1,081 research outputs found
The Classical Limit of Quantum Mechanics and the Fejer Sum of the Fourier Series Expansion of a Classical Quantity
In quantum mechanics, the expectation value of a quantity on a quantum state,
provided that the state itself gives in the classical limit a motion of a
particle in a definite path, in classical limit goes over to Fourier series
form of the classical quantity. In contrast to this widely accepted point of
view, a rigorous calculation shows that the expectation value on such a state
in classical limit exactly gives the Fej\'{e}r's arithmetic mean of the partial
sums of the Fourier series
The Motion Aftereffect: Mechanisms and Variants
The motion aftereffect causes a visual stimulus to undergo apparent motion. An adapting stimulus, which moves in a specific direction, adapts motion-responsive neurons in the middle temporal area (V5) to that direction of motion. Viewing a second stimulus, a test stimulus, produces apparent motion in the direction opposite that of the initial stimulus. Neural networks involved in attention and working memory are also implicated in the motion aftereffect. There is still little known regarding the mechanisms of the motion aftereffect, despite extensive documentation in the literature. This review discusses established knowledge of the motion aftereffect, focusing primarily on the middle temporal area. Variants of the motion aftereffect that are in line with the established mechanism with be discussed, namely the phantom motion aftereffect and sensory-contingent motion aftereffects, which incorporate color and visual surroundings into the production of the motion aftereffect. This optical illusion provides insight into motion processing as well as memory
Influences of Drosophila circadian clock on sugar-mediated physiological changes
It is widely known that high sugar consumption and poor sleep are detrimental to human health. Both are risk factors for obesity, which can lead to conditions such as heart disease. Despite this connection between sugar and sleep, little is known about how circadian clock dysfunction affects the physiological changes caused by increased sugar consumption. In this thesis, a mutant line of the model organism Drosophila melanogaster (ClkJrk, which contains a nonfunctional circadian rhythm gene known as Clk) that leads to circadian dysfunction, was exposed to a high sugar diet to observe how Clk affects sugar-related changes to food consumption, sleep, triglyceride levels, and starvation resistance. Despite previous research suggesting that the circadian rhythm affects feeding, ClkJrk flies did not substantially differ from wild-type flies in terms of food consumption. In addition, both ClkJrk and wild-type flies slept less on low-sugar food. However, unlike wild-type flies, ClkJrk flies did not experience increased starvation resistance on a high sugar diet, suggesting that a functioning Clk gene is essential for flies fed a high sugar diet to survive when starved. Lowered triglyceride levels in ClkJrk flies may explain the reduced starvation resistance of ClkJrk flies fed high sugar diets. The findings from this research provide a greater understanding of how sleep and sugar intertwine to affect health and disease. Future studies should explore the endocrine components of this relationship in Drosophila, particularly the Drosophila Insulin-Like Peptides (DILPs), which regulate nutrient storage and release
The Effects of Alcohol on the Developing Drosophila Nervous System
Ethanol is the most common human teratogen, contributing to fetal alcohol syndrome (FAS) when effects are the most severe. Key effects of fetal alcohol syndrome are observed in the nervous system. The high prevalence of prenatal alcohol exposure necessitates novel treatment and prevention methods. However, ethical issues prevent researching humans in utero. For this reason, the fruit fly Drosophila melanogaster has emerged as a model organism for studying FAS. Because Drosophila is a small and non-placental organism, its environment can be easily controlled, allowing for specific doses and time periods of ethanol exposure to be studied. This review discusses findings related to the impact of alcohol on the developing Drosophila nervous system. Findings related to reactive oxygen species (ROS) exposure, a consequence of prenatal alcohol exposure due to the metabolism of alcohol, are emphasized. Impacts of ethanol on insulin signaling and epidermal growth factors are also mentioned. Further research on Drosophila nervous system development under ethanol exposure may prove beneficial in the treatment and prevention of FAS
Inflammatory Mechanisms of Organ Crosstalk during Ischemic Acute Kidney Injury
Acute kidney injury (AKI) is a common complication during inpatient hospitalization, and clinical outcomes remain poor despite advancements in renal replacement therapy. AKI in the setting of multiple organ failure (MOF) remains a formidable challenge to clinicians and incurs an unacceptably high mortality rate. Kidney ischemia-reperfusion injury (IRI) incites a proinflammatory cascade and releases cellular and soluble mediators with systemic implications for remote organ injury. Evidence from preclinical models cites mechanisms of organ crosstalk during ischemic AKI including the expression of cellular adhesion molecules, lymphocyte trafficking, release of proinflammatory cytokines and chemokines, and modification of the host innate and adaptive immune response systems. In this paper, the influence of kidney IRI on systemic inflammation and distant organ injury will be examined. Recent experimental data and evolving concepts of organ crosstalk during ischemic AKI will also be discussed in detail
Long-term effectiveness of unboosted atazanavir plus abacavir/lamivudine in subjects with virological suppression: A prospective cohort study
Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant.We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (pVL), performing a time to loss of virological response (TLOVR 50 copies/mL.We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50 copies/mL. The third drug in the previous regimen was ritonavir-boosted atazanavir (ATV/r) in 79 (28%), and another ritonavir-boosted protease inhibitor (PI/r) in 29 (10%). Ninety (32%) had previously failed with a PI. Proportions of people with virological success at 48/96/144 weeks were 90%/87%/88% (TLOVR) and 74%/67%/59% (snapshot analysis), respectively. The rates of VF were 8%/8%/6%. Rates of adverse events leading to study discontinuation were 0.4%/1%/2%. The multivariable adjusted analysis showed an association between VF and nadir CD4+ (hazard ratio [HR] 0.63 [95% confidence interval [CI]: 0.42-0.93] per 100 cells higher), time with pVL ≤50 copies/mL (HR 0.87 [95% CI: 0.79-0.96] per 6 months longer), and previous failure with a PI (HR 2.78 [95% CI: 1.28-6.04]). Resistance selection at failure was uncommon.A switch to ATV + ABC/3TC in selected subjects with suppressed viremia was associated with low rates of VF and discontinuation due to adverse events, even in subjects not receiving ATV/r. The strategy might be considered in those with long-term suppression and no prior PI failure
Regional differences in AIDS and non-AIDS related mortality in HIV-positive individuals across Europe and Argentina: the EuroSIDA study
BACKGROUND
Differences in access to care and treatment have been reported in Eastern Europe, a region with one of the fastest growing HIV epidemics, compared to the rest of Europe. This analysis aimed to establish whether there are regional differences in the mortality rate of HIV-positive individuals across Europe, and Argentina.
METHODS
13,310 individuals under follow-up were included in the analysis. Poisson regression investigated factors associated with the risk of death.
FINDINGS
During 82,212 person years of follow-up (PYFU) 1,147 individuals died (mortality rate 14.0 per 1,000 PYFU (95% confidence interval [CI] 13.1-14.8). Significant differences between regions were seen in the rate of all-cause, AIDS and non-AIDS related mortality (global p<0.0001 for all three endpoints). Compared to South Europe, after adjusting for baseline demographics, laboratory measurements and treatment, a higher rate of AIDS related mortality was observed in East Europe (IRR 2.90, 95%CI 1.97-4.28, p<.0001), and a higher rate of non-AIDS related mortality in North Europe (IRR 1.51, 95%CI 1.24-1.82, p<.0001). The differences observed in North Europe decreased over calendar-time, in 2009-2011, the higher rate of non-AIDS related mortality was no longer significantly different to South Europe (IRR 1.07, 95%CI 0.66-1.75, p = 0.77). However, in 2009-2011, there remained a higher rate of AIDS-related mortality (IRR 2.41, 95%CI 1.11-5.25, p = 0.02) in East Europe compared to South Europe in adjusted analysis.
INTERPRETATIONS
There are significant differences in the rate of all-cause mortality among HIV-positive individuals across different regions of Europe and Argentina. Individuals in Eastern Europe had an increased risk of mortality from AIDS related causes and individuals in North Europe had the highest rate of non-AIDS related mortality. These findings are important for understanding and reviewing HIV treatment strategies and policies across the European region
Impact of metformin on feeding, behavior, and metabolism in Drosophila melanogaster.
Metformin is a first-line drug used in the treatment of type II diabetes mellitus and is the 4th-most prescribed drug in the United States. It functions in lowering blood glucose levels and increasing insulin sensitivity. Despite its wide scale use, the degree to which it affects aspects of behavior and metabolism unrelated to diabetes is not fully understood.
Recent studies have attempted to fill this gap, particularly in the context of metformin’s impact on lifespan. We decided to extend this research by focusing on measurable behaviors as well as traits related to metabolism and physiology. Using the fruit fly Drosophila melanogaster as a model organism, we investigated metformin’s impacts on food consumption, body weight, starvation resistance, and sleep. We observed preliminary evidence of increased feeding in Drosophila when given a metformin-supplemented diet. The same diet had an effect on body weight while making the flies less vulnerable to starvation stress. Metformin did not appear to have a significant impact on sleep patterns, except at low concentrations. These data show that metformin does cause multiple levels of side effects in the whole organism level.
Given that the molecular pathways of metformin action are conserved between Drosophila and humans, similar effects on food consumption and weight may be found in human subjects treated with metformin. Future study should include an analysis of the molecular, genetic, and neuronal mechanisms of the above physiological and metabolic changes
Involvement of mast cells in monocrotaline-induced pulmonary hypertension in rats
Background: Mast cells (MCs) are implicated in inflammation and tissue remodeling. Accumulation of lung MCs is described in pulmonary hypertension (PH); however, whether MC degranulation and c-kit, a tyrosine kinase receptor critically involved in MC biology, contribute to the pathogenesis and progression of PH has not been fully explored.Methods: Pulmonary MCs of idiopathic pulmonary arterial hypertension (IPAH) patients and monocrotaline-injected rats (MCT-rats) were examined by histochemistry and morphometry. Effects of the specific c-kit inhibitor PLX and MC stabilizer cromolyn sodium salt (CSS) were investigated in MCT-rats both by the preventive and therapeutic approaches. Hemodynamic and right ventricular hypertrophy measurements, pulmonary vascular morphometry and analysis of pulmonary MC localization/counts/activation were performed in animal model studies.Results: There was a prevalence of pulmonary MCs in IPAH patients and MCT-rats as compared to the donors and healthy rats, respectively. Notably, the perivascular MCs were increased and a majority of them were degranulated in lungs of IPAH patients and MCT-rats (p < 0.05 versus donor and control, respectively). In MCT-rats, the pharmacological inhibitions of MC degranulation and c-kit with CSS and PLX, respectively by a preventive approach (treatment from day 1 to 21 of MCT-injection) significantly attenuated right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH). Moreover, vascular remodeling, as evident from the significantly decreased muscularization and medial wall thickness of distal pulmonary vessels, was improved. However, treatments with CSS and PLX by a therapeutic approach (from day 21 to 35 of MCT-injection) neither improved hemodynamics and RVH nor vascular remodeling.Conclusions: The accumulation and activation of perivascular MCs in the lungs are the histopathological features present in clinical (IPAH patients) and experimental (MCT-rats) PH. Moreover, the accumulation and activation of MCs in the lungs contribute to the development of PH in MCT-rats. Our findings reveal an important pathophysiological insight into the role of MCs in the pathogenesis of PH in MCT- rats
Abnormal NK cell lymphocytosis detected after splenectomy: association with repeated infections, relapsing neutropenia, and persistent polyclonal B-cell proliferation
Abnormal NK cell lymphocytosis detected after splenectomy: association with repeated infections, relapsing neutropenia, and persistent polyclonal B-cell proliferation.
Granjo E, Lima M, Fraga M, Santos F, Magalhães C, Queirós ML, Moreira I, Rocha S, Silva AS, Rebelo I, Quintanilha A, Ribeiro ML, Candeias J, Orfão A.
Department of Hematology, Hospital S. João, Porto, Portugal. [email protected]
Abstract
We report the case of a boy with hereditary spherocytosis who presented with mild microcytic hypochromic anemia and recurrent leg ulcers that had been present since childhood. Chronic natural killer (NK) cell and B-cell lymphocytosis was detected 1 year after therapeutic splenectomy during investigation of recurrent episodes of neutropenia and persistent lymphocytosis. NK cells proved to be abnormal at immunophenotyping studies, and B-cells were polyclonal and displayed a normal immunophenotype. Genotypic analysis of T-cell receptor (TCR)-beta and TCR-gamma genes showed a germ-line pattern. The clinical course of this patient was characterized by multiple pulmonary infections and amygdalitis. We discuss the potential roles of persistent immune stimulation due to chronic hemolysis and severe leg ulcers and of splenectomy in the origin of NK cell lymphocytosis and the relationship between NK cells and recurrent infections, relapsing neutropenia, and polyclonal B-cell response
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