130 research outputs found
A Critical Review for the Possibility of Science without âEppue Si Muoveâ: From Thomas Kuhnâs Theory of Science to Psychology of Science
The theory of science that Thomas Kuhn built in the Structure of Scientific Revolutions was considered as a hypothetical framework in this study. Since the publication of the work, many questions have arisen that call for a psychology of science. These questions are moved to another dimension through the knowledge of the decision made within Galileo Affair, which occupies an important place in modern science, fundamentally arising from an epistemic struggle and emerging out of an unscientific base rather than the charge of unholiness. Abandoning the perspective which evaluates these questions within a historical process as a weak side of the Kuhnian theory of science, this study challenges the current approaches with an alternative approach. The epistemic complexity in the Kuhnian theory of science is an imperative complexity caused by human factors. From this perspective, there are potential questions for psychology of science as a field of study based on Kuhnian epistemology and it can be assumed that new problems may appear when the other epistemological questions which assumed as âansweredâ are reviewed in the scope of this study. The main thesis of this study is that psychology of science is possible as a valid and operationalizable research program based on Kuhnian theory of science
Biallelic and monoallelic variants in PLXNA1 are implicated in a novel neurodevelopmental disorder with variable cerebral and eye anomalies.
PURPOSE: To investigate the effect of PLXNA1 variants on the phenotype of patients with autosomal dominant and recessive inheritance patterns and to functionally characterize the zebrafish homologs plxna1a and plxna1b during development. METHODS: We assembled ten patients from seven families with biallelic or de novo PLXNA1 variants. We describe genotype-phenotype correlations, investigated the variants by structural modeling, and used Morpholino knockdown experiments in zebrafish to characterize the embryonic role of plxna1a and plxna1b. RESULTS: Shared phenotypic features among patients include global developmental delay (9/10), brain anomalies (6/10), and eye anomalies (7/10). Notably, seizures were predominantly reported in patients with monoallelic variants. Structural modeling of missense variants in PLXNA1 suggests distortion in the native protein. Our zebrafish studies enforce an embryonic role of plxna1a and plxna1b in the development of the central nervous system and the eye. CONCLUSION: We propose that different biallelic and monoallelic variants in PLXNA1 result in a novel neurodevelopmental syndrome mainly comprising developmental delay, brain, and eye anomalies. We hypothesize that biallelic variants in the extracellular Plexin-A1 domains lead to impaired dimerization or lack of receptor molecules, whereas monoallelic variants in the intracellular Plexin-A1 domains might impair downstream signaling through a dominant-negative effect
Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension
OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo
Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab
The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension
Association Between Urinary Angiotensinogen, Hypertension and Proteinuria In Pregnant Women with Preeclampsia
Introduction: Preeclampsia is a life-threatening disorder of pregnancy. The pathogenic mechanisms of preeclampsia remain uncertain. The aim of this study is to investigate the relation between urinary angiotensinogen (UAGT) levels, an indicator of local renin-angiotensin system (RAS) activity in the kidney, and blood pressure and urinary protein excretion in preeclampsia. Materials and methods: For this study, 90 women aged between 20-39 years were recruited. Spot urine samples were collected to measure urinary angiotensinogen/creatinine ratio (UAGT/UCre). Log(UAGT/UCre) was compared in pregnancies with and without preeclampsia and non-pregnant controls. Factors affecting log(UAGT/UCre) in pregnancies were also investigated. Results: In all pregnancies log(UAGT/UCre) levels were significantly higher than in non-pregnant controls (0.580.19 vs. 0.33 +/- 0.14, respectively, p=0.002). However, log(UAGT/UCre) levels in pregnancies with preeclampsia were slightly lower than in normal pregnancies (0.52 +/- 0.18 vs. 0.64 +/- 0.19, respectively, p=0.012). Log(UAGT/UCre) levels were correlated positively with blood pressure and proteinuria in pregnancies with preeclampsia. However, log(UAGT/UCre) levels were not correlated with age, height, body weight, gestational age, body mass index, and serum creatinine. Conclusion: This study showed that elevated local RAS activity in kidney was correlated with high blood pressure and proteinuria in preeclampsia. Local RAS activation in the kidneys may be one of the contributing factors in the development of preeclampsia.WoSScopu
Glomerular filtration rate and kidney size in type 2 hypertensive diabetic patients
Glomerular hyperfiltration is thought to play an important role in the genesis of diabetic nephropathy. While hyperfiltration is well documented in early Type 1 diabetes, the evidence for hyperfiltration in type 2 diabetes is conflicting. The aim of this study was to find out whether Type 2 hypertensive diabetic patients have hyperfiltration and renal hypertrophy and to asses the effects of an angiotensin converting enzyme (ACE) inhibitor, perindopril, on glomerular filtration rate (GFR), kidney size in hypertensive Type 2 diabetic patients. GFR and kidney size have been studied in 32 Type 2 hypertensive diabetic patients (M:F 16:16, mean age 40.9±1.2 year, mean duration of diabetes 2.6 ± 1.0 month) and 30 normal controls (M:F 15:15, mean age 40. 3 .± 2.5) enrolled into this study. In normal subjects total GFR, right and left kidney sizes (length à width) were 105.3 ± 7.0 ml/min, 101.4±2.3 mm à 55.7±3.8 mm and 102.8±2.1 mm à 52.0 ± 4.2 mm. In diabetic patients total GFR, right and left kidney sizes (length width) were 100.6 ± 7.1 ml/min (p> 0.05), 99.12 ± 1.5 mm à 50.03 ± 1.08 mm (p >0.05) and 101.0 ± 1.4 mm à 47.53 ± 1.2 mm (p>0.05) respectively. Patients were prescribed perindopril for eight months. After perindopril treatment, GFR and kidney size did not change significantly. In conclusion there was no hyperfiltration and renal hypertrophy in Type 2 hypertensive diabetic patients. The lack of glomerular hypertrophy, nephromegaly and hyperfiltration suggests that diabetic glomerulopathy is not always associated with preceding hyperfiltration. As a result of this, perindopril therapy did not change kidney size and glomerular filtration rate
- âŠ