The Role of Immunogenetics in COVID-19

Coronavirus disease 2019 (COVID-19) is induced by SARS-CoV-2 and may arise as a variety of clinical manifestations, ranging from an asymptomatic condition to a life-threatening disease associated with cytokine storm, multiorgan and respiratory failure. The molecular mechanism behind such variability is still under investigation. Several pieces of experimental evidence suggest that genetic variants influencing the onset, maintenance and resolution of the immune response may be fundamental in predicting the evolution of the disease. The identification of genetic variants behind immune system reactivity and function in COVID-19 may help in the elaboration of personalized therapeutic strategies. In the frenetic look for universally shared treatment plans, those genetic variants that are common to other diseases/models may also help in addressing future research in terms of drug repurposing. In this paper, we discuss the most recent updates about the role of immunogenetics in determining the susceptibility to and the history of SARS-CoV-2 infection. We propose a narrative review of available data, speculating about lessons that we have learnt from other viral infections and immunosenescence, and discussing what kind of aspects of research should be deepened in order to improve our knowledge of how host genetic variability impacts the outcome for COVID-19 patients.

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Physiology of Nucleoside Transporters: Back to the Future. . . .

Physiology ◽

10.1152/physiol.00036.2007 ◽

2008 ◽

Vol 23 (1) ◽

pp. 41-48 ◽

Cited By ~ 29

Author(s):

Jennifer B. Rose ◽

Imogen R. Coe

Keyword(s):

Viral Infections ◽

Drug Efficacy ◽

Structure And Function ◽

Nucleoside Transporters ◽

Integral Membrane Proteins ◽

Future Research ◽

The Everyday ◽

And Function ◽

The Relationship

Nucleoside transporters (NTs) are integral membrane proteins responsible for mediating and facilitating the flux of nucleosides and nucleobases across cellular membranes. NTs are also responsible for the uptake of nucleoside analog drugs used in the treatment of cancer and viral infections, and they are the target of certain compounds used in the treatment of some types of cardiovascular disease. The important role of NTs as drug transporters and therapeutic targets has necessarily led to intense interest into their structure and function and the relationship between these proteins and drug efficacy. In contrast, we still know relatively little about the fundamental physiology of NTs. In this review, we discuss various aspects of the physiology of NTs in mammalian systems, particularly noting tissues and cells where there has been little recent research. Our central thesis is reference back to some of the older literature, combined with current findings, will provide direction for future research into NT physiology that will lead to a fuller understanding of the role of these intriguing proteins in the everyday lives of cells, tissues, organs, and whole animals.

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EXPRESS: Pulmonary Hypertension Associated With Neurofibromatosis Type 2

Pulmonary Circulation ◽

10.1177/20458940211029550 ◽

2021 ◽

pp. 204589402110295

Author(s):

Hirohisa Taniguchi ◽

Tomoya Takashima ◽

Ly Tu ◽

RaphaÃ«l Thuillet ◽

Asuka Furukawa ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Neurofibromatosis Type ◽

Pulmonary Vascular Remodeling ◽

Life Threatening ◽

History Of ◽

Pulmonary Arterial ◽

First Time

Although precapillary pulmonary hypertension (PH) is a rare but severe complication of patients with neurofibromatosis type 1 (NF1), its association with NF2 remains unknown. Herein, we report a case of a 44-year-old woman who was initially diagnosed with idiopathic pulmonary arterial hypertension (IPAH) and treated with PAH-specific combination therapy. However, a careful assessment for a relevant family history of the disease and genetic testing reveal that this patient had a mutation in the NF2 gene. Using immunofluorescence and Western blotting, we demonstrated a decrease in endothelial NF2 protein in lungs from IPAH patients compared to control lungs, suggesting a potential role of NF2 in PAH development. To our knowledge, this is the first time that precapillary PH has been described in a patient with NF2. The altered endothelial NF2 expression pattern in PAH lungs should stimulate work to better understand how NF2 is contributing to the pulmonary vascular remodeling associated to these severe life-threatening conditions.

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Diagnosis Based on Detection of CXCL10 in Urine as Biomarker for The Determining Diagnosis of Active Lung Tuberculosis

Indonesian Journal of Tropical and Infectious Disease ◽

10.20473/ijtid.v9i1.22160 ◽

2021 ◽

Vol 9 (1) ◽

pp. 57

Author(s):

Ni Made Mertaniasih ◽

I Gede Yogi Prema Ananda ◽

Soedarsono Soedarsono ◽

Deby Kusumaningrum

Keyword(s):

Clinical Manifestations ◽

Cross Sectional Study ◽

Urine Samples ◽

Laboratory Research ◽

Future Research ◽

Cross Sectional ◽

Pulmonary Tb ◽

Lung Tuberculosis ◽

History Of ◽

Tuberculosis Diagnosis

Tuberculosis diagnosis is an important component in decreasing TB incidence and prevalence. Because of the difficulty to collect sputum in some cases, urine specimens are used as it is easier to garner. One of the biomarkers in urine that can be used to diagnose pulmonary TB is IP-10, which can be represented by the CXCL10 gene. The study aims to determine the accuracy of diagnosis based on detection of the CXCL10 gene in urine as a biomarker for the patients with suspected pulmonary TB in Dr. Soetomo Hospital in Surabaya from November 2019 until March 2020. Thus, this is an observative laboratory research with a cross-sectional study. CXCL10 gene was examined using PCR for 36 urine samples, and then, the data, together with the medical records of clinical manifestations of pulmonary TB, GeneXpert MTB /RIF, blood count, and thorax radiograph, were processed using IBM SPSS Statistics 26. The results of the GeneXpert MTB/RIF and thorax radiograph criteria show positive results of pulmonary TB, which were 44.4% and 69.4% respectively. CXCL10 gene was not found in all urine of healthy people (negative), while 2.8% (1/36 samples) positive CXCL10 gene was found in a patient with positive GeneXpert, also with negative clinical manifestations and urine culture. In this study, the accuracy of diagnosis based on detection of the CXCL10 gene in urine for diagnosis of active pulmonary TB was 2.8%. Future research is needed to improve the methods, among them are bigger size of urine samples and clearer medical history of patients.

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Using Tertiary Sulci to Map the “Cognitive Globe” of Prefrontal Cortex

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_01696 ◽

2021 ◽

pp. 1-18

Author(s):

Jacob A. Miller ◽

Mark D'Esposito ◽

Kevin S. Weiner

Keyword(s):

Prefrontal Cortex ◽

Frontal Lobe ◽

Spatial Scales ◽

Structure And Function ◽

Future Research ◽

Functional Relationships ◽

Theoretical Perspectives ◽

Individual Participant ◽

And Function

Stuss considered the human prefrontal cortex (pFC) as a “cognitive globe” [Stuss, D. T., & Benson, D. F. Neuropsychological studies of the frontal lobes. Psychological Bulletin, 95, 3–28, 1984] on which functions of the frontal lobe could be mapped. Here, we discuss classic and recent findings regarding the evolution, development, function, and cognitive role of shallow indentations or tertiary sulci in pFC, with the goal of using tertiary sulci to map the “cognitive globe” of pFC. First, we discuss lateral pFC (LPFC) tertiary sulci in classical anatomy and modern neuroimaging, as well as their development, with a focus on those within the middle frontal gyrus. Second, we discuss tertiary sulci in comparative neuroanatomy, focusing on primates. Third, we summarize recent findings showing the utility of tertiary sulci for understanding structural–functional relationships with functional network insights in ventromedial pFC and LPFC. Fourth, we revisit and update unresolved theoretical perspectives considered by C. Vogt and O. Vogt (Allgemeinere ergebnisse unserer hirnforschung. Journal für Psychologie und Neurologie, 25, 279–462, 1919) and F. Sanides (Structure and function of the human frontal lobe. Neuropsychologia, 2, 209–219, 1964) that tertiary sulci serve as landmarks for cortical gradients. Together, the consideration of these classic and recent findings indicate that tertiary sulci are situated in a unique position within the complexity of the “cognitive globe” of pFC: They are the smallest and shallowest of sulci in pFC, yet can offer insights that bridge spatial scales (microns to networks), modalities (functional connectivity to behavior), and species. As such, the map of tertiary sulci within each individual participant serves as a coordinate system specific to that individual on which functions may be further mapped. We conclude with new theoretical and methodological questions that, if answered in future research, will likely lead to mechanistic insight regarding the structure and function of human LPFC.

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Recurrent hypoglycaemia and dilated cardiomyopathy: delayed presentation of Sheehan’s syndrome

BMJ Case Reports ◽

10.1136/bcr-2021-242747 ◽

2021 ◽

Vol 14 (6) ◽

pp. e242747

Author(s):

Archita Makharia ◽

Manoj Lakhotia ◽

Vineet Tiwari ◽

Kishan Gopal

Keyword(s):

Dilated Cardiomyopathy ◽

Clinical Manifestations ◽

Diabetic Woman ◽

Delayed Presentation ◽

Sheehan’S Syndrome ◽

Life Threatening ◽

History Of ◽

Sheehan's Syndrome ◽

Ischaemic Necrosis ◽

Recurrent Hypoglycaemia

Sheehan’s syndrome (SS) is ischaemic necrosis of the pituitary gland due to massive postpartum haemorrhage. The clinical manifestations may vary from subtle to life-threatening and may present immediately after delivery or many years later. We present a case history of a 58-year-old non-diabetic woman who had undetected SS and presented with two unusual manifestations, including recurrent hypoglycaemia and dilated cardiomyopathy 34 years after delivery. The dilated cardiomyopathy reversed partially after treatment.

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Update on α1-antitrypsin deficiency

Breathe ◽

10.1183/20734735.015018 ◽

2018 ◽

Vol 14 (2) ◽

pp. e17-e24 ◽

Cited By ~ 3

Author(s):

Ilaria Ferrarotti ◽

Stefania Ottaviani ◽

Annalisa De Silvestri ◽

Angelo G. Corsico

Keyword(s):

Clinical Manifestations ◽

Lung Damage ◽

Exacerbation Rate ◽

Damage Progression ◽

Appropriate Treatment ◽

Antitrypsin Deficiency ◽

History Of ◽

Randomised Controlled ◽

To Receive

α1-Antitrypsin deficiency (AATD) is an inherited metabolic disorder in which mutations in the coding sequence of the SERPINA1 gene prevent secretion of α1-antitrypsin (α1-AT) and cause predisposition to pulmonary and liver diseases. The heterogeneity of clinical manifestations in AATD is related to the complexity of biological function of α1-AT. The role of smoking is crucial in the natural history of lung damage progression in severe AATD individuals, even if it also partly explains the heterogeneity in lung disease. Lung damage progression in AATD can also be related to body mass index, exacerbation rate, sex, environmental exposure and specific mutations of SERPINA1. Recent randomised controlled trials, together with previous observational work, have provided compelling evidence for the importance of early detection and intervention in order to enable patients to receive appropriate treatment and preserve functional lung tissue.

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Religion and Spirituality in Surgery

10.1093/med/9780190272432.003.0007 ◽

2017 ◽

Author(s):

John Tarpley ◽

Margaret Tarpley

Keyword(s):

Coping Skills ◽

Early History ◽

Intercessory Prayer ◽

Religion And Spirituality ◽

Research Topics ◽

Faith Leaders ◽

History Of ◽

Treatment Plans

The influence of religion and spirituality (R/S) on surgeons dates back to the early history of modern surgery and continues into the 21st century. Research topics include intercessory prayer (IP), social cohesion, coping strategies, the role of chaplains and other clergy or faith leaders, and communal activities such as worship. While evidence for benefits of practices such as IP are inconclusive, patients involved in R/S activities or who hold R/S beliefs appear to have improved coping skills and quality of life (QOL). Although R/S has proven value for patients and surgeons, lack of R/S training is a barrier to surgeon involvement in addressing R/S issues such as operative procedures, treatment plans, organ donation, and end-of-life (EOL) situations. Increased training at the undergraduate, graduate, and post-graduate medical levels concerning R/S would provide surgeons and physician colleagues with skills and greater comfort in discussing these issues with patients and families. .

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Children Who Have Murdered

Medico-Legal Journal ◽

10.1177/002581727504300103 ◽

1975 ◽

Vol 43 (1) ◽

pp. 20-24 ◽

Cited By ~ 2

Author(s):

K. S. Walsh-Brennan

Keyword(s):

Social Behaviour ◽

Future Research ◽

Personality Factors ◽

Parental Alcoholism ◽

Working Mother ◽

Normal Intelligence ◽

Criminal Convictions ◽

History Of

An analysis of 11 children convicted of homicide, one girl and ten boys, indicates a maternal over-dominant relationship in eight of the males studied. The murderers were Found to have more co-operative personalities than other children Found guilty of non-capital offences and showed both normal intelligence and personality factors. Despite a history of ‘blackouts' in several cases, all were Found on investigation to be free from both major and minor epilepsy. Difficulty was experienced in determining the presence or absence of parental alcoholism, promiscuity and criminal convictions. All of the ten boys and the girl came from normal homes and apart from minor offences none were involved previously in serious anti-social behaviour. Future research is indicated on two aspects: role of the working mother with particular reference to maternal dominance, and the ‘Cycle of Deprivation Theory’.

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Dengue Virus and the Relationship with MicroRNAs

Dengue Fever in a One Health Perspective ◽

10.5772/intechopen.92453 ◽

2020 ◽

Author(s):

Samir Casseb ◽

Karla de Melo

Keyword(s):

Dengue Virus ◽

Viral Infection ◽

Viral Infections ◽

Immune Defense ◽

Tropical Regions ◽

Denv Serotypes ◽

History Of ◽

Infection Processes ◽

The Relationship

Dengue is an acute febrile disease caused by a virus of the genus Flavivirus, family Flaviviridae, endemic in tropical regions of the globe. The agent is a virus with single-stranded RNA, classified into four distinct dengue virus (DENV) serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The host’s innate and adaptive immune responses play an essential role in determining the natural history of viral infections, especially in dengue. In this context, it has observed in recent years that the presence of RNA interference (RNAi) in viral infection processes is increasing, as well as immune defense. The context microRNAs (miRNAs) go for stood out, as their presence during viral infection, both in the replication of the virus and in the defense against these infections, becomes increasingly noticeable, therefore, making it increasingly necessary to better understand the role of these small RNAs within viral infection by DENV and what their consequences are in aggravating the consequences of patients affected by this disease.

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Genealogy and Governmentality

Journal of the Philosophy of History ◽

10.1163/187226308x336001 ◽

2008 ◽

Vol 2 (3) ◽

pp. 363-396 ◽

Cited By ~ 11

Author(s):

Thomas Biebricher

Keyword(s):

Final Section ◽

Historical Narrative ◽

Future Research ◽

Historical Contingency ◽

Measuring Device ◽

Future Research Agenda ◽

History Of ◽

Governmentality Studies ◽

The Impact

AbstractThe essay aims at an assessment of whether and to what extent the history of governmentality can be considered to be a genealogy. To this effect a generic account of core tenets of Foucauldian genealogy is developed. The three core tenets highlighted are (1) a radically contingent view of history that is (2) expressed in a distinct style and (3) highlights the impact of power on this history. After a brief discussion of the concept of governmentality and a descriptive summary of its history, this generic account is used as a measuring device to be applied to the history of governmentality. While both, the concept of governmentality and also its history retain certain links to genealogical precepts, my overall conclusion is that particularly the history of governmentality (and not necessarily Foucault's more programmatic statements about it) departs from these precepts in significant ways. Not only is there a notable difference in style that cannot be accounted for entirely by the fact that this history is produced in the medium of lectures. Aside from a rather abstract consideration of the importance of societal struggles, revolts and other forms of resistance, there is also little reference to the role of these phenomena in the concrete dynamics of governmental shifts that are depicted in the historical narrative. Finally, in contrast to the historical contingency espoused by genealogy and the programmatic statements about governmentality, the actual history of the latter can be plausibly, albeit unsympathetically, read in a rather teleological fashion according to which the transformations of governmentality amount to the unfolding of an initially implicit notion of governing that is subsequently realised in ever more consistent ways. In the final section of the essay I turn towards the field of governmentality studies, arguing that some of the more problematic tendencies in this research tradition can be traced back to Foucault's own account. In particular, the monolithic conceptualisation of governmentality and the implicit presentism of an excessive focus on Neoliberalism found in many of the studies in governmentality can be linked back to problems in Foucault's own history of governmenality. The paper concludes with suggestions for a future research agenda for the governmentality studies that point beyond Foucault's own account and its respective limitations.

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