A pharmacogenetic study of perampanel: association between rare variants of glutamate receptor genes and outcomes

Introduction: The selection of antiseizure medication usually requires a trial-and-error process. Our goal is to investigate whether genetic markers can predict the outcome of perampanel (PER) use in patients with epilepsy.Method: The studied participants were selected from our previous epilepsy genetics studies where whole exome sequencing was available. We reviewed the medical records of epilepsy patients older than 20 years old treated with PER. The outcome of PER treatment included the response to PER, the occurrence of any adverse drug reaction (ADR), the presence of behavior ADR, and the ability to adhere to PER for more than 1 year. We investigated the association between the rare variants of the glutamate receptor genes and the outcomes of PER use.Result: A total of 83 patients were collected. The gene group burden analysis showed that enriched genetic variants of the glutamate receptor gene group were statistically significantly associated with the occurrence of ADR, while the glutamate ionotropic receptor delta type subunit had a nominal association with the occurrence of ADR. The gene collapse analysis found that GRID1 had a nominal association with the occurrence of ADR and GRIN3A had a nominal association with the occurrence of behavior ADR. However, these nominal associations did not remain statistically significant once adjusted for multiple testing.Discussion: We found that enriched rare genetic variants of the glutamate receptor genes were associated with the occurrence of ADR in patients taking PER. In the future, combining the results of various pharmacogenetic studies may lead to the development of prediction tools for the outcome of antiseizure medications

Colorectal Cancer Risk Perceptions in Black Men

Background: Black Americans have the greatest colorectal cancer (CRC) incidence and mortality rates in the United States. Suboptimal CRC screening rates may be mediated by health literacy, a lack of knowledge about the screening benefits and influenced by health services factors. We examined the relationship between CRC risk perceptions and socio-demographic characteristics, disease prevention activities, and personal/family history of CRC among Black men. Methods: The cross-sectional survey used a self-administered questionnaire and was conducted in five cities in the State of Florida between April 2008 and October 2009. Of the total 425 participants, 331 responses were valid for analysis. Descriptive statistics and logistic regression were performed. Results: Of 331 participants, higher CRC risk perceptions were exhibited among those aged ≥60 years (70.5%) and American nativity (59.1%). Multivariate analyses found men aged ≥60 had three times greater odds of having higher CRC risk perceptions compared to those ≤ 49 years. Obese participants had more than four times the odds and over-weight subjects had more than twice the odds as compared to healthy weight/underweight participants, to have higher CRC risk perceptions. Men with a personal/family history of CRC also had greater odds of having higher CRC risk perceptions (OR = 9.18; 95% CI = 2.02-41.79). Conclusion: Given early-onset of CRC in Black men, community educational programs tailored to Black men are needed to improve CRC screening uptake. This information will inform culturally resonate health promotion interventions to elevate CRC risk perceptions and increase screening in Black men

Leukocyte nucleus segmentation and nucleus lobe counting

<p>Abstract</p> <p>Background</p> <p>Leukocytes play an important role in the human immune system. The family of leukocytes is comprised of lymphocytes, monocytes, eosinophils, basophils, and neutrophils. Any infection or acute stress may increase or decrease the number of leukocytes. An increased percentage of neutrophils may be caused by an acute infection, while an increased percentage of lymphocytes can be caused by a chronic bacterial infection. It is important to realize an abnormal variation in the leukocytes. The five types of leukocytes can be distinguished by their cytoplasmic granules, staining properties of the granules, size of cell, the proportion of the nuclear to the cytoplasmic material, and the type of nucleolar lobes. The number of lobes increased when leukemia, chronic nephritis, liver disease, cancer, sepsis, and vitamin B12 or folate deficiency occurred. Clinical neutrophil hypersegmentation has been widely used as an indicator of B12 or folate deficiency.Biomedical technologists can currently recognize abnormal leukocytes using human eyes. However, the quality and efficiency of diagnosis may be compromised due to the limitations of the biomedical technologists' eyesight, strength, and medical knowledge. Therefore, the development of an automatic leukocyte recognition system is feasible and necessary. It is essential to extract the leukocyte region from a blood smear image in order to develop an automatic leukocyte recognition system. The number of lobes increased when leukemia, chronic nephritis, liver disease, cancer, sepsis, and vitamin B12 or folate deficiency occurred. Clinical neutrophil hypersegmentation has been widely used as an indicator of B12 or folate deficiency.</p> <p>Results</p> <p>The purpose of this paper is to contribute an automatic leukocyte nuclei image segmentation method for such recognition technology. The other goal of this paper is to develop the method of counting the number of lobes in a cell nucleus. The experimental results demonstrated impressive segmentation accuracy.</p> <p>Conclusions</p> <p>Insensitive to the variance of images, the LNS (Leukocyte Nuclei Segmentation) method functioned well to isolate the leukocyte nuclei from a blood smear image with much better UR (Under Segmentation Rate), ER (Overall Error Rate), and RDE (Relative Distance Error). The presented LC (Lobe Counting) method is capable of splitting leukocyte nuclei into lobes. The experimental results illuminated that both methods can give expressive performances. In addition, three advanced image processing techniques were proposed as weighted Sobel operator, GDW (Gradient Direction Weight), and GBPD (Genetic-based Parameter Detector).</p

Signatures of afterglows from light dark matter boosted by supernova neutrinos in current and future large underground detectors

Supernova neutrino boosted dark matter (SN$\nu$ BDM) and its afterglow effect have been shown to be a promising signature for beyond Standard Model (bSM) physics. The time-evolution feature of SN$\nu$ BDM allows for possibly direct inference of DM mass $m_\chi$, and results in significant background suppression with improving sensitivity. This paper extends the earlier study and provides a general framework for computing the SN$\nu$ BDM fluxes for a supernova that occurs at any location in our galaxy. A bSM $U(1)_{L_\mu-L_\tau}$ model with its gauge boson coupling to both DM and the second and third generation of leptons is considered, which allows for both DM-$\nu$ and DM-$e$ interactions. Detailed analysis of the temporal profile, angular distribution, and energy spectrum of the SN$\nu$ BDM are performed. Unique signatures in SN$\nu$ BDM allowing extraction of $m_\chi$ and detail features that contain information of the underlying interaction type are discussed. Expected sensitivities on the above new physics model from Super-Kamiokande, Hyper-Kamiokande, and DUNE detections of BDM events induced by the next galactic SN are derived and compared with the existing bounds.Comment: 17 pages, 15 figures, 1 table, 5 appendice

Late onset of large benign ductus arteriosus aneurysm presented with increased nuchal translucency and cystic hygroma at first trimester Down syndrome screening

AbstractObjectiveFetal ductus arteriosus aneurysm (DAA) is a rare but potentially risky congenital heart disease. It is often not diagnosed until the third trimester because of its asymptomatic nature and late onset. In rare occasions, DAA may result in serious complications; therefore, prenatal diagnosis is helpful.Case ReportHerein, we report the case of a foetus with cystic hygroma and increased nuchal translucency in the first trimester (but regressed at 20-week anomalous scan). Karyotyping indicated a 46 XY genotype. A large vascular mass was noted at the apex of the left lung by Doppler ultrasound at 38 weeks of gestation, with a diameter of 12.5 mm. After birth, echocardiography showed a patent ductus arteriosus with aneurysmal dilatation (17 mm as the largest diameter); thus, DAA was impressed. Chest computed tomography and three-dimensional angiography confirmed the large aneurysmal dilatation of the ductus arteriosus with a closed end at the pulmonary arterial side.ConclusionThe male infant survived, but presented mild respiratory distress at birth. He was discharged at 24 days of age. At that time, DAA had regressed partially (diameter of 8.5 mm and much less blood flow), and it fully regressed at 40 days of age

Colonoscopy Screening Among US Adults Aged 40 or Older With a Family History of Colorectal Cancer

IntroductionColonoscopy screening reduces colorectal cancer (CRC) incidence and mortality. CRC screening is recommended at age 50 for average-risk people. Screening of first-degree relatives of CRC patients is recommended to begin at age 40 or 10 years before the age at diagnosis of the youngest relative diagnosed with CRC. CRC incidence has increased recently among younger Americans while it has declined among older Americans. The objective of this study was to determine whether first-degree relatives of CRC patients are being screened according to recommended guidelines. MethodsWe studied colonoscopy screening rates among the US population reporting a CRC family history using 2005 and 2010 National Health Interview Survey data. ResultsOf 26,064 study-eligible respondents, 2,470 reported a CRC family history; of those with a family history, 45.6% had a colonoscopy (25.2% in 2005 and 65.8% 2010). The colonoscopy rate among first-degree relatives aged 40 to 49 in 2010 (38.3%) was about half that of first-degree relatives aged 50 or older (69.7%). First-degree relatives were nearly twice as likely as nonfirst-degree relatives to have a colonoscopy (adjusted odds ratio [AOR], 1.7; 95% confidence interval, 1.5–1.9), but those aged 40 to 49 were less likely to have a colonoscopy than those in older age groups (AOR, 2.6 for age 50–64; AOR, 3.6 for age ≥65). Interactions with age, insurance, and race/ethnicity were not significant. Having health insurance tripled the likelihood of screening. ConclusionDespite a 5-fold increase in colonoscopy screening rates since 2005, rates among first-degree relatives younger than the conventional screening age have lagged. Screening promotion targeted to this group may halt the recent rising trend of CRC among younger Americans

Why Acute Ischemic Stroke Patients in the United States Use or Do Not Use Emergency Medical Services Transport? Findings of an Inpatient Survey

Background Patients with acute ischemic stroke (AIS) who use emergency medical services (EMS) receive quicker reperfusion treatment which, in turn, mitigates post-stroke disability. However, nationally only 59% use EMS. We examined why AIS patients use or do not use EMS. Methods During 2016–2018, a convenience sample of AIS patients admitted to a primary stroke center in South Carolina were surveyed during hospitalization if they were medically fit, available for survey when contacted, and consented to participate. The survey was programed into EpiInfo with skip patterns to minimize survey burden and self-administered on a touchscreen computer. Survey questions covered symptom characteristics, knowledge of stroke and EMS importance, subjective reactions, role of bystanders and financial factors. Descriptive and multiple regression analyses were performed. Results Of 108 inpatients surveyed (out of 1179 AIS admissions), 49% were male, 44% African American, mean age 63.5 years, 59% mild strokes, 75 (69%) arrived by EMS, 33% were unaware of any stroke symptom prior to stroke, and 75% were unaware of the importance of EMS use for good outcome. Significant factors that influenced EMS use decisions (identified by regression analysis adjusting for stroke severity) were: prior familiarity with stroke (self or family/friend with stroke) adjusted odds ratio, 5.0 (95% confidence interval, 1.6, 15.1), perceiving symptoms as relevant for self and indicating possible stroke, 26.3 (7.6, 91.1), and bystander discouragement to call 911, 0.1 (0.01,0.7). Further, all 27 patients who knew the importance of EMS had used EMS. All patients whose physician office advised actions other than calling EMS at symptom onset, did not use EMS. Conclusion Systematic stroke education of patients with stroke-relevant comorbidities and life-style risk factors, and public health educational programs may increase EMS use and mitigate post-stroke disability