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1.
Lancet Reg Health Am ; 32: 100706, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38495312

RESUMO

Tick-borne diseases (TBD) remain prevalent worldwide, and risk assessment of tick habitat suitability is crucial to prevent or reduce their burden. This scoping review provides a comprehensive survey of models and data used to predict I. scapularis distribution and abundance in North America. We identified 4661 relevant primary research articles published in English between January 1st, 2012, and July 18th, 2022, and selected 41 articles following full-text review. Models used data-driven and mechanistic modelling frameworks informed by diverse tick, hydroclimatic, and ecological variables. Predictions captured tick abundance (n = 14, 34.1%), distribution (n = 22, 53.6%) and both (n = 5, 12.1%). All studies used tick data, and many incorporated both hydroclimatic and ecological variables. Minimal host- and human-specific data were utilized. Biases related to data collection, protocols, and tick data quality affect completeness and representativeness of prediction models. Further research and collaboration are needed to improve prediction accuracy and develop effective strategies to reduce TBD.

2.
Cell Rep ; 42(11): 113395, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37967557

RESUMO

Traumatic brain injury (TBI) is a leading cause of chronic brain impairment and results in a robust, but poorly understood, neuroinflammatory response that contributes to the long-term pathology. We used single-nuclei RNA sequencing (snRNA-seq) to study transcriptomic changes in different cell populations in human brain tissue obtained acutely after severe, life-threatening TBI. This revealed a unique transcriptional response in oligodendrocyte precursors and mature oligodendrocytes, including the activation of a robust innate immune response, indicating an important role for oligodendroglia in the initiation of neuroinflammation. The activation of an innate immune response correlated with transcriptional upregulation of endogenous retroviruses in oligodendroglia. This observation was causally linked in vitro using human glial progenitors, implicating these ancient viral sequences in human neuroinflammation. In summary, this work provides insight into the initiating events of the neuroinflammatory response in TBI, which has therapeutic implications.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Retrovirus Endógenos , Humanos , Animais , Camundongos , Retrovirus Endógenos/genética , Doenças Neuroinflamatórias , Transcriptoma/genética , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas/patologia , Oligodendroglia/patologia , Inflamação/genética , Inflamação/patologia , Camundongos Endogâmicos C57BL
3.
Sci Adv ; 9(44): eadh9543, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37910626

RESUMO

The genetic mechanisms underlying the expansion in size and complexity of the human brain remain poorly understood. Long interspersed nuclear element-1 (L1) retrotransposons are a source of divergent genetic information in hominoid genomes, but their importance in physiological functions and their contribution to human brain evolution are largely unknown. Using multiomics profiling, we here demonstrate that L1 promoters are dynamically active in the developing and the adult human brain. L1s generate hundreds of developmentally regulated and cell type-specific transcripts, many that are co-opted as chimeric transcripts or regulatory RNAs. One L1-derived long noncoding RNA, LINC01876, is a human-specific transcript expressed exclusively during brain development. CRISPR interference silencing of LINC01876 results in reduced size of cerebral organoids and premature differentiation of neural progenitors, implicating L1s in human-specific developmental processes. In summary, our results demonstrate that L1-derived transcripts provide a previously undescribed layer of primate- and human-specific transcriptome complexity that contributes to the functional diversification of the human brain.


Assuntos
Retroelementos , Transcriptoma , Animais , Humanos , Retroelementos/genética , Elementos Nucleotídeos Longos e Dispersos/genética , Neurônios , Primatas/genética
4.
J Natl Med Assoc ; 115(6): 556-565, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37845145

RESUMO

BACKGROUND: Sickle Cell Disease (SCD) is the most prevalent hemoglobinopathy, impacting around 5% of the global population. The Indian tribal population, which has been a key focus of the Indian SCD program, can experience health-related stigma due to the multidimensional impact of the disease. This preliminary qualitative inquiry delves into the lived experiences of individuals and synthesizes domains to identify the sources of stigma. METHODOLOGY: The study's framework for developing the stigma tool was rooted in Bronfenbrenner's Ecology of Human Development. The study was implemented in five tribal-dominated districts of India and involved in-depth interviews with sickle cell disease (SCD) patients and their caregivers to explore their stigmatizing experiences. RESULTS: The analysis revealed four overarching themes and several subthemes explaining the type of stigma, its source, and factors contributing to stigmatization. First, the study focused on elements associated with perceived stigma, such as disclosure, self-isolation/refusal to participate, and self-judgment. The second theme pertained to the internalization of stigma. The third theme addressed experienced stigma concerning the disease's impact on day-to-day events, and the fourth theme explored the support system patients needed. The framework highlighted the varying degrees of stigmatizing components within different aspects of patients' ecology. CONCLUSION: Our study highlights the importance of addressing stigma at various levels. Policies, programs, and healthcare interventions must target stigma across these levels. Culturally adaptive tools for identifying stigma, implementing appropriate interventions, and improving healthcare participation are essential for enhancing the quality of life and reducing the disease burden.


Assuntos
Anemia Falciforme , Qualidade de Vida , Humanos , Estigma Social , Anemia Falciforme/epidemiologia , Anemia Falciforme/complicações , Pesquisa Qualitativa , Efeitos Psicossociais da Doença
5.
J Biomol Struct Dyn ; : 1-15, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37712855

RESUMO

Here, we describe hitherto unknown shape-function of S/O-HexNActransferase SvGT (ORF AQF52_3101) instrumental in glycosylation of bacteriocin SvC (ORF AQF52_3099) in Streptomyces venezuelae ATCC 15439. Data from gel filtration, mass spectrometry, analytical ultracentrifugation, and Small Angle X-ray Scattering (SAXS), experiments confirmed elongated dimeric shape in solution for SvGT protein. Enzyme assays confirmed the dependence of SvGT on the availability of Mg2+ ions to be functionally activated. SAXS data analysis provided that apo and Mg2+-activated protein adopt a shape characterized by a radius of gyration and maximum linear dimension of 5.2 and 17.0 nm, and 5.3 and 17.8 nm, respectively. Alphafold2 server was used to model the monomeric chain of this protein which was docked on self to obtain different poses of the dimeric entity. Experimental SAXS data was used to select and refine the structure of SvGT dimer. Results showed that Mg2+ ions induce reorientation of the GT domain of one chain leading to a dimer with C2 symmetry, and the C-terminal portion entangles with each other in all states. Mutation-rendered alteration in activity profiles confirmed the role of conserved residues around catalytic motif. Global structure analysis puts forth the need to understand the role of constitutionally diverse C-terminal portion in regulating substrate selectivity.Communicated by Ramaswamy H. Sarma.

6.
Biogerontology ; 24(5): 609-662, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37516673

RESUMO

Aging accompanied by several age-related complications, is a multifaceted inevitable biological progression involving various genetic, environmental, and lifestyle factors. The major factor in this process is oxidative stress, caused by an abundance of reactive oxygen species (ROS) generated in the mitochondria and endoplasmic reticulum (ER). ROS and RNS pose a threat by disrupting signaling mechanisms and causing oxidative damage to cellular components. This oxidative stress affects both the ER and mitochondria, causing proteopathies (abnormal protein aggregation), initiation of unfolded protein response, mitochondrial dysfunction, abnormal cellular senescence, ultimately leading to inflammaging (chronic inflammation associated with aging) and, in rare cases, metastasis. RONS during oxidative stress dysregulate multiple metabolic pathways like NF-κB, MAPK, Nrf-2/Keap-1/ARE and PI3K/Akt which may lead to inappropriate cell death through apoptosis and necrosis. Inflammaging contributes to the development of inflammatory and degenerative diseases such as neurodegenerative diseases, diabetes, cardiovascular disease, chronic kidney disease, and retinopathy. The body's antioxidant systems, sirtuins, autophagy, apoptosis, and biogenesis play a role in maintaining homeostasis, but they have limitations and cannot achieve an ideal state of balance. Certain interventions, such as calorie restriction, intermittent fasting, dietary habits, and regular exercise, have shown beneficial effects in counteracting the aging process. In addition, interventions like senotherapy (targeting senescent cells) and sirtuin-activating compounds (STACs) enhance autophagy and apoptosis for efficient removal of damaged oxidative products and organelles. Further, STACs enhance biogenesis for the regeneration of required organelles to maintain homeostasis. This review article explores the various aspects of oxidative damage, the associated complications, and potential strategies to mitigate these effects.


Assuntos
Estresse Oxidativo , Fosfatidilinositol 3-Quinases , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/fisiologia , Antioxidantes/metabolismo , Autofagia
7.
Cureus ; 15(5): e39390, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37378110

RESUMO

OBJECTIVE: We aimed to report the pattern of road traffic injuries (RTIs) and pre-hospitalization factors of road traffic injuries among the accident victims reported at an urban and a rural healthcare facility in the Jaipur district, Rajasthan. METHODS: This cross-sectional study was conducted in a tertiary-level, urban public healthcare facility in Jaipur city and a secondary-level, rural private facility in nearby Chomu town. The study participants were all those who encountered road traffic injury and visited any of these healthcare facilities to seek care. The study tool included information on demographics, type of road user, vehicles, accidents, roads, environment, and other pre-hospitalization factors. Data collectors were nurses trained to collect data using the tablet-based application. Data were analyzed using proportions/percentages. Bivariate analysis was done to assess the significance of differences between categories of factors and between rural and urban facilities. RESULTS: Among 4,642 cases, 93.8% were enrolled in the urban facility, and the remaining were enrolled in the rural facility. Predominantly, males (83.9%) and young adults 18-34 years (58.9%) were reported in both study facilities. Among the accident victims reported at the urban facility, major groups were educated up to the primary level (25.1%) or graduate level (21.9%). About 60% of them were drivers. Most of these injuries occurred on urban roads (50.2%) or two-lane roads (42%). About three-fourths of the injured were using two-wheeler geared vehicles, and 46.7% were overtaking or turning the vehicle when the accident happened. The majority of cases (61.6%) did not require hospitalization. Among the rural facility participants, 27.2% were graduates, and 24.7% were below primary education. Most of these injuries happened on the national highway (35.8%) or rural roads (33.3%). Most of them used two-wheeler geared (80.1%) at the time of the accident. Most were injured while doing normal straight driving (80.5%). Most participants (80.1%) in the rural facility did not follow the traffic rules, and 43.9% required hospitalization. CONCLUSION: Young males were the most affected age group by road traffic injuries. Differential patterns of road traffic injuries and pre-hospital factors were observed in urban and rural areas.

8.
Int J Health Plann Manage ; 38(5): 1483-1494, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37340519

RESUMO

In India, sickle cell disease (SCD) predominantly occurs in indigenous (tribal) people, who are about 104 million. However, screening and diagnosis seldom happen. This situation necessitates developing a comprehensive SCD care model, including a registry. This paper describes the development and implementation of the Indian SCD registry (ISCDR) in six tribal-dominated districts of India. The ISCDR was created in two components-(i) an Android-based mobile/tablet application, (ii) a dashboard/admin panel for patients' data management and retrieval. Data capture involves two electronic case report forms (CRF), that is, the primary form (CRF-1) and the repeat visit form (CRF-2). CRF-1 is completed as soon as the patient is found positive and captures the patient's information, including medical history, diagnosis, symptoms, precipitating factors, hospitalisation history and treatment received. Issues related to quality, security and data-sharing were addressed. After the screening system was functional, ISCDR was initiated. In 12 months, data of 324 SCD patients and 1771 carriers were entered. The study demonstrates the feasibility of establishing an SCD registry in India. It collects systematic longitudinal data on SCD patients, which are essential for programme planning and management. Further, it is feasible to scale up and integrate with other health management databases.


Assuntos
Anemia Falciforme , Humanos , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Hospitalização , Sistema de Registros , Índia/epidemiologia
9.
J Med Screen ; 30(1): 28-35, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36036388

RESUMO

OBJECTIVE: To describe the development and implementation of a population-based screening programme for sickle cell disease (SCD) implemented in 12 SCD-endemic and tribal-dominated primary/community health centres (PHCs/CHCs) across six districts of India. SETTING: India reports a huge burden of SCD, especially among indigenous (tribal) communities. However, there is no state-led SCD programme in many places, and systematic screening is absent. This situation necessitates developing a model of population screening. METHODS: This programme was meant to screen all people and was carried out in three tiers. The first tier was a symptomatic survey carried out by community health workers. Regular health workers then screened those referred by sickle cell solubility test at sub-health centres as the second tier. The third tier was confirmation by haemoglobin electrophoresis at PHCs/CHCs. Communities were mobilised and prepared to accept the screening. Capacity building of health facilities was ensured through training and supply of equipment and material. RESULTS: Initial observation based on six months' data revealed that out of the 110,754 tribal population of 12 PHCs/CHCs, 8418 (7.6%) were identified in the symptomatic survey. Subsequently, 9416 people, including the above 8418, underwent the solubility test, and 2607 (27.7%) were found to be positive. Of these, 1978 (78.9%) underwent electrophoresis. About 64.2% were found to be positive for sickle haemoglobin (233 (18.4%) SCD and 1036 (81.6%) SCD trait). CONCLUSIONS: The study demonstrates the feasibility of establishing a population-based screening programme in the primary health care system. It is easy to implement in tribal habitations as part of the proposed national SCD/haemoglobinopathies programme.


Assuntos
Anemia Falciforme , Detecção Precoce de Câncer , Humanos , Estudos de Viabilidade , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Atenção à Saúde , Índia/epidemiologia
10.
Hemoglobin ; 47(6): 227-236, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38189147

RESUMO

Sickle cell disease (SCD) affects 5% of the global population, with over 300,000 infants born yearly. In India, 73% of those with the sickle hemoglobin gene belong to indigenous tribes in remote regions lacking proper healthcare. Despite the prevalence of SCD, India lacked state-led public health programs until recently, leaving a gap in screening and comprehensive care. Hence, the Indian Council of Medical Research conducted implementation research to address this gap. This paper discusses the development and impact of the program, including screening and treatment coverage for SCD in tribal areas. With a quasi-experimental design, this study was conducted in six tribal-dominated districts in three phases - formative, intervention, and evaluation. The intervention included advocacy, partnership building, building the health system's capacity and community mobilization, and enabling the health systems to screen and manage SCD patients. The capacity building included improving healthcare workers' skills through training and infrastructure development of primary healthcare (PHC) facilities. The impact of the intervention is visible in terms of people's participation (54%, 76% and 93% of the participants participated in some intervention activities, underwent symptomatic screening and demanded the continuity of the program, respectively), and improvement in SCD-related knowledge of the community and health workers (with more than 50% of net change in many of the knowledge-related outcomes). By developing screening and treatment models, this intervention model demonstrated the feasibility of SCD care at the PHC level in remote rural areas. This accessible approach allows the tribal population in India to routinely seek SCD care at their local PHCs, offering great convenience. Nevertheless, additional research employing rigorous methodology is required to fine-tune the model. National SCD program may adopt this model, specifically for community-level screening and management of SCD in remote and rural areas.


Assuntos
Anemia Falciforme , Lactente , Humanos , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Índia/epidemiologia
11.
PLoS Comput Biol ; 18(12): e1010755, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36508463

RESUMO

Close-kin mark-recapture (CKMR) methods have recently been used to infer demographic parameters such as census population size and survival for fish of interest to fisheries and conservation. These methods have advantages over traditional mark-recapture methods as the mark is genetic, removing the need for physical marking and recapturing that may interfere with parameter estimation. For mosquitoes, the spatial distribution of close-kin pairs has been used to estimate mean dispersal distance, of relevance to vector-borne disease transmission and novel biocontrol strategies. Here, we extend CKMR methods to the life history of mosquitoes and comparable insects. We derive kinship probabilities for mother-offspring, father-offspring, full-sibling and half-sibling pairs, where an individual in each pair may be a larva, pupa or adult. A pseudo-likelihood approach is used to combine the marginal probabilities of all kinship pairs. To test the effectiveness of this approach at estimating mosquito demographic parameters, we develop an individual-based model of mosquito life history incorporating egg, larva, pupa and adult life stages. The simulation labels each individual with a unique identification number, enabling close-kin relationships to be inferred for sampled individuals. Using the dengue vector Aedes aegypti as a case study, we find the CKMR approach provides unbiased estimates of adult census population size, adult and larval mortality rates, and larval life stage duration for logistically feasible sampling schemes. Considering a simulated population of 3,000 adult mosquitoes, estimation of adult parameters is accurate when ca. 40 adult females are sampled biweekly over a three month period. Estimation of larval parameters is accurate when adult sampling is supplemented with ca. 120 larvae sampled biweekly over the same period. The methods are also effective at detecting intervention-induced increases in adult mortality and decreases in population size. As the cost of genome sequencing declines, CKMR holds great promise for characterizing the demography of mosquitoes and comparable insects of epidemiological and agricultural significance.


Assuntos
Aedes , Mosquitos Vetores , Animais , Feminino , Mosquitos Vetores/genética , Funções Verossimilhança , Densidade Demográfica , Larva
12.
Trans R Soc Trop Med Hyg ; 116(12): 1101-1111, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36227060

RESUMO

Sickle cell disease (SCD) affects approximately 5% of the world's population, and India has been the second highest country in the numbers of predicted SCD births. Despite the high burden in India, there is no state-led public health programme, and very few interventions dealing with the treatment and management of SCD are available. This review highlights the dearth of SCD-related interventions, and demonstrates that these interventions effectively improve patients' conditions and are feasible to implement in India. We systematically searched three databases-PubMed/Medline, Google Scholar and Web of Science-for articles from India on SCD-related interventions. The PRISMA guidelines were followed during this review. We included 22 studies, of which 19 dealt with specific therapeutic interventions, and 3 with comprehensive SCD care. Hydroxyurea therapy was the main therapy in 15 studies and is efficacious. Three studies demonstrated the feasibility of comprehensive care in resource-limited settings. The low number of SCD-related intervention studies does not match the huge burden of SCD in India. Governments of endemic countries should consider the findings of available interventions and include them in their countries' programmes. Comprehensive care is feasible in India and other low-resource settings, from screening to treatment and psychosocial support.


Assuntos
Anemia Falciforme , Humanos , Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Anemia Falciforme/diagnóstico , Hidroxiureia/uso terapêutico , Índia/epidemiologia
13.
J Community Genet ; 13(6): 597-603, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36227533

RESUMO

Sickle cell disease (SCD) is a progressively debilitating genetic disease, and India is the second most affected nation in the prevalence of births with SCD. This SCD prevalence is high among Indian indigenous tribal communities, whose healthcare is pluralistic. Traditional healers are an essential part of tribal pluralistic care. This study aimed to understand the extent of SCD-related knowledge and practices of traditional healers and their willingness to participate in the SCD programme, which is primarily meant to screen and treat SCD. Following the grounded theory approach, data were collected by in-depth interviews with 40 traditional healers selected from five SCD endemic districts. Text data were coded through a deductive approach, and thematic content analysis was carried out. A few healers knew about SCD. However, almost all are aware of anaemia and its symptoms. Most healers were unaware of the cause of SCD and mentioned that malnutrition and anaemia are reasons for the recurrence of SCD-related symptoms. Most of the traditional healers did not give any treatment. Some gave symptomatic treatment and provided herbal medicines along with some rituals. Though some healers treated some of the typical symptoms of SCD like spleen enlargement, jaundice, swelling and pains in joints, they did not link them with SCD. All traditional healers expressed concern and said they support the government-run SCD programme. The programme should recognise the role and importance of traditional healers. Necessary education on SCD may be given to the healers. Such involvement and education empower the healers in appropriately guiding the people concerning SCD care.

14.
Development ; 149(23)2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36305490

RESUMO

Significant efforts are ongoing to develop refined differentiation protocols to generate midbrain dopamine (DA) neurons from pluripotent stem cells for application in disease modeling, diagnostics, drug screening and cell-based therapies for Parkinson's disease. An increased understanding of the timing and molecular mechanisms that promote the generation of distinct subtypes of human midbrain DA during development will be essential for guiding future efforts to generate molecularly defined and subtype-specific DA neurons from pluripotent stem cells. Here, we use droplet-based single-cell RNA sequencing to transcriptionally profile the developing human ventral midbrain (VM) when the DA neurons are generated (6-11 weeks post-conception) and their subsequent differentiation into functional mature DA neurons in primary fetal 3D organoid-like cultures. This approach reveals that 3D cultures are superior to monolayer conditions for their ability to generate and maintain mature DA neurons; hence, they have the potential to be used for studying human VM development. These results provide a unique transcriptional profile of the developing human fetal VM and functionally mature human DA neurons that can be used to guide stem cell-based therapies and disease modeling approaches in Parkinson's disease.


Assuntos
Doença de Parkinson , Células-Tronco Pluripotentes , Humanos , Doença de Parkinson/genética , Doença de Parkinson/terapia , Neurônios Dopaminérgicos , Mesencéfalo , Diferenciação Celular/genética
15.
J Migr Health ; 6: 100130, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110500

RESUMO

Background: Disparities in healthcare access to internal migrants exist, and the gaps may widen further if appropriate steps are not taken. Innovative approaches are needed to better align the healthcare services with the migrants' needs. Aim: The aim was to develop and test a supportive strategy of healthcare, which would achieve the desired level of access and delivery of maternal healthcare services to internal migrants living in nine Indian cities. Methods: This intervention with the quasi-experimental design was conducted with pre- vs post-intervention comparisons within the interventional groups and with the control group. The intervention was implemented with an inclusive partnership approach. Advocacy and community mobilization were the main intervention components. Findings: An increased proportion of women sought antenatal care during the intervention. More women initiated seeking antenatal care in the first trimester. Due to intervention, health workers' prenatal (41.7% in the post- against 14.7% in the pre-interventional phase) and postnatal home visits increased (11.6% to 34.7%) considerably. Conclusions: Interventions with inclusive partnership would improve healthcare access to vulnerable communities such as migrants. Hence, efforts to strengthen the government healthcare system through novel strategies are crucial to provide better healthcare to migrants.

16.
Stem Cell Reports ; 17(10): 2203-2219, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36150382

RESUMO

We have developed an efficient approach to generate functional induced dopaminergic (DA) neurons from adult human dermal fibroblasts. When performing DA neuronal conversion of patient fibroblasts with idiopathic Parkinson's disease (PD), we could specifically detect disease-relevant pathology in these cells. We show that the patient-derived neurons maintain age-related properties of the donor and exhibit lower basal chaperone-mediated autophagy compared with healthy donors. Furthermore, stress-induced autophagy resulted in an age-dependent accumulation of macroautophagic structures. Finally, we show that these impairments in patient-derived DA neurons leads to an accumulation of phosphorylated alpha-synuclein, the classical hallmark of PD pathology. This pathological phenotype is absent in neurons generated from induced pluripotent stem cells from the same patients. Taken together, our results show that direct neural reprogramming can be used for obtaining patient-derived DA neurons, which uniquely function as a cellular model to study age-related pathology relevant to idiopathic PD.


Assuntos
Células-Tronco Pluripotentes Induzidas , Doença de Parkinson , Adulto , Autofagia/fisiologia , Neurônios Dopaminérgicos/patologia , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Doença de Parkinson/genética , alfa-Sinucleína/genética
18.
J Proteins Proteom ; 13(2): 95-108, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572846

RESUMO

Viral infections are progressively becoming a global health burden, as witnessed in the ongoing COVID-19 pandemic. Respiratory Syncytial Virus (RSV) is another highly contagious negative-sense RNA virus that causes lower respiratory tract infections and high mortality in infants. Palivizumab (Synagis®) is the only humanized monoclonal antibody (mAb) approved by the FDA against RSV. The virus neutralization efficacy often depends on the nature and abundance of the glycoforms in therapeutic mAbs. Therefore, a thorough estimation of their PTM profile, especially glycosylation, is relevant. Here, we describe the intact and released glycan analysis of palivizumab (Synagis®) using HILIC chromatography and mass spectrometry. We detected five glycoforms (Man5/G0FB, G0F/G1F, G1F/G1F, G0FB/G0FB, and G2F/G2F) in deconvoluted MS spectra of intact glycosylated palivizumab. The mapping of the peptide and glycopeptides using LC-ESI-MS led to the detection of associated PTMs and the direct identification of a glycopeptide, GlcNAc3Man2. EEQYNSTYR, derived from the heavy chain of palivizumab.Release glycan analysis using UHPLC-HILIC revealed a typical glycan profile consisting of major glycans, G0F (33.94%), G1F (35.50%), G2F (17.24%) also reported previously and minor G1F' (5.81%), Man5 (3.96%) and G0FB (2.26%) forms with the superior resolution of isomeric G1F/G1F'. Next, we provide the first experimental evidence of Neu5Gc in the commercial palivizumab formulation using DMB labelling. The estimated monosaccharide composition was consistent with previous studies. The findings of the study highlight the efficiency of the release glycan method in providing a correct measure of the total palivizumab glycan pool compared to the intact glycoprotein/glycopeptide approach. The UHPLC-RPLC/HILIC and MS combinations provide a more comprehensive glycoprofile assessment due to the parallel use of fluorescent labels for the analysis of the release of N-glycan, sialic acid, and monosaccharide composition. This approach is suitable for quick quality testing and market surveillance of therapeutic mAbs. Alongside a well-perceived need for cost-effective immunoprophylaxis and the ongoing fast-paced development of next-generation variants of palivizumab, such as MEDI8897, the study reiterates glycosylation as a critical parameter that needs monitoring for drug characterization and quality control. Supplementary Information: The online version contains supplementary material available at 10.1007/s42485-022-00086-1.

19.
J Community Genet ; 13(3): 329-338, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35103923

RESUMO

This study reports the extent of sickle cell disease (SCD)-related knowledge and management practices of peripheral health workers located in tribal areas of India. This formative qualitative study used a grounded theory approach and collected data through in-depth interviews. It was implemented in six districts endemic to SCD. From each district, four primary health centre (PHC) areas, predominantly inhabited by tribal communities, were included. The participants were 120 peripheral health workers, in two categories-regular health workers (RHWs) and community health workers (CHWs), working in 24 PHCs. Most of the RHWs and a little lesser number of CHWs were aware of SCD, and most of them knew it as a blood disorder. About half of the health workers reported that SCD is hereditary; however, some attributed it to malnutrition and considered it anaemia. Many health workers could tell some typical symptoms of SCD, including anaemia and severe pain. None of the PHCs offered management/treatment of SCD. And none of the health workers has any expertise in managing SCD patients. However, some health workers dealt with SCD cases and provided symptomatic treatment. Though several health workers said that SCD is preventable, comprehensive knowledge on prevention was lacking. Some health workers mentioned mass screening, counselling, and creating awareness. Thus, this paper reports the inadequacy of SCD-related knowledge and management practices among health workers. Health workers should know their roles and capabilities in managing SCD. They should be provided in-service, regular, and structured training programmes as part of the comprehensive SCD programme.

20.
CNS Neurol Disord Drug Targets ; 21(1): 62-76, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33719979

RESUMO

Parkinson's Disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Though significant insights into the molecular-biochemical-cellular-behavioral basis of PD have been understood, there is no appreciable treatment available till date. Current therapies provide symptomatic relief without any influence on the progression of the disease. Stem cell therapy has been vigorously explored to treat PD. In this comprehensive review, we analyze various stem cell candidates for treating PD and discuss the possible mechanisms. We advocate the advantage of using neural crest originated Dental Pulp Stem Cells (DPSC) due to their predisposition towards neural differentiation and their potential to regenerate neurons far better than commonly used bone marrow derived mesenchymal stem cells (BM-MSCs). Eventually, we highlight the current challenges in the field and the strategies, which may be used for overcoming the impediments.


Assuntos
Polpa Dentária/transplante , Doença de Parkinson/terapia , Transplante de Células-Tronco/métodos , Células-Tronco , Animais , Diferenciação Celular , Células Cultivadas , Exossomos , Humanos , Neurônios , Ratos
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