RESUMEN
BACKGROUND OBJECTIVES: More than 1 million people die every year from vector-borne diseases, which constitute more than 17% of all infectious diseases. This study's primary focus is on the detailed evolutionary history and expression analysis of immune genes, one of the key gene families in the immune system of vectors that play a role in the regulation and interaction of parasites in vector bodies, particularly the mosquitoes that transmit malaria and dengue, significant vector borne disease. METHODS: The vector potentiality and participation of TLR genes in vector parasite interaction in the Indian context will be explained by the differential expression study of this potential gene family in Indian populations of vector species. RESULTS: This knowledge is supportive undoubtedly for creating new pharmacological targets and inhibitors that can create insect-based transmission stopping techniques for many vector-borne diseases. INTERPRETATION CONCLUSION: However, the genetic diversity was found to be comparatively lower in the Toll1A gene than in the NOS immune gene in the malaria vector An. minimus population samples which supports the hypothesis of positive selection in recent evolutionary time scale in malaria vectors. This is one of the novel strategies to identify transmission regulating genetic traits that are controlling the vector-parasite interaction and co-evolution in vector borne disease.
RESUMEN
Acquired hemophilia A is a rare condition characterized by the development of autoantibodies against coagulation factor VIII. It often initially presents as serious bleeding in the absence of risk factors and carries high morbidity and mortality if not diagnosed early. Due to its rare nature, data is limited, and guidelines are primarily based on expert opinion. Here we present a case of an elderly patient with severe gastrointestinal bleeding found to have activated partial thromboplastin times, plasma mixing studies, and coagulation factor activity levels consistent with acquired hemophilia A. We hope to bring awareness of this rare disease and promote its consideration in the differential of unexpected bleeding to improve safety outcomes.
RESUMEN
Fast-scan cyclic voltammetry (FSCV) is an electrochemical sensing technique that can be used for neurochemical sensing with high spatiotemporal resolution. Carbon fiber microelectrodes (CFMEs) are traditionally used as FSCV sensors. However, CFMEs are prone to electrochemical fouling caused by oxidative byproducts of repeated serotonin (5-HT) exposure, which makes them less suitable as chronic 5-HT sensors. Our team is developing a boron-doped diamond microelectrode (BDDME) that has previously been shown to be relatively resistant to fouling caused by protein adsorption (biofouling). We sought to determine if this BDDME exhibits resistance to electrochemical fouling, which we explored on electrodes fabricated with either femtosecond laser cutting or physical cleaving. We recorded the oxidation current response after 25 repeated injections of 5-HT in a flow-injection cell and compared the current drop from the first with the last injection. The 5-HT responses were compared with dopamine (DA), a neurochemical that is known to produce minimal fouling oxidative byproducts and has a stable repeated response. Physical cleaving of the BDDME yielded a reduction in fouling due to 5-HT compared with the CFME and the femtosecond laser cut BDDME. However, the femtosecond laser cut BDDME exhibited a large increase in sensitivity over the cleaved BDDME. An extended stability analysis was conducted for all device types following 5-HT fouling tests. This analysis demonstrated an improvement in the long-term stability of boron-doped diamond over CFMEs, as well as a diminishing sensitivity of the laser-cut BDDME over time. This work reports the electrochemical fouling performance of the BDDME when it is repeatedly exposed to DA or 5-HT, which informs the development of a chronic, diamond-based electrochemical sensor for long-term neurotransmitter measurements in vivo.
Asunto(s)
Boro , Diamante , Técnicas Electroquímicas , Microelectrodos , Serotonina , Serotonina/análisis , Boro/química , Diamante/química , Técnicas Biosensibles , Dopamina/análisis , Fibra de Carbono , Oxidación-ReducciónRESUMEN
Background and Aims: A Key Performance Indicator (KPI) is a critical metric measuring organizational success or specific activities, reflecting the periodic achievement of operational goals aligned with strategic objectives. Material and Methods: A retrospective cross-sectional study of key quality performance indicators, (CQI-NABH) concerning anesthesia and surgical services was conducted at a tertiary care hospital after taking institutional ethical clearance (AIIMS/IEC/21/150). It was as per COP 13, COP 14, and COP 15 standards of NABH 4th edition published in 2015. The study was conducted at the department of anesthesiology at a tertiary care hospital, and data were retrospectively analyzed from 01 October 2019, till November 2020. All patients undergoing elective or emergency surgical procedures under monitored anesthesia care and regional or general anesthesia during the study period were considered.The primary objective was to analyze Continuous Quality Improvement (CQI) in perioperative services, with secondary goals including gap identification, suggesting corrective actions, and examining quality indicators during the COVID-19 pandemic in 2020. Results: Out of 8574 patients operated during the study, 6705 were in the four months before the pandemic, and 1869 were operated during the COVID-19 scenario. In the pre-COVID era, many of the cases were performed on an elective basis (71.23%), and emergencies constituted 16.9% of the total number of cases. In the COVID era, most of the cases were emergencies (45.4%) and semi-emergencies (40.25%), and elective cases were only 14.05% of the total cases performed. The percentage of modification of anaesthesia plans ranged from 0-3.34%. Adverse anaesthesia events were observed in 0-2.1%, primarily related to cardiovascular, respiratory, and airway issues. No anaesthesia-related mortality was reported. Prophylactic antibiotic administration within one hour of surgery ranged from 88-100%. Conclusions: Monitoring and evaluating healthcare performance, specifically through KPIs, is vital for optimizing care and resource utilization. These indicators provide an overview of hospital service efficiency, aiding in key areas such as patient treatment, satisfaction, healthcare quality improvement, cost reduction, and optimal resource utilization. Addressing identified issues ensures effective and sustainable quality improvement in anaesthesia services, emphasizing ongoing monitoring as a foundation for hospital quality assurance.
RESUMEN
Implantable neurotechnology enables monitoring and stimulating of the brain signals responsible for performing cognitive, motor, and sensory tasks. Electrode arrays implanted in the brain are increasingly used in the clinic to treat a variety of sources of neurological diseases and injuries. However, the implantation of a foreign body typically initiates a tissue response characterized by physical disruption of vasculature and the neuropil as well as the initiation of inflammation and the induction of reactive glial states. Likewise, electrical stimulation can induce damage to the surrounding tissue depending on the intensity and waveform parameters of the applied stimulus. These phenomena, in turn, are likely influenced by the surface chemistry and characteristics of the materials employed, but further information is needed to effectively link the biological responses observed to specific aspects of device design. In order to inform improved design of implantable neurotechnology, we are investigating the basic science principles governing device-tissue integration. We are employing multiple techniques to characterize the structural, functional, and genetic changes that occur in the cells surrounding implanted electrodes. First, we have developed a new "device-in-slice" technique to capture chronically implanted electrodes within thick slices of live rat brain tissue for interrogation with single-cell electrophysiology and two-photon imaging techniques. Our data revealed several new observations of tissue remodeling surrounding devices: (a) there was significant disruption of dendritic arbors in neurons near implants, where losses were driven asymmetrically on the implant-facing side. (b) There was a significant loss of dendritic spine densities in neurons near implants, with a shift toward more immature (nonfunctional) morphologies. (c) There was a reduction in excitatory neurotransmission surrounding implants, as evidenced by a reduction in the frequency of excitatory postsynaptic currents (EPSCs). Lastly, (d) there were changes in the electrophysiological underpinnings of neuronal spiking regularity. In parallel, we initiated new studies to explore changes in gene expression surrounding devices through spatial transcriptomics, which we applied to both recording and stimulating arrays. We found that (a) device implantation is associated with the induction of hundreds of genes associated with neuroinflammation, glial reactivity, oligodendrocyte function, and cellular metabolism and (b) electrical stimulation induces gene expression associated with damage or plasticity in a manner dependent upon the intensity of the applied stimulus. We are currently developing computational analysis tools to distill biomarkers of device-tissue interactions from large transcriptomics data sets. These results improve the current understanding of the biological response to electrodes implanted in the brain while producing new biomarkers for benchmarking the effects of novel electrode designs on responses. As the next generation of neurotechnology is developed, it will be increasingly important to understand the influence of novel materials, surface chemistries, and implant architectures on device performance as well as the relationship with the induction of specific cellular signaling pathways.
Asunto(s)
Encéfalo , Electrodos Implantados , Animales , Encéfalo/metabolismo , RatasRESUMEN
ABSTRACT: Postoperative visual loss (POVL) is an infrequent yet consequential complication that can follow cardiac surgical interventions. This systematic review aims to provide a comprehensive analysis of the incidence of POVL after cardiac surgery and to delineate the associated risk factors. A comprehensive search was conducted in major medical databases for relevant studies published up to September 2022. Eligible studies reporting on the incidence of POVL and identifying risk factors in patients undergoing cardiac surgery were included. Data extraction was performed independently by two reviewers. The pooled incidence rates and the identified risk factors were synthesized qualitatively. POVL after cardiac surgery has an overall incidence of 0.015%, that is, 15 cases per 100,000 cardiac surgical procedures. Risk factors for POVL include patient characteristics (advanced age, diabetes, hypertension, and preexisting ocular conditions), procedural factors (prolonged surgery duration, cardiopulmonary bypass time, and aortic cross-clamping), anesthetic considerations (hypotension, blood pressure fluctuations, and specific techniques), and postoperative complications (stroke, hypotension, and systemic hypoperfusion). Ischemic optic neuropathy (ION) is an uncommon complication, associated with factors like prolonged cardiopulmonary bypass, low hematocrit levels, excessive body weight gain, specific medications, hypothermia, anemia, raised intraocular pressure, and micro-embolization. Diabetic patients with severe postoperative anemia are at increased risk for anterior ischemic optic neuropathy (AION). Posterior ischemic optic neuropathy (PION) can occur with factors like hypertension, postoperative edema, prolonged mechanical ventilation, micro-embolization, inflammation, hemodilution, and hypothermia.While the overall incidence of POVL postcardiac surgery remains modest, its potential impact is substantial, necessitating meticulous consideration of modifiable risk factors. Notably, prolonged surgical duration, intraoperative hypotension, anemia, and reduced hematocrit levels remain salient contributors. Vigilance is indispensable to promptly detect this infrequent yet visually debilitating phenomenon in the context of postcardiac surgical care.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Complicaciones Posoperatorias , Humanos , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Incidencia , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Trastornos de la Visión/etiología , Trastornos de la Visión/epidemiología , Ceguera/etiología , Ceguera/epidemiologíaRESUMEN
This study employed subtractive proteomics and immunoinformatics to analyze the Wuchereria bancrofti proteome and identify potential therapeutic targets, with a focus on designing a vaccine against the parasite species. A comprehensive bioinformatics analysis of the parasite's proteome identified 51 probable therapeutic targets, among which "Kunitz/bovine pancreatic trypsin inhibitor domain-containing protein" was identified as the most promising vaccine candidate. The candidate protein was used to design a multi-epitope vaccine, incorporating B-cell and T-cell epitopes identified through various tools. The vaccine construct underwent extensive analysis of its antigenic, physical, and chemical features, including the determination of secondary and tertiary structures. Docking and molecular dynamics simulations were performed with HLA alleles, Toll-like receptor 4 (TLR4), and TLR3 to assess its potential to elicit the human immune response. Immune simulation analysis confirmed the predicted vaccine's strong binding affinity with immunoglobulins, indicating its potential efficacy in generating an immune response. However, experimental validation and testing of this multi-epitope vaccine construct would be needed to assess its potential against W. bancrofti and even for a broader range of lymphatic filarial infections given the similarities between W. bancrofti and Brugia.
Asunto(s)
Proteoma , Wuchereria bancrofti , Humanos , Animales , Bovinos , Proteómica , Epítopos de Linfocito T , Aprotinina , Simulación de Dinámica MolecularRESUMEN
Juvenile ossifying fibroma (JOF) is a rare type of tumor originating from the bones of the face or cranium. It usually arises in the maxilla and rarely in the mandible. The complications related to the tumor are because of local expansion and resultant effect on the nearby organs. We present the case of an eight-year-old girl with a history of headache and chronic epistaxis for the past six months who presented acutely to the hospital due to swelling, redness, and pain in both eyes, with continuous epistaxis. After investigations, she was found to have a nasal tumor that was confirmed to be JOF of the nasal bone on histopathology. Surgical management was done and the tumor was resected.
RESUMEN
BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms of the gastrointestinal tract (GIT) that represent approximately 1 to 2 percent of primary gastrointestinal (GI) cancers. Owing to their rarity, very little is known about their overall epidemiology, and the prognostic factors of their pathology. The current study aimed to evaluate the independent determinants of mortality in patients diagnosed with GISTs over the past decade. METHODS: Our study comprised 2374 patients diagnosed with GISTs from 2000 to 2017 from the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed the baseline characteristics, and overall mortality (OM), as well as the cancer-specific mortality (CSM) of GISTs. Variables with a p value < 0.01 in the univariate Cox regression were incorporated into the multivariate Cox model, to determine the independent prognostic factors. RESULTS: Multivariate Cox proportional hazard regression analyses of factors affecting the all-cause mortality and GIST-related mortality among US patients between 2010 and 2017 revealed a higher overall mortality in non-Hispanic Black patients (HR = 1.516, 95% CI 1.172-1.961, p = 0.002), patients aged 80+ (HR = 9.783, 95% CI 4.185-22.868, p = 0), followed by those aged 60-79 (HR = 3.408, 95% CI 1.488-7.807, p = 0.004); male patients (HR = 1.795, 95% CI 1.461-2.206, p < 0.001); patients with advanced disease with distant metastasis (HR = 3.865, 95% CI 2.977-5.019, p < 0.001), followed by cases with regional involvement via both direct extension and lymph node involvement (HR = 3.853, 95% CI 1.551-9.57, p = 0.004); and widowed patients (HR = 1.975, 95% CI 1.494-2.61, p < 0.001), followed by single patients (HR = 1.53, 95% CI 1.154-2.028, p = 0.003). The highest CSM was observed in the same groups, except widowed patients and patients aged 60-79. The highest CSM was also observed among patients that underwent chemotherapy (HR = 1.687, 95% CI 1.19-2.392, p = 0.003). CONCLUSION: In this updated study on the outcomes of patients with GISTs, we found that non-Hispanic Black patients, male patients, and patients older than 60 years have a higher mortality with GISTs. Furthermore, patients who have received chemotherapy have a higher GIST-specific mortality, and married patients have a lower mortality. However, we do not know to what extent these independent prognostic factors interact with each other to influence mortality. This study paves the way for future studies addressing these interactions. The results of this study may help treating clinicians to identify patient populations associated with a dismal prognosis, as those may require closer follow-up and more intensive therapy; furthermore, with married patients having a better survival rate, we hope to encourage clinicians to involve family members of the affected patients early in the disease course, as the social support might impact the prognosis.
Asunto(s)
Tumores del Estroma Gastrointestinal , Humanos , Masculino , Bases de Datos Factuales , Progresión de la Enfermedad , Tumores del Estroma Gastrointestinal/terapia , Negro o Afroamericano , Evaluación de Resultado en la Atención de Salud , Anciano , Anciano de 80 o más Años , Persona de Mediana EdadRESUMEN
RNA-binding proteins (RBPs) are the proteins that bind RNAs and regulate their functioning. RBPs in mosquitoes are gaining attention due to their ability to bind flaviviruses and regulate their replication and transmission. Despite their relevance, RBPs in mosquitoes are not explored much. In this study, we screened the whole genome of Aedes aegypti, the primary vector of several pathogenic viruses, and identified the proteins containing RNA recognition motif (RRM), the most abundant protein domain in eukaryotes. Using several in silico strategies, a total of 135 RRM-containing RBPs were identified in Ae. aegypti. The proteins were characterized based on their available annotations and the sequence similarity with Drosophila melanogaster. Ae. aegypti RRM-containing RBPs included serine/arginine-rich (SR) proteins, polyadenylate-binding proteins (PABP), heteronuclear ribonucleoproteins (hnRNP), small nuclear ribonucleoproteins (snRNP), splicing factors, eukaryotic initiation factors, transformers, and nucleolysins. Phylogenetic analysis revealed that the proteins and the domain organization are conserved among Ae. aegypti, Bombyx mori, and Drosophila melanogaster. However, the gene length and the intron-exon organization varied across the insect species. Expression analysis of the genes encoding RBPs using publicly available RNA sequencing data for different developmental time points of the mosquito life cycle starting from the ovary and eggs up to the adults revealed stage-specific expression with several genes preferentially expressed in early embryonic stages and blood-fed female ovaries. This is the first database for the Ae. aegypti RBPs that can serve as the reference base for future investigations. Stage-specific genes can be further explored to determine their role in mosquito growth and development with a focus on developing novel mosquito control strategies.
Asunto(s)
Aedes , Animales , Femenino , Aedes/fisiología , Proteínas con Motivos de Reconocimiento de ARN/genética , Drosophila melanogaster/genética , Filogenia , Motivo de Reconocimiento de ARN , Mosquitos Vectores , Proteínas de Unión al ARN/genética , ARNRESUMEN
Coronavirus disease-2019 (COVID-19) is an extremely contagious illness caused by the SARS-CoV-2 virus and has been declared a pandemic by the World Health Organization (WHO). There are currently no particular treatments, however, nebulized heparin has been offered as a viable therapy. The purpose of this systematic review is to assess the efficacy of nebulized heparin in COVID-19 patients with respiratory symptoms. Methods: Relevant studies were identified through a systematic search of the PubMed, Medline, Embase, Cochrane Library and Web of Science, and Scopus databases. The search terms included "nebulized heparin," "COVID-19," and "SARS-CoV-2." Studies that evaluated the use of nebulized heparin in COVID-19 patients with respiratory symptoms were included. The rest of the studies along with those that were not published in English were excluded. The systematic review was registered under PROSPERO-CRD42023413927. Observations: Five studies have been included in this systematic review. Case reports, case series, observational studies, and randomized controlled trial (RCT) comprised the studies. The patient sample sizes ranged from 2 to 98. The studies assessed the efficacy of nebulized heparin in COVID-19 patients with variable disease severity. The evaluated outcomes included mortality, hospital stay duration, oxygen requirements, and laboratory parameters. Conclusion: Based on the clinical studies included in this systematic review, nebulized heparin may be useful in the management of COVID-19. Oxygen saturation was greater, inflammatory indicators were lower, and hospital stays were shorter in these patients. However, the studies had limitations, including inconsistent sample sizes, varying dosages of nebulized heparin, and no control groups. Nebulized heparin in patients with COVID-19 needs to be studied further to determine its safety and effectiveness. How to cite this article: Gupta B, Ahluwalia P, Gupta N, Gupta A. Role of Nebulized Heparin in Clinical Outcome of COVID-19 Patients with Respiratory Symptoms: A Systematic Review. Indian J Crit Care Med 2023;27(8):572-579.
RESUMEN
Rickettsia is an important pathogenic entity among tick-borne diseases (TBD), which are considered serious emerging public health problems globally. In India, though the widespread distribution of ticks and TBD has been documented, its real burden remains underreported. In a preliminary attempt, rickettsial surveillance was carried out in ticks collected from Sirumalai, Eastern Ghats in Tamil Nadu, India by using pathogen genome-based phylogenetic inferences generated through multi-locus sequence typing (MLST), targeting the genes 16s rRNA, OmpA, OmpB, and gltA by nested PCR. The laboratory evidence confirms the circulation of Rickettsia in Haemaphysalis intermedia species collected from this area. Analysis of the four gene sequences detected demonstrates their closest identity to the spotted fever group (SFG) available in the GenBank database. Further, multiple sequence alignment with other sequences derived from the GenBank database showed close relatedness to Rickettsia conorii subsp. raoultii (16s rDNA-99.32%, OmpA-93.38%, OmpB-97.39%, and gltA-98.57%) and Rickettsia felis (16s rDNA 99.54%, OmpA-100%, OmpB-100% and gltA-99.41%). With this genomic evidence, the circulation of rickettsial pathogens in the pools of H. intermedia ticks infesting livestock in the Sirumalai foothill area has been demonstrated and to complement the microscopic identification of the tick species, DNA barcodes were generated for H. intermedia using the mitochondrial cytochrome c oxidase subunit I gene (COI). Nevertheless, R. raoultii and R. felis were found to be the aetiological agents of tick-borne lymphadenopathy and flea-borne spotted fever in human cases, respectively, further study on the determination of their diversity, distribution, clinical relevance, and potential risk to the local community in these areas is highly warranted.
RESUMEN
The present study explicitly evaluated the genetic structure of Aedes aegypti Linn, the vector of dengue, chikungunya, and Zika viruses, across different geo-climatic zones of India and also elucidated the impact of ecological and topographic factors. After data quality checks and removal of samples with excess null alleles, the final analysis was performed on 589 individual samples using 10 microsatellite markers. Overall findings of this study suggested that, Ae. aegypti populations are highly diverse with moderate genetic differentiation between them. Around half of the populations (13 out of 22) formed two genetic clusters roughly associated with geographical regions. The remaining nine populations shared genetic ancestries with either one or both of the clusters. A significant relationship between genetic and geographic distance was observed, indicating isolation by distance. However, spatial autocorrelation analysis predicted the signs of long-distance admixture. Post-hoc environmental association analysis showed that 52.7% of genetic variations were explained by a combination of climatic and topographic factors, with latitude and temperature being the best predictors. This study indicated that though overall genetic differentiation among Ae. aegypti populations across India is moderate (Fst = 0.099), the differences between the populations are developing due to the factors associated with geographic locations. This study improves the understanding of the Ae. aegypti population structure in India that may assist in predicting mosquito movements across the geo-climatic zones, enabling effective control strategies and assessing the risk of disease transmission.