The “three-body problem,” the term coined for predicting the motion of three gravitating bodies in space, is essential for understanding a variety of astrophysical processes as well as a large class of mechanical problems, and has occupied some of the world’s best physicists, astronomers and mathematicians for over three centuries. Their attempts have led to the discovery of several important fields of science; yet its solution remained a mystery.
Category: Nevin Manimala
Adv Exp Med Biol. 2021;1256:191-200. doi: 10.1007/978-3-030-66014-7_7.
ABSTRACT
Age-related macular degeneration (AMD) is a multifactorial neurodegenerative disease, which is a leading cause of vision loss among the elderly in the developed countries. As one of the most successful examples of genome-wide association study (GWAS), a large number of genetic studies have been conducted to explore the genetic basis for AMD and its progression, of which over 30 loci were identified and confirmed. In this chapter, we review the recent development and findings of GWAS for AMD risk and progression. Then, we present emerging methods and models for predicting AMD development or its progression using large-scale genetic data. Finally, we discuss a set of novel statistical and analytical methods that were recently developed to tackle the challenges such as analyzing bilateral correlated eye-level outcomes that are subject to censoring with high-dimensional genetic data. Future directions for analytical studies of AMD genetics are also proposed.
PMID:33848002 | DOI:10.1007/978-3-030-66014-7_7
Int J Dermatol. 2021 Apr 13. doi: 10.1111/ijd.15586. Online ahead of print.
ABSTRACT
BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are potentially fatal adverse drug reactions. The characteristics of these diseases are changing with the use of novel drugs, posing new challenges to doctors. We aimed to review recent SJS/TEN cases in order to assist general practitioners with timely diagnosis and correct management.
METHODS: We conducted a retrospective chart review of SJS/TEN patients in a referral center in Taiwan from 2009 to 2019. We included 24 patients’ charts and analyzed demographic data, medication histories, clinical courses, human leukocyte antigen (HLA) alleles, and long-term complications.
RESULTS: The average age was 63.4 years, and the average toxic epidermal necrolysis-specific severity of illness score was 1.9. The most common culprit drug was carbamazepine (33.3%), followed by antibiotics (12.5%) and nonsteroidal anti-inflammatory drugs (8.3%). Two cases were caused by immune checkpoint inhibitors, and one of them had a long latency of 210 days. Three out of the four patients carrying HLA-B*15:02 had carbamazepine-induced SJS/TEN. All patients were treated with systemic corticosteroids in the acute stage of the diseases. The length of in-hospital stay did not correlate with the average daily dose of corticosteroids. The overall mortality rate was 4.2%, and the disease-specific mortality rate was 0%.
CONCLUSIONS: The most common culprit drug was carbamazepine, which had strong association with HLA-B*15:02. There was no statistically significant correlation between in-hospital stay and the average daily dose of corticosteroids. Immune checkpoint inhibitor-related SJS/TEN may have an extended latent period.
PMID:33848012 | DOI:10.1111/ijd.15586
J Magn Reson Imaging. 2021 Apr 13. doi: 10.1002/jmri.27639. Online ahead of print.
ABSTRACT
BACKGROUND: No data are available about normal ranges for native T1 in human myocardium using General Electric (GE) scanners.
PURPOSE: To establish normal ranges for myocardial T1 values and evaluate regional variability and the influence of physiological factors.
STUDY TYPE: Prospective.
SUBJECTS: One hundred healthy volunteers with normal electrocardiogram, no cardiovascular/systemic diseases, or risk factors (age range: 20-70 years; 50 females).
FIELD STRENGTH/SEQUENCE: 1.5 T/Steady-state free precession cine and a modified Look-Locker inversion recovery sequence in diastole (also in systole for 61 volunteers).
ASSESSMENT: Image analysis was performed by operators with >10 years experience in cardiac MR using commercially available software. T1 values were calculated for 16 myocardial segments, and the global value was the mean. Segments were grouped according to circumferential region (anterior, septal, inferior, and lateral) and to level (basal, medial, apical). Twenty images were analyzed twice by the same operator and by a different operator to assess reproducibility.
STATISTICAL TESTS: Independent-samples t-test or Mann-Whitney test; paired sample t-test or Wilcoxon signed-rank test; one-way repeated measures ANOVA or Friedman tests; Pearson’s or Spearman’s correlation. Reproducibility evaluated using coefficient of variability (CoV).
RESULTS: Due to artifacts and/or partial-volume effects, 45/1600 (2.8%) segments were excluded. A good intra- and inter-operator reproducibility was detected (CoV < 5%). There were significant differences in segmental T1 values (P < 0.05). A significant circumferential variability was present (P < 0.05): the mean native T1 value over the lateral region was significantly lower than in the other three regions. An increasing gradient from basal to apical slices was detected (P < 0.05). Segmental and global T1 values were not associated with age (range P = 0.052-0.911) but were significantly lower in males than in females (global: 993 ± 32 vs. 1037 ± 27 ms; P < 0.05) and significantly correlated with heart rate (range R for segmental values = 0.247-0.920; P < 0.05). Almost all segmental T1 values were inversely correlated with wall thickness (R from -0.233 to -0.514; P < 0.05). Systolic T1 values were significantly lower than diastolic values in basal anteroseptal segment, in all medial segments except the inferior one, and in all apical segments (P < 0.05).
DATA CONCLUSION: Myocardial T1 values differ among myocardial regions, are influenced by sex, heart rate, and wall thickness and vary according to the cardiac cycle in healthy adults.
LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.
PMID:33848021 | DOI:10.1002/jmri.27639
J Nephrol. 2021 Apr 13. doi: 10.1007/s40620-021-01020-2. Online ahead of print.
ABSTRACT
BACKGROUND: Growth Differentiation Factor-15 (GDF15) is a member of the TGF-β superfamily. Increased serum GDF15 has been associated with increased risk of chronic kidney disease (CKD) progression. However, no prior studies have addressed the significance of urinary GDF15 in adult CKD.
METHODS: We measured serum and urinary GDF15 in a prospective cohort of 84 patients who underwent kidney biopsy and assessed their association with outcomes (survival, kidney replacement therapy) during a follow-up of 29 ± 17 months.
RESULTS: There was a statistically significant correlation between serum and urine GDF15 values. However, while serum GDF15 values increased with decreasing glomerular filtration rate, urinary GDF15 did not. Immunohistochemistry located kidney GDF15 expression mainly in tubular cells, and kidney GDF15 staining correlated with urinary GDF15 values. Urine GDF15 was significantly higher in patients with a histologic diagnosis of diabetic nephropathy than in diabetic patients without diabetic nephropathy. This was not the case for serum GDF15. Both serum and urine GDF15 were negatively associated with patient survival in multivariate models. However, when both urine and serum GDF15 were present in the model, lower urine GDF15 predicted patient survival [B coefficient (SEM) – 0.395 (0.182) p 0.03], and higher urine GDF15 predicted a composite of mortality or kidney replacement therapy [0.191 (0.06) p 0.002], while serum GDF15 was not predictive. Decision tree analysis yielded similar results. The area under the curve (AUC) of the receiver operating curve (ROC) for urine GDF15 as a predictor of mortality was 0.95 (95% CI 0.89-1.00, p < 0.001).
CONCLUSIONS: In conclusion, urinary GDF15 is associated with kidney histology patterns, mortality and the need for renal replacement therapy (RRT) in CKD patients who underwent a kidney biopsy.
PMID:33847920 | DOI:10.1007/s40620-021-01020-2
Methods Mol Biol. 2021;2281:93-115. doi: 10.1007/978-1-0716-1290-3_6.
ABSTRACT
The ability of magnetic tweezers to apply forces and measure molecular displacements has resulted in its extensive use to study the activity of enzymes involved in various aspects of nucleic acid metabolism. These studies have led to the discovery of key aspects of protein-protein and protein-nucleic acid interaction, uncovering dynamic heterogeneities that are lost to ensemble averaging in bulk experiments. The versatility of magnetic tweezers lies in the possibility and ease of tracking multiple parallel single-molecule events to yield statistically relevant single-molecule data. Moreover, they allow tracking both fast millisecond dynamics and slow processes (spanning several hours). In this chapter, we present the protocols used to study the interaction between E. coli SSB, single-stranded DNA (ssDNA), and E. coli RecQ helicase using magnetic tweezers. In particular, we propose constant force and force modulation assays to investigate SSB binding to DNA, as well as to characterize various facets of RecQ helicase activity stimulation by SSB.
PMID:33847954 | DOI:10.1007/978-1-0716-1290-3_6
Methods Mol Biol. 2021;2307:221-232. doi: 10.1007/978-1-0716-1414-3_15.
ABSTRACT
Yarrowia lipolytica produces a range of valuable biotechnological products from natural metabolites and enzymes to heterologous proteins. The production of these products is affected by medium composition and various environmental factors. Here we describe bioprocess development for a recombinant laccase production by Y. lipolytica. At first, response surface methodology (RSM), as a statistical technique for design of experiment (DOE), is used for the optimization of medium composition in flask level. Then, results of RSM are applied to increase laccase production in controlled conditions of the bioreactor.
PMID:33847993 | DOI:10.1007/978-1-0716-1414-3_15
Indian J Pediatr. 2021 Apr 13. doi: 10.1007/s12098-021-03721-9. Online ahead of print.
ABSTRACT
Renal biopsy is an important diagnostic tool, though invasive and carries risks involved with sedation. The authors wanted to compare suspect histopathological diagnosis with final diagnosis and find out impact of biopsy findings on treatment. They retrospectively analyzed 108 patients. Details of patients, diagnosis, treatment and complications due to kidney biopsy were documented. Statistical analysis was done using SPSS version 20.0 (IBM, NY). Indications of 108 children (69 boys, 39 girls) undergoing renal biopsy were steroid-resistant nephrotic syndrome (35.1%), steroid-dependent nephrotic syndrome requiring calcineurin inhibitors (CNI) (12%), nephrotic range proteinuria with atypical features (16.7%), lupus nephritis (13%), and acute kidney injury (AKI) stage 3 (17.6%). Suspect and histopathological diagnoses were similar in 53% cases with agreement factor of 0.462. Treatment changed in 28.7%. Renal biopsy made substantial impact in patients with nephrotic range proteinuria with atypical features (55.6%) and AKI stage 3 (52.6%). One (0.9%) had developed gross hematuria, which resolved spontaneously.
PMID:33847911 | DOI:10.1007/s12098-021-03721-9
Dermatol Ther (Heidelb). 2021 Apr 13. doi: 10.1007/s13555-021-00522-y. Online ahead of print.
ABSTRACT
INTRODUCTION: Few studies have evaluated patient-reported outcome measures and the effect of patient educational materials in German patients with skin cancer. We conducted a prospective study to measure the impact of treatment on health-related quality of life in German patients with skin cancer, identify variables that may contribute to changes in health-related quality of life, and evaluate the effect of providing additional information through a patient education brochure.
METHODS: A total of 461 patients diagnosed with actinic keratosis, nonmetastatic nonmelanoma skin cancer, melanoma in situ, or nonmetastatic cutaneous melanoma treated between August 2018 and July 2020 were included. Ninety-seven patients were randomly selected to receive an additional patient education brochure (“Hautkrebs”). The patients completed a Skin Cancer Quality of Life Index Tool (n = 324) or a Skin Cancer Index Questionnaire (n = 137) 1 week after surgical treatment.
RESULTS: Ninety-seven patients were provided an additional patient education brochure. We found statistical correlation between sociodemographic factors (young age and female gender) and the location of the skin cancer (head and face) and impairment of health-related quality of life in patients with skin cancer (p < 0.05). Moreover, we found that patients who were presented a brochure showed significantly higher awareness concerning direct sun exposure (p < 0.05).
CONCLUSION: Impaired health-related quality of life is correlated with a patient with skin cancer’s age, gender, and the location of the lesion. Physicians should consider these factors in clinical practice and advocate the use of patient education brochures as effective assets in preventing the reoccurrence of skin cancer.
PMID:33847880 | DOI:10.1007/s13555-021-00522-y
Egypt Heart J. 2021 Apr 13;73(1):37. doi: 10.1186/s43044-021-00159-4.
ABSTRACT
BACKGROUND: Excess epicardial fat volume (EFV) has been recently implicated in cardiovascular structural and functional abnormalities. It has been associated with abnormal microvascular stiffness (as reflected by radial artery waveform; C2), which may result in microvascular dysfunction and contribute to the atypical chest pain syndrome without obstructive coronary artery disease (CAD). Women have been statistically shown to present with atypical chest pain more often than men and specifically without obstructive CAD. The aim of this study is to assess whether excess EFV in female subjects is associated with significant microvascular dysfunction (i.e., C2), in subjects without obstructive CAD.
RESULTS: We screened 596 asymptomatic subjects, ages 20-79, using the Early Cardiovascular Health Risk Scoring System (ECVHRS), which has been reported. Out of the 596 total subjects, 230 subjects had a CACS. Out of these 230 subjects, 77 subjects (45 females; 32 males) had a 0 CACS. The 45 females from this cohort were the subjects of this study, and they were further categorized into 3 groups: group 1 (normal EFV, non-obese female subjects; n=16), females with ECVHRS < 3 and ACC/AHA risk score < 5%; group 2 (n = 9), females with elevated EFV and no abdominal visceral obesity; and group 3 (n=20), females with elevated EFV and abdominal visceral obesity. The average EFV was determined to be 72±20 cm3 among group 1, which indicates the values for normal EFV. The results in group 2 indicate that excess EFV is contributing to the development of microvascular dysfunction, resulting in abnormal micro-arterial (C2) elasticity (p< 0.00001), increase in resting blood pressure (p =0.0001), an abnormal rise in blood pressure (BP) at rest and post-mild protocol exercise (PME) (p = < 0.00001), and abnormal increase in carotid intima-media thickness (CIMT) (p = 0.000164).
CONCLUSION: Excess EFV appears to be not only a novel cardiovascular risk marker, but also the culprit for other cardiovascular risk markers. Based on these findings, elevated EFV may contribute to the development of the atypical chest pain syndrome in females without obstructive CAD. Additionally, EFV is emerging as a potential clinically relevant significant cardiovascular risk biomarker and may become a target to reduce cardiovascular morbidity and mortality.
PMID:33847857 | DOI:10.1186/s43044-021-00159-4