12 (PC12) cells are successfully cultured inside these fibers. It is experimentally confirmed that such 3D hollow fibers can support and guide PC12 cells to grow, proliferate, and differentiate inside the hollow fibers and form 3D-connected neuronal networks with axons extended along the hollow fibers. This implies that complex nerve connection could be constructed using the low cost and powerful liquid-liquid coflowing electrospinning method, which open the door to culture well-controlled nerve connections as in vitro models for neural tissue regeneration, brain disease models, and so on.
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The draft genome sequence of a novel strain, Pseudomonas sp. MR 02, a pyomelanin-producing bacterium isolated from the Mahananda River at Siliguri, West Bengal, India, is reported here. This strain has a genome size of 5.94 Mb, with an overall G+C content of 62.6%. The draft genome reports 5,799 genes (mean gene length, 923 bp), among which 5,503 are protein-coding genes, including the genes required for the catabolism of tyrosine or phenylalanine for the characteristic production of homogentisic acid (HGA). Excess HGA, on excretion, auto-oxidizes and polymerizes to form pyomelanin.
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Alzheimer's disease (AD) is the most common form of dementia and is characterized by progressive memory loss, impairment of other cognitive functions, and inability to perform activities of daily life. The key to understanding AD aetiology lies in the development of effective disease models, which should ideally recapitulate all aspects pertaining to the disease. A plethora of techniques including in vivo, in vitro, and in silico platforms have been utilized in developing disease models of AD over the years. Each of these approaches has revealed certain essential characteristics of AD; however, none have managed to fully mimic the pathological hallmarks observed in the AD human brain. In this review, we will provide details into the genesis, evolution, and significance of the principal methods currently employed in modelling AD, the advantages and limitations faced in their application, including the headways made by each approach. This review will focus primarily on two-dimensional and three-dimensional in vitro modelling of AD, which during the last few years has made significant breakthroughs in the areas of AD pathology and therapeutic screening. In addition, a glimpse into state-of-the-art neural tissue engineering techniques incorporating biomaterials and microfluidics technologies is provided, which could pave the way for the development of more accurate and comprehensive AD models in the future.