Damage Hypothesis Research Articles

A novel neuroprotective method against ischemic stroke by accelerating the drainage of brain interstitial fluid.

Ischemic stroke is a leading cause of death and disability worldwide. Inflammatory response after stroke determines the outcome of ischemic injury. A recent study has reported an efficient method, epidural arterial implantation (EAI), for accelerating interstitial fluid (ISF) drainage, which provides a promising strategy to clear pro-inflammatory cytokines in the brain extracellular space (ECS). In this study, the method of EAI was modified (m-EAI) to control its function of accelerating the ISF drainage at different time points following ischemic attack. The neuroprotective effect of m-EAI on ischemic stroke was evaluated with the transient middle cerebral artery occlusion (tMCAO) rat model. The results demonstrated the accumulation of IL-1β, IL-6, and TNF-α was significantly decreased by activating m-EAI at 7 d before and immediately after ischemic attack in tMCAO rats, accompanied with decreased infarct volume and improved neurological function. This study consolidates the hypothesis of exacerbated ischemic damage by inflammatory response and provides a new perspective to treat encephalopathy via brain ECS. Further research is essential to investigate whether m-EAI combined with neuroprotective drugs could enhance the therapeutic effect on ischemic stroke.

Fatigue Analysis of Composite Bolted Joints under Random and Constant Amplitude Fatigue Loadings.

This paper attempts to analyze the random fatigue life and failure modes of joints using two calculation methods. Three kinds of tests were carried out, which were the static test, constant amplitude fatigue test and the random fatigue test, and four kinds of joints were designed. After the static test, the joint was subjected to a constant amplitude fatigue test by selecting different percentages of load according to the static strength. In order to predict the random fatigue life more precisely, two calculation methods were carried out, which were the linear cumulative damage method and the equivalent loading finite element method. Based on the linear cumulative damage hypothesis, the fatigue life of the joint was established as a function of the load amplitude, and then, the random life prediction was calculated by the amplitude distribution of the random loading. Another method was the equivalent loading method, which was to obtain the equivalent constant amplitude fatigue loading of the random loading spectrum. The finite element model was established based on the stiffness and strength degradation rule. The equivalent random life and fatigue failure modes of the joint were modeled. The two life prediction methods show good agreement with the fatigue experimental result, and all prediction results were included in a scatter band of the factor of 2.

Mechanisms of Pulmonary Vasculopathy in Acute and Long-Term COVID-19: A Review.

Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of its pathogenesis, highlighting the fact that there is a specific pulmonary vascular disorder. Indeed, COVID-19 may predispose patients to thrombotic disease in both venous and arterial circulation, and many cases of severe acute pulmonary embolism have been reported. The demonstrated presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the endothelial cells suggests that direct viral effects, in addition to indirect effects of perivascular inflammation and coagulopathy, may contribute to pulmonary vasculopathy in COVID-19. In this review, we discuss the pathological mechanisms leading to pulmonary vascular damage during acute infection, which appear to be mainly related to thromboembolic events, an impaired coagulation cascade, micro- and macrovascular thrombosis, endotheliitis and hypoxic pulmonary vasoconstriction. As many patients develop post-COVID symptoms, including dyspnea, we also discuss the hypothesis of pulmonary vascular damage and pulmonary hypertension as a sequela of the infection, which may be involved in the pathophysiology of long COVID.

Online stress and offline stress: Uniqueness, differences, and cumulative effect on multiple well-being outcomes

There is an increasing interaction between our offline and online lives, which puts forward a challenge to understanding the relationship between stress and health, as online and offline stress may be mixed. This study used 4,127 adolescents to test the uniqueness of online stress, the distinction between online and offline stress, and their co-occurrence and cumulative effects. The results showed that after controlling for offline stress, online stress still contributed to multiple well-being outcomes. Correspondence analysis revealed that online stress was more similar to daily hassles/perceived stress (global stress) compared to major life events. Latent profile analysis (LPA) revealed that adolescents who experienced certain levels of offline stress also experienced similar levels of online stress, indicating that they co-occur. Besides, the predictions of online and the three types of offline stress are consistent with the cumulative damage hypothesis of stress. Its theoretical and practical implications are discussed.

Comparing linear damage hypothesis to linear elastic fracture mechanics in the estimation of fatigue life in a high speed light craft

Linear elastic fracture mechanics methods provide a more comprehensive representation of crack propagation compared to traditional methods such as the linear damage hypothesis (or SN curve approach). These techniques have been widely adopted in the aerospace industry, however, their usage in the design of marine structures remains limited. The presented research uses full-scale trial data measured onboard a 111 m wave-piercing catamaran to compare the results obtained from linear elastic fracture mechanics and SN curve-based methods. The results reveal significant differences in estimated fatigue life between SN curve-based methods and fracture mechanics methods. These differences are likely due to limitations in the fracture mechanics model during the crack initiation phase. Changes in fracture mechanics parameters also had a significant effect on fatigue life, suggesting that if accuracy is important then material specific parameters are required. Despite the limitations shown, linear elastic fracture mechanics methods have a higher level of tailor-ability when compared to SN curve based methods and could offer benefits in situations such as the tracking of known flaws or in the assessment of changes to vessel configuration, or usage profiles.

Understanding Intervertebral Disc Degeneration: Background Factors and the Role of Initial Injury.

The etiology of intervertebral disc degeneration (IVDD) is complex and multifactorial, and it is still not fully understood. A better understanding of the pathogenesis of IVDD will help to improve treatment regimens and avoid unnecessary surgical aggression. In order to summarize recent research data on IVDD pathogenesis, including genetic and immune factors, a literature review was conducted. The pathogenesis of IVDD is a complex multifactorial process without an evident starting point. There are extensive data on the role of the different genetic factors affecting the course of the disease, such as mutations in structural proteins and enzymes involved in the immune response. However, these factors alone are not sufficient for the development of the disease. Nevertheless, like mechanical damage, they can also be considered risk factors for IVDD. In conclusion, currently, there is no consensus on a single concept for the pathogenesis of IVDD. We consider the intervertebral disc autoimmune damage hypothesis to be the most promising hypothesis for clinicians, because it can be extrapolated to all populations and does not counteract other factors. The genetic factors currently known do not allow for building effective predictive models; however, they can be used to stratify the risks of individual populations.

Temporal Changes in Functional and Structural Neuronal Activities in Auditory System in Non-Severe Blast-Induced Tinnitus.

Background and Objectives: Epidemiological data indicate that blast exposure is the most common morbidity responsible for mild TBI among Service Members (SMs) during recent military operations. Blast-induced tinnitus is a comorbidity frequently reported by veterans, and despite its wide prevalence, it is also one of the least understood. Tinnitus arising from blast exposure is usually associated with direct structural damage that results in a conductive and sensorineural impairment in the auditory system. Tinnitus is also believed to be initiated by abnormal neuronal activities and temporal changes in neuroplasticity. Clinically, it is observed that tinnitus is frequently accompanied by sleep disruption as well as increased anxiety. In this study, we elucidated some of the mechanistic aspects of sensorineural injury caused by exposure to both shock waves and impulsive noise. The isolated conductive auditory damage hypothesis was minimized by employing an animal model wherein both ears were protected. Materials and Methods: After the exposure, the animals' hearing circuitry status was evaluated via acoustic startle response (ASR) to distinguish between hearing loss and tinnitus. We also compared the blast-induced tinnitus against the well-established sodium salicylate-induced tinnitus model as the positive control. The state of the sensorineural auditory system was evaluated by auditory brainstem response (ABR), and this test helped examine the neuronal circuits between the cochlea and inferior colliculus. We then further evaluated the role of the excitatory and inhibitory neurotransmitter receptors and neuronal synapses in the auditory cortex (AC) injury after blast exposure. Results: We observed sustained elevated ABR thresholds in animals exposed to blast shock waves, while only transient ABR threshold shifts were observed in the impulsive noise group solely at the acute time point. These changes were in concert with the increased expression of ribbon synapses, which is suggestive of neuroinflammation and cellular energy metabolic disorder. It was also found that the onset of tinnitus was accompanied by anxiety, depression-like symptoms, and altered sleep patterns. By comparing the effects of shock wave exposure and impulsive noise exposure, we unveiled that the shock wave exerted more significant effects on tinnitus induction and sensorineural impairments when compared to impulsive noise. Conclusions: In this study, we systematically studied the auditory system structural and functional changes after blast injury, providing more significant insights into the pathophysiology of blast-induced tinnitus.

COVID-19 and the possible development of autoimmune thyroid diseases

In the midst of continuing coronavirus infection (COVID-19) there has been an increase in the incidence of various autoimmune pathologies. Particular attention to the potential relationship between coronavirus infection and autoimmune diseases is attracted by the positive therapeutic effect of the treatment of severe forms of COVID-19 with drugs used in the treatment of rheumatologically diseases.The results of the study should be the starting point for understanding the mechanisms of possible breakdown of immunological tolerance and the development of autoimmune thyroid diseases.AIM: To assess the risks of developing autoimmune thyroid disease after COVID-19, and to investigate the effect of therapy in the acute period on the possible development of autoimmune thyroid diseases.MATERIALS AND METHODS: This prospective comparative study included patients hospitalized at the National Medical Research Center for Endocrinology with a clinical and laboratory analysis of COVID-19 and bilateral polysegmental viral pneumonia (n=41). Patients with COVID-19 were divided into two subgroups: a subgroup of patients who received tocilizumab therapy in acute period (n=10), the second subgroup of patients who received symptomatic therapy during the acute period COVID-19 (n=31).To assess the functional status of the thyroid gland all patients underwent observation of the thyroid-stimulating hormone (TSH), free triiodothyronine (T3f), free thyroxine (T4f), antibodies to thyroperoxidase (Ab-TPO) and antibodies to the TSH receptor (Ab-recTSH).The concentrations of 27 signaling molecules in the blood serum were assessed by the technology of multiplex flow immunoassay using the Bio-Plex Pro Human Cytokine 27-plex Assay kit of cytokines and chemokines: interleukins-1b, -1ra, -2, 4-10, -12, -13, -15, -17 (IL-1b, IL-1ra, IL-2, IL - 4-10, IL-12, IL-13, IL-15, IL-17), Eotaxin, fibroblast growth factor (FGF), granulocyte- macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G -CSF), interferon-gamma (IFN-g), IFNγ-inducible protein 10 (IP-10), monocyte chemotactic protein-1 (MCP-1), also known as monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein -1 (MIP-1a and -1b), platelet growth factor BB (PDGF-bb), Regulated on Activation Normal T-cell Expressed and Secreted (RANTES), tumor necrosis factor-alpha (TNF-a), vascular endothelial growth factor (VEGF).All patients denied the presence of thyroid diseases, palpation of the thyroid gland revealed nodular formations in 5% of patients, and appropriate recommendations were given to patients.RESULTS: The overt hypothyroidism was detected in 2.4% of patients, subclinical - in 7.3% of patients in six months after the onset of coronavirus infection, and also found increased levels of the Ab-TPO in six months after recovery (p = 0.023 - Wilcoxon test). In the group of patients with increased Ab-TPO levels after COVID-19, statistically significantly high levels of IFN-g (p = 0.007), Eotaxin (p = 0.008) were obtained. An increased Ab-recTSH were revealed in the group of patients with severe COVID-19 who did not receive pathogenetic therapy with tocilizumab in the acute period (p = 0.046 - Mann-Whitney test).CONCLUSION: The results of our study and the scientific work of foreign colleagues demonstrate the potential risks of developing autoimmune thyroid diseases after a coronavirus infection. A close relationship was found between changes in the thyroid profile and hyperactivation of the immune system with hyperproduction of pro-inflammatory interleukins in COVID-19. This statement is confirmed by the revealed overt and subclinical hypothyroidism, as well as an increase in Ab- TPO levels in this group of patients after a coronavirus infection (p = 0.023 - Wilcoxon test) with a simultaneous persistent increased levels of some pro-inflammatory cytokines in dynamics, determined by autoimmune thyroiditis.The hypothesis of thyroid tissue damage by pro-inflammatory cytokines during COVID-19, as well as the hypothesis suggesting a protective effect on the development of autoimmune thyroid diseases by therapy with tocilizumab in the acute period were confirmed by increased levels of Ab-recTSH in patients with severe COVID-19 who did not receive tocilizumab in the acute period (p = 0.046 - Mann-Whitney test).

Is S100B Involved in Attention-Deficit/Hyperactivity Disorder (ADHD)? Comparisons with Controls and Changes Following a Triple Therapy Containing Methylphenidate, Melatonin and ω-3 PUFAs.

Increasing evidence supports a neuroinflammatory basis in ADHD damaging glial function and thereby altering dopaminergic (DA) neurotransmission. Previous studies focusing on the S100B protein as a marker of glial function have shown contradictory results. We conducted a clinical trial to investigate differences in S100B levels between ADHD patients and controls, as well as observe gradual changes in S100B concentrations after a triple therapy (TT) containing methylphenidate (MPH), melatonin (aMT) and omega-3 fatty acids (ω-3 PUFAs). 62 medication-naïve children with ADHD (ADHD-G) and 65 healthy controls (C-G) were recruited. Serum S100B was measured at baseline (T0) in ADHD-G/C-G, and three (T3) and six months (T6) after starting TT in the ADHD-G, together with attention scores. A significant increase in S100B was observed in the ADHD-G vs. C-G. In the ADHD-G, significantly higher S100B values were observed for comparisons between T0-T3 and between T0-T6, accompanied by a significant improvement in attention scores for the same timepoint comparisons. No significant differences were found for S100B between T3-T6. Our results agree with the hypothesis of glial damage in ADHD. Further studies on the link between DA and S100B are required to explain the transient increase in S100B following TT.

Multimodality strategy for cardiac damage assessment in falciparum malaria: A preliminary study

Malaria caused by the Plasmodium falciparum (P.f) parasite can result in life-threatening complications. Traditionally, cardiac involvement has not been included as a frequent cause of morbidity and mortality. Cardiac damage in P.f infection is probably underdiagnosed. To analyze the hypothesis of cardiac damage in apparently uncomplicated P.f infection with a multimodality strategy unavailable in most endemic countries. Cardiac biomarkers, ECG and 24 h ECG recording, transthoracic echocardiography with global strain analysis, and complete CMR analysis, including T2 (Fig. 1) and T1 mapping and extracellular volume quantification (ECV), were performed in patients hospitalized for malaria in a French tertiary center. Ten cases (sex ratio: 1 – mean age: 45 ± 13 years) imported from sub-Saharan Africa were prospectively included. Mean P.f parasitemia was 1.6 ± 1.7%. Hs-c Troponin T and NT pro BNP were mildly increased respectively in 1 and 2 patients. 24-h ECG recording revealed > 500 ventricular premature beats in 2 patients. Imaging revealed normal left and right ventricular systolic function, diastolic function and longitudinal global strain in all but one patient. CMR revealed 2 cases of focal late gadolinium enhancement consistent with the diagnosis of acute myocarditis in 1 case. ECV value was increased in 1 case (dilated cardiomyopathy). All patients were treated with piperaquine + dihydroartemisine and had a favorable outcome. Multimodality strategy reveals some cardiac abnormalities (ventricular ectopy, myocarditis) in patients hospitalized for falciparum malaria. Specificity of such findings remains questionable in this preliminary study. Further investigation is required to conclude about the hypothesis of a significant malaria-induced cardiac.

Collateral damage from debunking mRNA vaccine misinformation.

Amid the COVID-19 pandemic, the scientific community has been understandably eager to combat misinformation about issues such as vaccine safety. In highly polarized information environments, however, even well-intentioned messages have the potential to produce adverse effects. In this study, we connect different disciplinary strands of social science to derive and experimentally test the novel hypothesis that although particular efforts to debunk misinformation about mRNA vaccines will reduce relevant misperceptions about that technology, these correctives will harm attitudes toward other types of vaccines. We refer to this as the "collateral damage hypothesis." Our study specifically examines a corrective message stating that "mRNA vaccines do not contain live virus," and our results offer some support for our hypothesis, with the corrective triggering increased societal risk perceptions of live vaccines. We also find that the effect is, predictably, most evident among those whose vaccine acceptance is low. Building on the theoretical grounding we outline, we test a "damage control" adjustment to the corrective message and present evidence supporting that it mitigates the collateral damage.

PSAT235 The Role of Systemic Immune Activation in the Development of Thyroid Dysfunction in COVID-19

Abstract Background The research of cytokine-induced thyropathies in the midst of continuing COVID-19 pandemic is a very important and urgent problem. This work is based on the hypothesis that the hyperactivation of the immune system during COVID-19 is accompanied by a massive production of proinflammatory cytokines, and this could lead to thyroid gland disruption. Aim The primary endpoint is to assess the relationship between the levels of thyroid-stimulating hormone (TSH), free triiodothyronine (T3f), and free thyroxine (T4f) with the inflammatory process markers. The secondary endpoint is the identification of an association between TSH, T3f, T4f values, and patient survival. Materials and Methods This retrospective, single-center study included 122 patients hospitalized at the National Endocrinology Research Centre with a clinical and laboratory analysis of COVID-19 and bilateral polysegmental viral pneumonia. To assess the functional status of the thyroid gland all patients underwent observation of the TSH, T3f, T4f, AT-TPO, and AT-recTSH. Additionally, the markers of the inflammatory process were assessed in all patients, including: interleukin-6 (IL-6). Results Five patients (4%) were found with subclinical thyrotoxicosis. Serum TSH values were inversely correlated with IL-6 (r: -0.221; p = 0.024). Analysis of the level of hospital mortality, stratified by TSH, revealed statistically significantly lower TSH values in the group of deceased patients (p = 0.012). The median TSH in surviving patients was 1.34 [0.85; 1.80], for the deceased 0.44 [0.29; 0.99]. Based on the hypothesis that the immunosuppressive effect of genetically engineered biological therapy may have a protective role against thyroid damage in the development of cytokine storm, a comparative analysis of TSH values in two groups of patients with cytokine storm was performed (p=0.080). Conclusion Our research shows that the trigger of thyropathies in coronavirus infection is most likely thyroid tissue damage by the proinflammatory cytokines. In addition to the pathophysiological aspects of thyrotoxicosis, this study shows some specific clinical aspects regarding the clinical relevance in patients with thyrotoxicosis and COVID-19, namely, the high hospital mortality rate. The results obtained indicate a high risk of developing cytokine-induced thyropathies in patients with COVID-19. In support of the hypothesis of thyroid tissue damage being caused by pro-inflammatory cytokines, the differences in detected TSH values rose to the level of a statistical trend in 2 groups of patients with cytokine storm (i.e., patients who received tocilizumab therapy, and patients who received symptomatic therapy). Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Differential expression patterns of genes associated with metabolisms, muscle growth and repair in Pectoralis major muscles of fast- and medium-growing chickens.

The aim of this study was to investigate the expression of genes related to muscle growth, hypoxia and oxidative stress responses, a multi-substrate serine/threonine-protein kinase (AMPK) and AMPK-related kinases, carbohydrate metabolism, satellite cells activities and fibro- adipogenic progenitors (FAPs) in fast-growing (FG) (n = 30) and medium-growing (MG) chickens (n = 30). Pectoralis major muscles were collected at 7d, 14d, 21d, 28d, 35d and 42d of age. According to their macroscopic features, the samples from FG up to 21d of age were classified as unaffected, while all samples collected at an older age exhibited macroscopic features ascribable to white striping and/or wooden breast abnormalities. In contrast, MG samples did not show any feature associated to muscle disorders. The absolute transcript abundance of 33 target genes was examined by droplet digital polymerase chain reaction. The results showed differential gene expression profiles between FG and MG chickens at different ages. While most genes remained unchanged in MG chickens, the expression patterns of several genes in FG were significantly affected by age. Genes encoding alpha 1, alpha 2, beta 2 and gamma 3 isoforms of AMPK, as well as AMPK-related kinases, were identified as differentially expressed between the two strains. The results support the hypothesis of oxidative stress-induced muscle damage with metabolic alterations in FG chickens. An increased expression of ANXA2, DES, LITAF, MMP14, MYF5 and TGFB1 was observed in FG strain. The results suggest the occurrence of dysregulation of FAP proliferation and differentiation occurring during muscle repair. FAPs could play an important role in defining the proliferation of connective tissue (fibrosis) and deposition of intermuscular adipose tissue which represents distinctive traits of muscle abnormalities. Overall, these findings demonstrate that dysregulated molecular processes associated with myopathic lesions in chickens are strongly influenced by growth rate, and, to some extent, by age.

Do hiatal expansion and levator avulsion have a role in causation of pelvic organ prolapse?

AimTo examine whether hiatal expansion and levator avulsion have a role in the causation of pelvic organ prolapse (POP). MethodsData from studies which showed a strong association of hiatal expansion and levator avulsion were analysed for causation against an alternative view, POPcausation by ligament/connective tissue damage. ResultsSome studies potentially fitted the “Regularity Theory of Causality”; i.e., an apparent cause, occurred with such regularity as to be considered a cause. However, these studies failed the logical requirement of “unconditional”: all levator avulsions were to be followed directly by occurrence of POP, if the association were to be considered valid.Two studies which placed a large mesh behind the rectum and around puborectalis muscle greatly diminished levator expansion, but POP recurred in 78% of the women by 12 months. These results invalidated hypotheses of cause (levator expansion) and effect (prolapse). ConclusionsLevator avulsion/hiatal expansion co-occurs with POP. The cause for both is likely inability of the birth canal to plasticize” sufficiently to prevent simultaneous damage to the hiatal muscles and surrounding fascias and ligaments, which explains the co-occurrence. Greater than 90% cure of POP by site-specific repair of up to 4 pelvic ligaments supported the alternative hypothesis of simultaneous damage to pelvic ligaments to cause prolapse.

Effects of prenatal testosterone on cumulative markers of oxidative damage to organs of young adult zebra finches (Taeniopygia guttata).

We tested the hypothesis that exposure of avian embryos to androgens in ovo entails long-term costs in the form of oxidative damage to vital cells and organs in adulthood. We injected zebra finch eggs with testosterone (T), monitored postnatal growth, and analyzed markers of oxidative damage in heart and liver in mature birds. We measured 8-oxo-2'-deoxyguanosine and isoprostanes, markers of oxidative damage to DNA and membrane lipids, respectively. T treatment (1) reduced growth rates of female but not male nestlings vs. controls; (2) resulted in less accumulation of 8-oxo-dG, but not IsoPs, in liver tissue of 60-day-old females, but not males; and (3) a trend toward elevated 8-oxo-dG levels in heart tissue of males and females at 60 and 180days old combined. These results generally support the testosterone oxidative damage hypothesis, in that embryonic exposure to higher T resulted in damage to DNA of heart tissue in both sexes. They also suggest that sex-specific effects of androgens on early growth rates may carry over as differences in some forms of oxidative damage in adults. This supports a basic tenet of evolutionary aging theory that developmental influences early in life can be linked to costs later on.

Analysis of Longitudinal Beam Damage of a Container Chassis Semi-Trailer Using Finite Element Method – Case Study

This study investigates the damage of a container chassis loaded with a container having a capacity of 22 thousand litres. The chassis was damaged during full-load operation. Based on the observed effects of damage induced in a longitudinal beam (longeron) of the container chassis, a hypothetical course of events was elaborated. An attempt was made to recreate the actual course of events by eliminating the reasons due to which the effects of damage significantly differed from those observed post factums. To this end, numerical finite element method (FEM) simulations were performed using the Abaqus software. The damaged longitudinal beam of the container chassis was modelled using three-dimensional (3D) solid elements. It was assumed that the beam had the same profile cross-section over its entire length. In the numerical model, the container chassis had a pinned support on the fifth wheel. Elastic elements were used to model the axle-supported regions of the container chassis with the wheels. The following three events were identified as the potential causes of container chassis damage: the container chassis was supported by the bumper on the ground when the wheels on the right side were in contact with the bottom of the road surface cavity; the container chassis was supported by the bumper on the ground when the wheels on the right side were not in contact with the bottom of the road surface cavity; the bumper was subjected to point impact during vehicle reversal. The numerical results demonstrated that for each of the proposed damage hypothesis, the highest reduced stresses were located in the very region where the container chassis damage was actually observed. It was found that the observed damage was most probably induced when the container chassis was supported on the bumper and there was no contact between the wheels and the road surface due to the presence of a cavity in the road surface. Moreover, analytical calculation results demonstrated that the force acting on the structural members of the container chassis in the analysed load case exceeded the force resulting from the static load of the structure by more than 2.5 times. The load-induced stress in the beam material significantly exceeded the strength of the structure.

Volume changes of thalamus, hippocampus and cerebellum are associated with specific CSF profile in MS

Background: The underlying pathogenesis of surface-in grey matter abnormalities in MS, demonstrated by both neuropathology and advanced MRI analyses, is under investigation and it might be related to CSF-mediated mechanism of inflammation and/or damage. Objective: To examine the link of CSF inflammatory profile with the damage of three regions early-involved in MS and bordering with CSF: thalamus, hippocampus and cerebellum. Methods: In this longitudinal, prospective study, we evaluated, in 109 relapsing–remitting MS patients, at diagnosis and after 2-year follow-up, the association between the baseline CSF level of 19 inflammatory mediators and the volume changes of thalamus, hippocampus, cerebellar cortex and control regions (globus pallidus, putamen). Results: The multivariable analysis showed that the CXCL13 and sCD163 CSF levels at baseline were independent predictors of thalamus (; p < 0.001) and hippocampus (; p < 0.001) volume change after 2-year follow-up. These molecules, plus CCL25, IFN-γ and fibrinogen, were independent predictors of the cerebellar cortex volume loss (; p < 0.001). No independent predictors of volume changes of the control regions were found. Conclusion: Our results indicate an association between the CSF inflammatory profile and grey matter volume loss of regions anatomically close to CSF boundaries, thus supporting the hypothesis of a surface-in GM damage in MS.

The Hypothesis of Unexplained Brain Damage and Learning Difficulties

Introduction: The term learning disabilities refers to a complex and multidimensional phenomenon that affects many thousands of students. Due to the rich symptomatology of learning difficulties and the increased differences between individuals, it has not been possible to analyze all cases exclusively from the perspective of the neuropsychological approach. Aim. The aim of this study was to present research conducted in the context of theories on the brain function of people with learning disabilities. Supporting the hypothesis of brain dysfunction. Methodology: Literature review was carried out in the web, which referred to researches on Special Learning Disabilities and the brain function associated with them. Results: Review of the literature highlighted key points of the relationship between learning difficulties and brain function. Brain dysfunction and the cognitive functions produced emerged as one of the key factors involved in learning disabilities. Many of the theories developed around the problems of children with learning disabilities have focused on specific areas of the brain that may be dysfunctional. Conclusions: The difficulty of locating obvious brain damage in individuals who have been characterized as dyslexic leads to the strengthening of the hypothesis of the existence of a slight or minimal brain damage that cannot be easily diagnosed and strengthens the hypothesis of an unexplained brain damage that could be heterogeneous groups of learning disabilities.

Skin factor and potential formation damage from chemical and mechanical processes in a naturally fractured carbonate aquifer with implications to CO2 sequestration

In this study, we investigate formation damage due to acidization and water injection tests into the naturally fractured carbonate Middle Duperow Formation at Kevin Dome, Montana, potentially diminishing the chance of a future successful Geological Carbon Sequestration (GCS) project. Multiple well-test analytical models, correlated with core description and lithology data, are used to determine flow behavior and communication between the water injection interval and surrounding formations. An improved three-dimensional (3D) geologic model with dual-continuum matrix and fracture properties is constructed based on most recent seismic, core, and water sample measurements. Brine injection is simulated to verify the interpretation from the analytical models, followed by CO2 injection simulation. Geochemical calculations are performed to understand the in-situ processes that led to formation damage. Our findings suggest: (1) there are two possible scenarios that could lead to a positive total effective skin factor and permeability decline: partial penetration and formation damage; (2) analytical models indicate a positive total skin factor, contradicting results of a previous study suggesting that the well was mildly stimulated; (3) numerical simulation supports the formation damage hypothesis by matching the pressure buildup observed during the latter two brine injection tests; (4) several mechanical and chemical processes may have occurred during injection to clog the matrix/fracture system: anhydrite fines migration and/or calcite precipitation. We then make preventative suggestions for future GCS projects into carbonate reservoirs and remediation recommendations for GCS operation at the Kevin Dome.

Method to determine the local load cycles of a\xa0blade bearing using flexible multi-body simulation

Conventional methods for designing rolling bearings against fatigue assume that a bearing ring is fully rotating and that the load is ideally distributed over the rolling elements. Blade bearings in wind turbines, are operated under oscillating motions and dynamic loads. The load distribution is strongly dependent on the stiffness of the bearing rings and the surrounding structural components. This has been shown in numerous studies using FEM simulations for static load cases. In this paper a method is presented that reduces the calculation effort of the deformation of the bearing rings, so that a flexible integration into an aeroelastic mbs model of a wind turbine is possible. Thereby an average accuracy of 6.5% between FEM and mbs could be achieved. The model allows the determination of time series of the global load distribution of each raceway. By data processing of the simulation results, the number of load cycles and the maximum contact pressure for individual segments of the raceways could be determined and their fatigue probability could be estimated using the linear damage hypothesis according to Palmgren-Miner.