scholarly journals Family aggregation analysis shows a possible heritable background of equine grass sickness (dysautonomia) in a Hungarian stud population

2020 ◽  
Author(s):  
Boglárka Vincze ◽  
Márta Varga ◽  
Orsolya Kutasi ◽  
Petra Zenke ◽  
Ottó Szenci ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Intestinal Microbiome ◽  
Environment Management ◽  
Grass Sickness ◽  
Increased Risk ◽  
Familial Clustering ◽  
Life Threatening ◽  
Family Aggregation ◽  
Close Relatives ◽  
Aggregation Analysis

AbstractEquine grass sickness (also known as dysautonomia) is a life-threatening polyneuropathic disease affecting horses with approx. 80% mortality. Since its first description over a century ago, several factors, such as the phenotype, intestinal microbiome, environment, management and climate, have been supposed to be associated with the increased risk of dysautonomia. In this retrospective study, we examined the possible involvement of genetic factors. Medical and pedigree datasets regarding 1,233 horses with 49 affected animals born during a 23-year period were used in the analysis. Among the descendants of some stallions, the proportion of animals diagnosed with dysautonomia was unexpectedly high. Among males, the odds of dysautonomia were found to be higher, albeit not significantly, than among females. Significant familial clustering (genealogical index of familiality, P = 0.001) was observed among the affected animals. Further subgroups were identified with significant (P < 0.001) aggregation among close relatives using kinship-based methods. Our analysis, along with the slightly higher disease frequency in males, suggests that dysautonomia may have a genetic causal factor with an X-linked recessive inheritance pattern. This is the first study providing ancestry data and suggesting a heritable component in the likely multifactorial aetiology of the disease.

scholarly journals Family aggregation analysis reveals a heritable background of equine grass sickness (dysautonomia)

2019 ◽  
Author(s):  
Boglárka Vincze ◽  
Márta Varga ◽  
András Gáspárdy ◽  
Orsolya Kutasi ◽  
Petra Zenke ◽  
...  
Keyword(s):  
Large Scale ◽  
Intestinal Microbiome ◽  
Pedigree Data ◽  
Data Set ◽  
Grass Sickness ◽  
Disease Occurrence ◽  
Increased Risk ◽  
Life Threatening ◽  
Family Aggregation ◽  
Close Relatives

AbstractEquine grass sickness (also known as dysautonomia) is a life-threatening polyneuropathic disease affecting horses with approx. 80% mortality. Since it’s first description over a hundred years ago, several factors including phenotypic, environmental, management, climate, and intestinal microbiome) have been associated with increased risk of dysautonomia. But despite the extensive research on dysautonomia, it’s causative factors have yet been identified. A retrospective pedigree and phenotype based genetic epidemiological study was performed to analyze the associations of disease occurrence and the kinship in a Hungarian large scale stud. The pedigree data set containing 1233 horses with 49 affected animals was used in the analysis. The first finding was that among the descendants of some stallions the proportion of affected animals are unexpectedly high, with a maximum of 25% of a stallions descendants affected. Animals with affected siblings have higher odds to be a case (OR: 1.27, 95% CI: 1.01-1.57, p=0.033). Among males in the affected population the odds of dysautonomia is higher than in females (OR: 1.76, 95% CI: 0.95-3.29, p=0.057). Significant familial clustering was observed among the affected animals (GIF p=0.001). Further subgroups were identified with significant (p<0.001) aggregation among close relatives using kinship-based methods. Our analysis of the data and the observed higher disease frequency in males suggests that dysautonomia may have X-linked recessive inheritance as a causal factor. This is the first study providing ancestry data and suggesting a genetic contribution to the likely multifactorial causes of the disease.

scholarly journals Relative risk for Alzheimer disease based on complete family history

Neurology ◽  
2019 ◽  
Vol 92 (15) ◽  
pp. e1745-e1753 ◽  
Author(s):  
Lisa A. Cannon-Albright ◽  
Norman L. Foster ◽  
Karen Schliep ◽  
James M. Farnham ◽  
Craig C. Teerlink ◽  
...  
Keyword(s):  
Relative Risk ◽  
Family History ◽  
Alzheimer Disease ◽  
Genetic Factors ◽  
Population Based ◽  
Death Certificates ◽  
Age At Death ◽  
Increased Risk ◽  
Improve Accuracy ◽  
Close Relatives

ObjectiveThe inherited component for Alzheimer disease (AD) risk has focused on close relatives; consideration of the full family history may improve accuracy and utility of risk estimates.MethodsA population resource including a genealogy of Utah pioneers from the 1800s linked to Utah death certificates was used to estimate relative risk for AD based on specific family history constellations, including from first- to third-degree relatives.ResultsAny affected first-degree relatives (FDR) significantly increased risk of AD (≥1 FDRs: relative risk [RR] 1.73, 95% confidence interval [CI] [1.59–1.87]; ≥2 FDRs: RR 3.98 [3.26–4.82]; ≥3 FDRs: RR 2.48 [1.07–4.89]; ≥4 FDRs: RR 14.77 [5.42–32.15]). Affected second-degree relatives (SDR) increased risk even in the presence of affected FDRs (FDR = 1 with SDR = 2: RR 21.29 [5.80–54.52]). AD only in third-degree relatives (TDR) also increased risk (FDR = 0, SDR = 0, TDR ≥3: RR 1.43 [1.21–1.68]). Mixed evidence was observed for differences in risk based on maternal compared to paternal inheritance; higher risks for men than women with equivalent family history, and higher risk for individuals with at least one affected FDR regardless of the relative's age at death, were observed.ConclusionsThis population-based estimation of RRs for AD based on family history ascertained from extended genealogy data indicates that inherited genetic factors have a broad influence, extending beyond immediate relatives. Providers should consider the full constellation of family history when counseling patients and families about their risk of AD.

Molecular Evaluation of MicroRNA-146 Gene Variability (rs2910164 C> G) and its Association with Increased Susceptibility to Coronary Artery Disease

MicroRNA ◽  
2020 ◽  
Vol 09 ◽  
Author(s):  
Rashid Mir ◽  
Imadeldin Elfaki ◽  
Chandan k Jha ◽  
Jamsheed Javid ◽  
Suriya Rehman ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Factors ◽  
Mirna Gene ◽  
Amplification Refractory Mutation System ◽  
Coronary Artery Diseases ◽  
Increased Risk ◽  
Inheritance Model ◽  
Artery Disease ◽  
Increased Susceptibility

Aim: Apart from the modifiable risk factors, genetic factors are believed to also influence the outcome of the coronary artery diseases (CAD). Under the genetic factors, miRNA polymorphisms, namely Hsa-miR-146a-5p (rs2910164) have become an important tool to study the mechanism that underlies the pathogenesis of this disease. Therefore, we investigated the association of miR-146a gene variations with susceptibility of coronary artery diseases. Methodology: This study was conducted on 100 CAD patients and 117 matched healthy individuals. Genotyping of the Hsa-miR-146a-5p C>G gene variation was performed by using amplification refractory mutation system PCR method (ARMS-PCR). Results: The distribution of Hsa-miR-146a-5p rs2910164 C>G genotypes observed between patients and controls was significantly different (P=0.048). Moreover, the frequency of G allele (fG) was found to be significantly higher among patients than in controls (0.36 vs. 0.25). Our findings showed that the Hsa-miR-146a-5p C>G variant was associated with an increased risk of CAD in codominant inheritance model CC vs. CG genotype (OR = 1.84, 95 % CI, 1.02-3.31; p=0.040) and (OR = 3.18, 95 % CI, 1.02-9.9; p=0.045) for CC vs. GG genotype in dominant inheritance model. Whereas the G allele significantly increased the risk of coronary artery disease (OR =1,81, 95 % CI, 1.18-2.78; p=0.006) compared to C allele. Taken together, these results demonstrated that miR-146a/rs2910164 is associated with susceptibility to coronary artery disease, providing novel insights into the genetic etiology and underlying biology of coronary artery disease. Conclusion: Our findings indicated that Hsa-miR-146a-5p rs2910164 GG genotype and G allele are associated with an increased susceptibility to Coronary Artery Disease. A larger sample size can be the key to progress in establishing the genetic co-relation of miRNA gene polymorphisms and cardiovascular diseases.

scholarly journals Immunogenetic Predictors of Severe COVID-19

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 211
Author(s):  
Anna Malkova ◽  
Dmitriy Kudlay ◽  
Igor Kudryavtsev ◽  
Anna Starshinova ◽  
Piotr Yablonskiy ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Virus Disease ◽  
Analysis Data ◽  
Published Data ◽  
Diagnostic Significance ◽  
Life Threatening ◽  
Coronavirus Infection ◽  
Angiotension Converting Enzyme ◽  
Related Proteins

According to an analysis of published data, only 20% of patients with the new coronavirus infection develop severe life-threatening complications. Currently, there are no known biomarkers, the determination of which before the onset of the disease would allow assessing the likelihood of its severe course. The purpose of this literature review was to analyze possible genetic factors characterizing the immune response to the new coronavirus infection that could be associated with the expression of angiotension-converting enzyme 2 (ACE-2) and related proteins as predictors of severe Corona virus disease 2019 (COVID-19). We analyzed original articles published in Medline, PubMed and Scopus databases from December 2019 to November 2020. For searching articles, we used the following keywords: New coronavirus infection, Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), COVID-19, severe course, complications, thrombosis, cytokine storm, ACE-2, biomarkers. In total, 3714 publications were selected using the keywords, of which 8 were in congruence with all the criteria. The literature analysis of the association of immunogenic characteristics and the expression of ACE-2 and related proteins with the development of severe COVID-19 revealed following genetic factors: HLA-B*46:01 genotype, CXCR6 gene hypoexpression, CCR9 gene expression, TLR7, rs150892504 mutations in the ERAP2 gene, overexpression of wild-type ACE-2, TMPRSS2 and its different polymorphisms. Genes, associated with the severe course, are more common among men. According to the analysis data, it can be assumed that there are population differences. However, the diagnostic significance of the markers described must be confirmed with additional clinical studies.

Safety and Efficacy of Argatroban in the Management of Heparin-Induced Thrombocytopenia

2011 ◽  
Vol 4 ◽  
pp. CMBD.S5118 ◽  
Author(s):  
Bernd Saugel ◽  
Roland M. Schmid ◽  
Wolfgang Huber
Keyword(s):  
Arterial Thrombosis ◽  
Pharmacokinetic Profile ◽  
The United States ◽  
Heparin Therapy ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Heparin Induced Thrombocytopenia ◽  
Safety And Efficacy ◽  
Increased Risk ◽  
Life Threatening

Heparin-induced thrombocytopenia (HIT) is a life-threatening adverse reaction to heparin therapy that is characterized by thrombocytopenia and an increased risk of venous and arterial thrombosis. According to guidelines, in patients with strongly suspected or confirmed HIT all sources of heparin have to be discontinued and an alternative, nonheparin anticoagulant for HIT treatment must immediately be started. For both the prophylaxis of thrombembolic events in HIT and the treatment of HIT with thrombosis the direct thrombin inhibitor argatroban is approved in the United States. The objective of this review is to describe the mechanism of action and the pharmacokinetic profile of argatroban, to characterize argatroban regarding its safety and therapeutic efficacy and to discuss its place in therapy in HIT.

Cancer and COVID-19: A proposed mechanism with therapeutic interventions.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3135-3135
Author(s):  
Yan Leyfman ◽  
Nancy Emmanuel ◽  
Aleksey Tentler ◽  
Jared Cappelli ◽  
Timothy K Erick ◽  
...  
Keyword(s):  
Respiratory Illness ◽  
Organ Damage ◽  
Multiple Organ ◽  
Therapeutic Interventions ◽  
Actual Number ◽  
Data Registry ◽  
Number Of Patients ◽  
Increased Risk ◽  
Life Threatening ◽  
Active Cancer

3135 Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus that causes the respiratory illness coronavirus disease 2019 (COVID-19). COVID-19 ranges in severity from an asymptomatic viral infection to life-threatening cases of pneumonia, acute respiratory distress syndrome (ARDS), multi-organ damage and sepsis. Cancer patients are at an increased risk of severe SARS-CoV-2 infection due to their immunocompromised status. We propose a mechanism by which SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation and hypoxia-induced cellular metabolic alterations leading to cell death. Hypoxia is also induced by malignancy due to alterations in metabolism, resulting in greater IL-6 secretion. Methods: To highlight the possible effect of active cancer on the likelihood of hypoxia in COVID-19, we analyzed the correlation between cancer status and the severity of COVID-19 from the COVID-19 and Cancer Consortium data registry. For cancer status, we looked at progressive cancer and remission of cancer only -- those being the two extremes of presence and absence of uncontrolled cancer. Similar to prior studies, the severity of COVID-19 was used as an indication of hypoxia. Results: We observed a 24% positive deviation between expected and actual number of patients with actively progressing cancer who had hypoxic COVID-19 (moderate to severe), and a 26.9% negative deviation between expected and actual number of patients with active cancer who had no hypoxia with COVID-19 (p<0.0001). Conversely, for patients with cancer in remission, there was only a +5.8% and -5.1% deviation between expected and actual number of patients who did not have hypoxia and who had hypoxia, respectively. Conclusions: These results suggest that in the presence of poorly controlled malignancy, there is an increased likelihood of hypoxia in patients with COVID-19, thereby exacerbating downstream cytokine release syndrome and contributing to prolonged systemic inflammatory injury. Appreciating this pathway, future therapies can be developed to target the pathogenesis of both diseases and prevent progression, as seen with mesenchymal stem cells, which demonstrated a 91% overall survival and 100% survival in patients younger than 85 years old at one month after a single treatment.[Table: see text]

Risk factors for heat-related illnesses during the Hajj mass gathering: an expert review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Saber Yezli
Keyword(s):  
Preventive Measures ◽  
Febrile Illness ◽  
Mass Gatherings ◽  
Expert Review ◽  
Hot Environment ◽  
Increased Risk ◽  
Modifiable Factors ◽  
Life Threatening ◽  
Nutrition And Hydration ◽  
And Behavior

Abstract Human exposure to a hot environment may result in various heat-related illnesses (HRIs), which range in severity from mild and moderate forms to life-threatening heatstroke. The Hajj is one of the largest annual mass gatherings globally and has historically been associated with HRIs. Hajj attracts over two million Muslim pilgrims from more than 180 countries to the holy city of Makkah, Kingdom of Saudi Arabia. Several modifiable and non-modifiable factors render Hajj pilgrims at increased risk of developing HRIs during Hajj. These include characteristics of the Hajj, its location, population, and rituals, as well as pilgrims’ knowledge of HRIs and their attitude and behavior. Makkah is characterized by a hot desert climate and fluctuating levels of relative humidity. Pilgrims are very diverse ethnically and geographically, with different adaptations to heat. Significant proportions of the Hajj population are elderly, obese, and with low levels of fitness. In addition, many have underlying health conditions and are on multiple medications that can interfere with thermoregulation. Other factors are inherent in the Hajj and its activities, including crowding, physically demanding outdoor rituals, and a high frequency of infection and febrile illness. Pilgrims generally lack awareness of HRIs, and their uptake of preventive measures is variable. In addition, many engage in hazardous behaviors that increase their risk of HRIs. These include performing rituals during the peak sunshine hours with no sun protection and with suboptimal sleep, nutrition, and hydration, while neglecting treatment for their chronic conditions. HRIs preventive plans for Hajj should incorporate measures to address the aforementioned factors to reduce the burden of these illnesses in future Hajj seasons. Lessons from the Hajj can be used to inform policy making and HRIs preventive measures in the general population worldwide.

scholarly journals COVID-19 Infection with Refractory Diabetic Ketoacidosis- A case Report

2021 ◽  
Vol 7 (2) ◽  
pp. 54-56
Author(s):  
Reshmi Mishra ◽  
◽  
Jyoti Ranjan Behera ◽  
P. Ramkumar ◽  
Mukesh Kumar Jain ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Metabolic Acidosis ◽  
Diabetic Ketoacidosis ◽  
Vital Organ ◽  
Increased Risk ◽  
Life Threatening ◽  
Life Threatening Complication ◽  
New Onset

Diabetic ketoacidosis is an acute life-threatening complication of type 1 diabetes. Sometimes it is the first presentation in an undiagnosed child. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) and diabetes mellitus are very much interrelated as diabetes mellitus is associated with an increased risk of severe COVID19 at the same time, many cases of new-onset diabetes had been diagnosed. Hyperglycemia, metabolic acidosis, and ketonemia are classical presentations. It is essential to correct the acidosis and fluid correction and insulin therapy in these patients, leading to vital organ dysfunction. In refractory metabolic acidosis, renal replacement therapy may help

scholarly journals Non-traumatic Tension Gastrothorax: A Potential Mimicker of Tension Pneumothorax

2021 ◽  
Vol 15 (8) ◽  
pp. 1-7
Author(s):  
Jonathan D. Pierce ◽  
Neal R. Shah ◽  
Ata A. Rahnemai-Azar ◽  
Amit Gupta
Keyword(s):  
Clinical Presentation ◽  
Tension Pneumothorax ◽  
Accurate Diagnosis ◽  
Imaging Features ◽  
Elderly Female ◽  
Hemodynamic Compromise ◽  
Mediastinal Shift ◽  
Increased Risk ◽  
Life Threatening ◽  
Tension Gastrothorax

Tension gastrothorax is a rare, life-threatening clinical condition caused by intrathoracic herniation of the stomach through a diaphragmatic defect which becomes increasingly distended over time. If not recognized promptly, this can rapidly progress to respiratory distress, mediastinal shift, and hemodynamic compromise. Initial clinical presentation and imaging findings closely mirror those of tension pneumothorax, confounding diagnosis and potentially leading to unnecessary interventions with increased risk of morbidity and mortality. Here, we present a case of an elderly female who presented with a non-traumatic tension gastrothorax and a review of key imaging features and strategies to aid in recognition and accurate diagnosis of this emergent clinical entity.

scholarly journals Maternal Near Miss in Patients with Systemic Lupus Erythematosus

2021 ◽  
Author(s):  
Arlley Cleverson Belo Silva ◽  
Sue Yazaki Sun ◽  
Felipe Favorette Campanharo ◽  
Letícia Tiemi Morooka ◽  
José Guilherme Cecatti ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Maternal Death ◽  
Lupus Erythematosus ◽  
Neonatal Death ◽  
Near Miss ◽  
Maternal Near Miss ◽  
Control Group ◽  
Systemic Lupus ◽  
Increased Risk ◽  
Life Threatening

Abstract Introduction: Systemic lupus erythematosus (SLE) may cause irreversible organ damage. Pregnancy with coexisting SLE may have severe life-threatening risks. Severe maternal morbidities (SMM) include maternal death, maternal near miss (MNM), and potentially life-threatening conditions (PLTC). This study aimed to determine the prevalence of SMM in patients with SLE and analyze the parameters that contributed to cases of greater severity. Methods: This is a cross-sectional retrospective study from analysis of data retrieved from medical records of pregnant women with SLE treated at São Paulo Hospital , Brazil, from 2005 to 2015. The pregnant women were divided in control group without complications, group with PLTC, and group with MNM. Results: Out of 149 pregnancies, there were 14 cases of MNM (9.4%), 56 cases of PLTC (37.6%), and no maternal death. The maternal near miss rate was 112.9 per 1,000 live births. The majority of PLTC (83.9%) and MNM (92.9%) cases had preterm deliveries with statistically significant increased risk compared with control group [p=0.0042; OR (95% CI): 12.05 (1.5-96.6) for MNM group and p=0.0001; OR (95% CI): 4.84 (2.2-10.8) for PLTC group]. SMM increases the risk of longer hospitalization [p<0,0001; OR (95% CI): 18.8 (7.0-50.6) and p <0.0001; OR (95% CI): 158.17 (17.6-1424,2) for PLTC and MNM, respectively], newborns with low birth weight [p=0.0006; OR (95% CI): 3.67 (1.7-7.9) and p=0.0009; OR (95% CI): 17.68 (2-153.6) for PLTC and MNM group, respectively] as well as renal diseases [PLTC (58.9%, 33/56; p = 0.0069) and MNM (78.6%, 11/14; p = 0.0026)]. MNM cases presented increased risk for neonatal death [p=0.0128; OR (95% CI): 38.4 (3.3-440.3)], stillbirth and miscarriage [p=0.0011; OR (95% CI): 7.68 (2.2-26.3)]. Conclusion: SLE was significantly associated with severe maternal morbidity, longer hospitalizations, and increased risk of poor obstetric and neonatal outcomes, such as prematurity, neonatal death, miscarriage and fetal loss.

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