Nanocelluloses (NC) increase mechanical and barrier paper properties allowing the use of paper in applications actually covered by other materials. Despite the exponential increase of information, NC ...have not been fully implemented in papermaking yet, due to the challenges of using NC. This paper provides a review of the main new findings and emerging possibilities in this field by focusing mainly on: (i) Decoupling the effects of NC on wet-end and paper properties by using synergies with retention aids, chemical modification, or filler preflocculation; (ii) challenges and solutions related to the incorporation of NC in the pulp suspension and its effects on barrier properties; and (iii) characterization needs of NC at an industrial scale. The paper also includes the market perspectives. It is concluded that to solve these challenges specific solutions are required for each paper product and process, being the wet-end optimization the key to decouple NC effects on drainage and paper properties. Furthermore, the effect of NC on recyclability must also be taken into account to reach a compromise solution. This review helps readers find upscale options for using NC in papermaking and identify further research needs within this field.
Metastasis is a major cause of morbidity and mortality in cancer patients. However, the molecular and cellular mechanisms underlying the ability of cancer cells to metastasize remain relatively ...poorly understood. Among all solid tumors, small cell lung cancer (SCLC) has remarkable metastatic proclivity, with a majority of patients diagnosed with metastatic disease. Our understanding of SCLC metastasis has been hampered for many years by the paucity of material from primary tumors and metastases, as well as the lack of faithful pre‐clinical models. Here, we review recent advances that are helping circumvent these limitations. These advances include methods that employ circulating tumor cells from the blood of SCLC patients and the development of diverse genetically engineered mouse models of metastatic SCLC. New insights into the cellular mechanisms of SCLC metastasis include observations of cell fate changes associated with increased metastatic ability. Ongoing studies on cell migration and organ tropism promise to expand our understanding of SCLC metastasis. Ultimately, a better molecular understanding of metastatic phenotypes may be translated into new therapeutic options to limit metastatic spread and treat metastatic SCLC.
Small cell lung cancer (SCLC) is highly metastatic, but rare resections of SCLC tumors and metastases have hampered our understanding of SCLC progression. This review offers a comprehensive overview of recent advances on models and mechanisms of SCLC metastasis.
Abstract Objective This work presents a system for a simultaneous non-invasive estimate of the blood glucose level (BGL) and the systolic (SBP) and diastolic (DBP) blood pressure, using a ...photoplethysmograph (PPG) and machine learning techniques. The method is independent of the person whose values are being measured and does not need calibration over time or subjects. Methodology The architecture of the system consists of a photoplethysmograph sensor, an activity detection module, a signal processing module that extracts features from the PPG waveform, and a machine learning algorithm that estimates the SBP, DBP and BGL values. The idea that underlies the system is that there is functional relationship between the shape of the PPG waveform and the blood pressure and glucose levels. Results As described in this paper we tested this method on 410 individuals without performing any personalized calibration. The results were computed after cross validation. The machine learning techniques tested were: ridge linear regression, a multilayer perceptron neural network, support vector machines and random forests. The best results were obtained with the random forest technique. In the case of blood pressure, the resulting coefficients of determination for reference vs. prediction were R SBP 2 = 0.91 , R DBP 2 = 0.89 , and R BGL 2 = 0.90 . For the glucose estimation, distribution of the points on a Clarke error grid placed 87.7% of points in zone A, 10.3% in zone B, and 1.9% in zone D. Blood pressure values complied with the grade B protocol of the British Hypertension society. Conclusion An effective system for estimate of blood glucose and blood pressure from a photoplethysmograph is presented. The main advantage of the system is that for clinical use it complies with the grade B protocol of the British Hypertension society for the blood pressure and only in 1.9% of the cases did not detect hypoglycemia or hyperglycemia.
Human alcohol-related neuropathology de la Monte, Suzanne M.; Kril, Jillian J.
Acta neuropathologica,
01/2014, Letnik:
127, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol ...(ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions.
Research in fear conditioning has provided a comprehensive picture of the neuronal circuit underlying the formation of fear memories. In contrast, our understanding of the retrieval of fear memories ...is much more limited. This disparity may stem from the fact that fear memories are not rigid, but reorganize over time. To bring some clarity and raise awareness about the time-dependent dynamics of retrieval circuits, we review current evidence on the neuronal circuitry participating in fear memory retrieval at both early and late time points following auditory fear conditioning. We focus on the temporal recruitment of the paraventricular nucleus of the thalamus (PVT) for the retrieval and maintenance of fear memories. Finally, we speculate as to why retrieval circuits change with time, and consider the functional strategy of recruiting structures not previously considered as part of the retrieval circuit.
New Findings
What is the central question of this study?
What are the determinants of muscle belly gearing, and how does it affect the torque rise?
What is the main finding and its importance?
Change ...in muscle thickness of the gastrocnemius medialis is related to variations in belly gearing. Belly gearing has a key role in the rise of muscle torque and rate of torque development (RTD). Besides, the increase of tendinous tissue stiffness could increase the torque rise as well, and in turn, the RTD. However, changes in the tendinous tissue stiffness showed no effects on muscle fascicle behaviour, suggesting a possible uncoupling between muscle and tendon mechanical properties.
During fixed‐end contractions, muscles bulge in thickness and/or width to maintain a constant volume, whereas tendons lengthen over the entire contraction period. These dynamic changes play a key functional role in modulating the generated torque. However, the literature has revealed a limited understanding of in vivo dynamic muscle–tendon changes during rapid contractions. Therefore, this study aimed to investigate the determinants of belly gearing (belly velocity/fascicle velocity) and its effects on rapid torque production during in vivo fixed‐end contractions. Twenty healthy males were recruited for the study. Muscle shape and tendon stiffness were manipulated by applying a transverse load (2–10 kg) and an ankle rotation manoeuvre, respectively. Ultrafast‐ultrasound was employed to quantify medial gastrocnemius architecture during evoked contraction and a dynamometer was used to measure the muscle torque and quantify the rate of torque development (RTD). Torque and RTD diminished by transverse load application, whereas they increased during the ankle rotation manoeuvre. Belly gearing declined with increasing transverse load but was unaffected by tendinous stiffness variations. Alterations in belly gearing were strongly related to variations in muscle thickness throughout any load applied and affected the torque rise rapidly. In contrast, changes in tendinous tissue stiffness affected the torque rise only but did not modify the muscle shape. These data may suggest that concurrent manipulation of the tendinous tissue stiffness and muscle shape does not affect the explosive rise in torque capacity, suggesting a possible uncoupling between mechanical properties of muscle and tendon.
Abstract Alzheimer׳s disease (AD) is the most common cause of dementia in North America. Growing evidence supports the concept that AD is a metabolic disease mediated by impairments in brain insulin ...responsiveness, glucose utilization, and energy metabolism, which lead to increased oxidative stress, inflammation, and worsening of insulin resistance. In addition, metabolic derangements directly contribute to the structural, functional, molecular, and biochemical abnormalities that characterize AD, including neuronal loss, synaptic disconnection, tau hyperphosphorylation, and amyloid-beta accumulation. Because the fundamental abnormalities in AD represent effects of brain insulin resistance and deficiency, and the molecular and biochemical consequences overlap with Type 1 and Type 2 diabetes, we suggest the term “Type 3 diabetes” to account for the underlying abnormalities associated with AD-type neurodegeneration. In light of the rapid increases in sporadic AD prevalence rates and vastly expanded use of nitrites and nitrates in foods and agricultural products over the past 30–40 years, the potential role of nitrosamine exposures as mediators of Type 3 diabetes is discussed.
Alzheimer's disease (AD) is the most common cause of dementia in North America. Growing evidence supports the concept that AD is fundamentally a metabolic disease that results in progressive ...impairment in the brain's capacity to utilize glucose and respond to insulin and insulin-like growth factor (IGF) stimulation. Moreover, the heterogeneous nature of AD is only partly explained by the brain's propensity to accumulate aberrantly processed, misfolded and aggregated oligomeric structural proteins, including amyloid-β peptides and hyperphosphorylated tau. Evidence suggests that other factors, including impaired energy metabolism, oxidative stress, neuroinflammation, insulin and IGF resistance, and insulin/IGF deficiency in the brain should be incorporated into an overarching hypothesis to develop more realistic diagnostic and therapeutic approaches to AD. In this review, the interrelationship between impaired insulin and IGF signalling and amyloid-β pathology is discussed along with potential therapeutic approaches. Impairments in brain insulin/IGF signalling lead to increased expression of amyloid-β precursor protein (AβPP) and accumulation of AβPP-Aβ. In addition, they promote oxidative stress and deficits in energy metabolism, leading to the activation of pro-AβPP-Aβ-mediated neurodegeneration cascades. Although brain insulin/IGF resistance and deficiency can be induced by primary or secondary disease processes, the soaring rates of peripheral insulin resistance associated with obesity, diabetes mellitus and metabolic syndrome quite likely play major roles in the current AD epidemic. Both clinical and experimental data have linked chronic hyperinsulinaemia to cognitive impairment and neurodegeneration with increased AβPP-Aβ accumulation/reduced clearance in the CNS. Correspondingly, both the restoration of insulin responsiveness and the use of insulin therapy can lead to improved cognitive performance, although with variable effects on brain AβPP-Aβ load. On the other hand, experimental evidence supports the concept that the toxic effects of AβPP-Aβ can promote insulin resistance. Together, these findings suggest that a positive feedback loop of progressive neurodegeneration can develop whereby insulin resistance drives AβPP-Aβ accumulation, and AβPP-Aβ fibril toxicity drives brain insulin resistance. This phenomenon could explain why measuring AβPP-Aβ levels in cerebrospinal fluid or imaging of the brain has proven to be inadequate as a stand-alone biomarker for diagnosing AD, and why the clinical trial results of anti-AβPP-Aβ monotherapy have been disappointing. Instead, the aggregate data suggest that brain insulin resistance and deficiency must also be therapeutically targeted to halt AD progression or reverse its natural course. The positive therapeutic effects of different treatments that address the role of brain insulin/IGF resistance and deficiency, including the use of intranasal insulin delivery, incretins and insulin sensitizer agents are discussed along with potential benefits of lifestyle changes to modify risk for developing mild cognitive impairment or AD. Altogether, the data strongly support the notion that we must shift toward the implementation of multimodal rather than unimodal diagnostic and therapeutic strategies for AD.
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