Studies of antihypertensive drug persistence and adherence in the Glasgow Blood Pressure Clinic

Hypertension (HTN) is a major risk factor for cardiovascular diseases including stroke, coronary heart disease (CHD), chronic renal failure, peripheral vascular disease, myocardial infarction, congestive heart failure and premature death. The prevalence of HTN in Scotland is very high and although a high proportion of the patients receive antihypertensive medications, blood pressure (BP) control is very low. Recommendations for starting a specific antihypertensive class have been debated between various guidelines over the years. Some guidelines and HTN studies have preferred to start with a combination of an antihypertensive class instead of using a single therapy, and they have found greater BP reductions with combination therapies than with monotherapy. However, it has been shown in several clinical trials that 20% to 35% of hypertensive patients could not achieve the target BP, even though they received more than three antihypertensive medications. Several factors were found to affect BP control. Adherence and persistence were considered as the factors contributing the most to uncontrolled hypertension. Other factors such as age, sex, body mass index (BMI), alcohol intake, baseline systolic BP (SBP), and the communication between physicians and patients have been shown to be associated with uncontrolled BP and resistant hypertension. Persistence, adherence and compliance are interchangeable terms and have been used in the literature to describe a patient’s behaviour with their antihypertensive drugs and prescriptions. The methods used to determine persistence and adherence, as well as the inclusion and exclusion criteria, vary between persistence and adherence studies. The prevalence of persistence and adherence have varied between these studies, and were determined to be high in some studies and low in others. The initiation of a specific antihypertensive class has frequently been associated with an increase or decrease in adherence and persistence. The tolerability and efficacy of the initial antihypertensive class have been the most common methods of explaining this association. There are also many factors that suggest a relationship with adherence and persistence. Some factors in previous studies, such as age, were frequently associated with adherence and persistence. On the other hand, relationships with certain factors have varied between the studies. The associations of age, sex, alcohol use, smoking, baseline systolic blood pressure (SBP) and diastolic BP (DBP), the presence of comorbidities, an increase in the number of pills and the relationship between patients and physicians with adherence and persistence have been the most commonly investigated factors. Most studies have defined persistence in terms of a patient still taking medication after a period of time. A medication possession ratio (MPR) ≥ 80 has been used to define compliance. Either of these terminologies, or both, have been used to estimate adherence. In this study, I used the same definition for persistence to identify patients who have continued with their initial treatment, and used persistence and MPR to define patients who adhered to their initial treatment. The aim of this study was to estimate the prevalence of persistence and adherence in Scotland. Also, factors that could have had an effect on persistence and adherence were studied. The number of antihypertensive drugs taken by patients during the study and factors that led to an increase in patients being on a combination therapy were also evaluated. The prevalence of resistance and BP control were determined by taking the BP after the last drug had been taken by persistent patients during five follow-up studies. The relationship of factors such as age, sex, BMI, alcohol use, smoking, estimated glomerular filtration rate (eGFR), and albumin levels with BP reductions for each antihypertensive class were determined. Information Services Division (ISD) data, which includes all antihypertensive drugs, were collected from pharmacies in Scotland and linked to the Glasgow Blood Pressure Clinic (GBPC) database. This database also includes demographic characteristics, BP readings and clinical results for all patients attending the GBPC. The case notes for patients who attended the GBPC were reviewed and all new antihypertensive drugs that were prescribed between visits, BP before and after taking drugs, and any changes in the hypertensive drugs were recorded. A total of 4,232 hypertensive patients were included in the first study. The first study showed that angiotensin converting enzyme inhibitor (ACEI) and beta-blockers (BB) were the most prescribed antihypertensive classes between 2004 and 2013. Calcium channel blockers (CCB), thiazide diuretics and angiotensin receptor blockers (ARB) followed ACEI and BB as the most prescribed drugs during the same period. The prescription trend of the antihypertensive class has changed over the years with an increase in prescriptions for ACEI and ARB and a decrease in prescriptions for BB and diuretics. I observed a difference in antihypertensive class prescriptions by age, sex, SBP and BMI. For example, CCB, thiazide diuretics and alpha-blockers were more likely to be prescribed to older patients, while ACEI, ARB or BB were more commonly prescribed for younger patients. In a second study, 4,232 and 3,149 hypertensive patients were included to investigate the prevalence of persistence in the Scottish population in 1- and 5-year studies, respectively. The prevalence of persistence in the 1-year study was 72.9%, while it was only 62.8% in the 5-year study. Those patients taking ARB and ACEI showed high rates of persistence and those taking diuretics and alpha blockers had low rates of persistence. The association of persistence with clinical characteristics was also investigated. Younger patients were more likely to totally stop their treatment before restarting their treatment with other antihypertensive drugs. Furthermore, patients who had high SBP tended to be non-persistent. In a third study, 3,085 and 1,979 patients who persisted with their treatment were included. In the first part of the study, MPR was calculated, and patients with an MPR ≥ 80 were considered as adherent. Adherence rates were 29.9% and 23.4% in the 1- and 5-year studies, respectively. Patients who initiated the study with ACEI were more likely to adhere to their treatments. However, patients who initiated the study with thiazide diuretics were less likely to adhere to their treatments. Sex, age and BMI were different between the adherence and non-adherence groups. Age was an independent factor affecting adherence rates during both the 1- and 5-year studies with older patients being more likely to be adherent. In the second part of the study, pharmacy databases were checked with patients' case notes to compare antihypertensive drugs that were collected from the pharmacy with the antihypertensive prescription given during the patient’s clinical visit. While 78.6% of the antihypertensive drugs were collected between clinical visits, 21.4% were not collected. Patients who had more days to see the doctor in the subsequent visit were more likely to not collect their prescriptions. In a fourth study, 3,085 and 1,979 persistent patients were included to calculate the number of antihypertensive classes that were added to the initial drug during the 1-year and 5-year studies, respectively. Patients who continued with treatment as a monotherapy and who needed a combination therapy were investigated during the 1- and 5-year studies. In all, 55.8% used antihypertensive drugs as a monotherapy and 44.2% used them as a combination therapy during the 1-year study. While 28.2% of patients continued with treatment without the required additional therapy, 71.8% of the patients needed additional therapy. In all, 20.8% and 46.5% of patients required three different antihypertensive classes or more during the 1-year and 5-year studies, respectively. Patients who started with ACEI, ARB and BB were more likely to continue as monotherapy and less likely to need two more antihypertensive drugs compared with those who started with alpha-blockers, non-thiazide diuretics and CCB. Older ages, high BMI levels, high SBP and high alcohol intake were independent factors that led to an increase in the probability of patients taking combination therapies. In the first part of the final study, BPs were recorded after the last drug had been taken during the 5 year study. There were 815 persistent patients who were assigned for this purpose. Of these, 39% had taken one, two or three antihypertensive classes and had controlled BP (controlled hypertension [HTN]), 29% of them took one or two antihypertensive classes and had uncontrolled BP (uncontrolled HTN), and 32% of the patients took three antihypertensive classes or more and had uncontrolled BP (resistant HTN). The initiation of an antihypertensive drug and the factors affecting BP pressure were compared between the resistant and controlled HTN groups. Patients who initiated the study with ACEI were less likely to be resistant compared with those who started with alpha blockers and non-thiazide diuretics. Older patients, and high BMI tended to result in resistant HTN. In the second part of study, BP responses for patients who initiated the study with ACEI, ARB, BB, CCB and thiazide diuretics were compared. After adjusting for risk factors, patients who initiated the study with ACEI and ARB were more respondent than those who took CCB and thiazide diuretics. In the last part of this study, the association between BP reductions and factors affecting BP were tested for each antihypertensive drug. Older patients responded better to alpha blockers. Younger patients responded better to ACEI and ARB. An increase in BMI led to a decreased reduction in patients on ACEI and diuretics (thiazide and non-thiazide). An increase in albumin levels and a decrease in eGFR led to decreases in BP reductions in patients on thiazide diuretics. An increase in eGFR decreased the BP response with ACEI. In conclusion, although a high percentage of hypertensive patients in Scotland persisted with their initial drug prescription, low adherence rates were found with these patients. Approximately half of these patients required three different antihypertensive classes during the 5 years, and 32% of them had resistant HTN. Although this study was observational in nature, the large sample size in this study represented a real HTN population, and the large pharmacy data represented a real antihypertensive population, which were collected through the support of prescription data from the GBPC database. My findings suggest that ACEI, ARB and BB are less likely to require additional therapy. However, ACEI and ARB were better tolerated than BB in that they were more likely to be persistent than BB. In addition, users of ACEI, and ARB have good BP response and low resistant HTN. Linkage patients who participated in these studies with their morbidity and mortality will provide valuable information concerning the effect of adherence on morbidity and mortality and the potential benefits of using ACEI or ARB over other drugs.

Relationship between internal derangement of temporomandibular joint and changes in body posture

Background: The presence of body posture changes among patients with temporomandibular disorders (TMD) has been a controversial issue in the literature, in which it supporters point out the muscular origin as the main etiological factors, mainly associated with postural changes in head. Due to this controversy, it is pertinent to check whether this relationship exists on the most common etiology of TMD, the disk displacement, which translates a biomechanical internal disorder of the temporomandibular joint (TMJ). Objectives: Assess body posture changes in subjects with internal derangement of the TMJ when compared to subjects without this biomechanical dysfunction, characterize the patterns of the jaw movements and assess to the muscle activation during jaw movements. Methods: 21 subjects with TMJ disc displacement (DD) (test group) and 21 subjects without any TMD (control group) was assessed for body posture changes through evaluation of several body segments by posturography and also was evaluated the postural balance reactions through the center of mass during jaw movements using a balance platform. For the characterization of the jaw movement patterns it was done a kinematic analysis during jaw movements (active ROM and path of the jaw). For the muscle activation during jaw movements it was evaluated the masseter, sternocleidomastoid and spinae erector muscles by surface electromyography (EMG). Results Discussion: Both groups show forward head posture and extension of the cervical spine, not noticing any other significant body posture changes in subjects with DD, and if we had to see in detail, in general, subjects without TMD shows more body posture changes than subjects with DD. The pattern of jaw movements is similar in both groups, but in subjects with DD the closing movements are more instable than the opening movements, related to a less effective movement control to counteract the force of gravity and the disk displacement. The bilateral muscle activation during jaw movements is higher in subjects with DD, likely related to a less stable pattern of movement which leads in a higher muscle activation to guide the movement and ensure the best as possible articular stability. Conclusion: The disk displacement with reduction should be viewed as part of a set of signs and symptoms that require an accurate musculoskeletal and psychosocial assessment towards an earlier diagnosis for reduction and control of the functional limiting factors. In this direction, it seems that the relevant set of limiting signs and symptoms deserve a particular attention by health care practitioners involved in the assessment and treatment of TMD, in order to define effective therapeutic options.

Rail passenger crowding, stress, health and safety in Britain

There has long been a question as to whether crowding in rail passenger transport poses a threat to passenger health related to the experience of stress. A review of the scientific literature was conducted. Little rail-specific empirical research was identified. The more general research that does exist suggests that high-density environments are not necessarily perceived as crowded and that stress-related physiological, psychological and behavioural reactions do not necessarily follow from exposure to such environments. Several factors are identified that may moderate the impact of a high-density environment on perceptions of crowding and the subsequent experience and effects of stress. These include, inter alia, perceptions of control and predictability of events. However, if caused, the experience and effects of stress may be made worse by inadequate coach design that gives rise to discomfort. The model that emerges from these findings offers a suitable framework for the development of research questions that should help translate emerging knowledge into practical interventions, for the reduction of any adverse health outcomes associated with crowding.

A Learning Function for Parameter Reduction in Spiking Neural Networks with Radial Basis Function

Spiking neural networks - networks that encode information in the timing of spikes - are arising as a new approach in the artificial neural networks paradigm, emergent from cognitive science. One of these new models is the pulsed neural network with radial basis function, a network able to store information in the axonal propagation delay of neurons. Learning algorithms have been proposed to this model looking for mapping input pulses into output pulses. Recently, a new method was proposed to encode constant data into a temporal sequence of spikes, stimulating deeper studies in order to establish abilities and frontiers of this new approach. However, a well known problem of this kind of network is the high number of free parameters - more that 15 - to be properly configured or tuned in order to allow network convergence. This work presents for the first time a new learning function for this network training that allow the automatic configuration of one of the key network parameters: the synaptic weight decreasing factor.

The effect of chaperone compounds on glucocerebrosidase stability and activity in fibroblasts from Gaucher Disease patients with different genotypes

Dissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2014

Beech bark disease distribution and resistance in Michigan and fungal endophyte ecology of resistant and susceptible beech (Fagus grandifolia Ehrh.)

Beech bark disease (BBD), a non-native association of the fungal pathogen Neonectria faginata and the beech scale insect Cryptococcus fagisuga, has dramatically affected American beech within North American forests. To monitor the spread and effects of BBD in Michigan, a network of forest health monitoring plots was established in 2001 following the disease discovery in Ludington State Park (Mason County). Forest health canopy condition and basic forestry measurements including basal area were reassessed on beech trees in these plots in 2011 and 2012. The influence of bark-inhabiting fungal endophytes on BBD resistance was investigated by collecting cambium tissue from apparently resistant and susceptible beech. Vigor rating showed significant influences of BBD in sample beech resulting in reduced health and substantiated by significant increases of dead beech basal area over time. C. fagisuga distribution was found to be spatially clustered and widespread in the 22 counties in Michigan's Lower Peninsula which contained monitoring plots. Neonectria has been found in Emmet, Cheboygan and Wexford in the Lower Peninsula which may coincide with additional BBD introduction locations. Surveys for BBD resistance resulted in five apparently resistant beech which were added to a BBD resistance database. The most frequently isolated endophytes from cambium tissue were identified by DNA sequencing primarily as Deuteromycetes and Ascomycetes including Chaetomium globosum, Neohendersonia kickxii and Fusarium flocciferum. N. faginata in antagonism trials showed significant growth reduction when paired with three beech fungal endophytes. The results of the antagonism trial and decay tests indicate that N. faginata may be a relatively poor competitor in vivo with limited ability to degrade cellulose.

Using a modified Nordmore grid for by-catch reduction in the Portuguese crustacean-trawl fishery

By-catch and discards are a common problem to all fisheries. Recent studies of the Portuguese crustacean-trawl fishery show that discards average 70% of the total catch. This situation poses a threat not only to the management of target and commercial fish by-catch species stocks, but also in terms of the ecosystem impact of the discarded species whose survival is generally low. Previous attempts to address this problem by using oblique separator mesh panels associated with square-mesh windows, or square-mesh windows alone, provided encouraging results, but these are unlikely to have commercial applicability at present. Therefore, we tested the efficiency of a modified Nordmore grid in excluding some of the most captured non-commercial by-catch species, such as the blue whiting, Micromesistius poutassou, and the boarfish, Capros aper, evaluating simultaneously the losses of the crustacean target species (rose shrimp, Parapenaeus longirostris, Norway lobster, Nephrops norvegicus and red shrimp, Aristeus antennatus) and commercially valuable fish by-catch. A total of 41 valid hauls were carried out during 2001, and 15 in 2002 on board the R/V "Noruega". Results from both years varied considerably, with higher by-catch exclusion rates, in weight, registered in the second survey (73-74 and 48-63% for blue whiting and boarfish, respectively). The corresponding percentage reduction for target species was 8-15% for the Norway lobster, 4-9% for rose shrimp and 7-10% for red shrimp. The level of exclusion of the non-commercial by-catch is encouraging, although short-term loss of Norway lobster, where the escapees comprised larger individuals, raises some concern with regards to fishers' acceptance of mandatory use of grids. (C) 2004 Elsevier B.V. All rights reserved.

Starch, growth, and development in cuttings of rootstock "Paulsen 1103" from plants infested with ground pearl.

ABSTRACT The ground pearl, Eurhizococcus brasiliensis, is considered an important pest of vineyards in southern Brazil, with affected plants exhibiting leaf chlorosis, reduction in vigor, fading, and death. This study evaluated the quality of hardwood cuttings produced from plants infected (I) and not infected (NI) by ground pearl. ?Paulsen 1103? (Vitis berlandieri × Vitis rupestris) plants were grown for 29 months in brick-built raised beds either infested or not infested by ground pearl; then, 12 one-year-old branches with a maximum of 12 buds each were cut from each plant, subdivided into three portions (4 buds cutting-1), and subjected to destructive and nondestructive testing. Destructive testing comprised determining fresh and dry weight, length, internode diameters, and percentage of starch. Nondestructive testing comprised assessing the potential for bud sprouting and shoot development. Each mother plant in the I and NI beds was considered a replicate, with a total of 360 cuttings per treatment. It was observed that cuttings from infected plants had significantly lower (P<0.05) internode diameter, length, and fresh and dry weight than those of the uninfected plants. The percentage of starch content of the cuttings did not differ significantly. All cuttings showed the same percentage (100%) of bud breaking and no changes in growth and development of seedlings regardless of source. Given these results, it was concluded that vines of ?Paulsen 1103? infested with ground pearl produce smaller cuttings than those of uninfected plants but with no reduction in bud break percentage or seedling development. Key words: Margarodidae, Vitaceae, insect?plant interaction, carbohydrates. RESUMO A pérola-da-terra, Eurhizococcus brasiliensis, tem sido considerada uma importante praga dos vinhedos no sul do Brasil, sendo que as plantas atacadas manifestam clorose foliar, redução no vigor, definhamento e morte. Este trabalho teve por objetivo avaliar a qualidade de estacas lenhosas produzidas a partir do contraste de videiras infestadas (I) e não infestadas (NI) por pérola-da-terra. Após 29 meses de cultivo em canteiros de alvenaria, em presença ou ausência de pérola-da-terra, cada planta da variedade ?Paulsen 1103? (Vitis berlandieri × Vitis rupestris) foi submetida à retirada de 12 ramos de ano, com no máximo 12 gemas cada, sendo subdivididos em três porções 4 gemas estaca-1) e submetidos a avaliações destrutivas e não destrutivas. As destrutivas consistiram em determinar massas fresca e seca, comprimento, diâmetro de entrenós e percentual de amido. As avaliações não estrutivas consistiram em testar o potencial de brotação e desenvolvimento das estacas. Cada planta matriz dos canteiros I e NI foi considerada uma repetição, totalizando 360 estacas por tratamento. As estacas das plantas infestadas tiveram uma redução (P<0,05), em relação às não infestadas, em diâmetro, comprimento e massas fresca e seca. Não houve contraste significativo do percentual de amido avaliado das estacas. Quanto à brotação, destaca-se que todas as estacas apresentaram o mesmo percentual (100%), independente da origem, sem alterações no desenvolvimento e crescimento das mudas. Diante desses resultados, salienta-se que videiras ?Paulsen 1103? infestadas por pérola-da-terra produzem estacas menores, porém não há comprometimento no percentual de brotação e desenvolvimento das mudas, quando comparadas com plantas não infestadas. Palavras-chave: Margarodidae, Vitaceae, interação inseto-planta, carboidrato

Prediction of a low-risk concentration of diflubenzuron to aquatic organisms and evaluation of clay and gravel in reducing the toxicity.

Resumo: Predição da concentração de baixo risco de diflubenzuron para organismos aquáticos e avaliação da argila e brita na redução da toxicidade. O diflubenzuron é um inseticida que além de ser usado agricultura, tem sido amplamente empregado na piscicultura, apesar do seu uso ser proibido nesta atividade. Este composto não consta na lista da legislação brasileira que estabelece limites máximos permissíveis em corpos de água para a proteção das comunidades aquáticas. No presente trabalho, a partir da toxicidade do diflubenzuron em organismos não-alvo, foi calculada a concentração de risco para somente 5% das espécies (HC5). O valor deste parâmetro foi estimado em aproximadamente 7 x 10-6 mg L-1 . Este baixo valor é devido à extremamente alta toxicidade do diflubenzuron para dafnídeos e à grande variação de sensibilidade entre as espécies testadas. Dois matérias de relativamente baixo custo se mostraram eficientes na remoção da toxicidade do diflubenzuron de soluções contendo este composto. Dentre esses materiais, a argila expandida promoveu a redução em aproximadamente 50% da toxicidade de uma solução contendo diflubenzuron. Os resultados podem contribuir para políticas públicas no Brasil relacionadas ao estabelecimento de limites máximos permissíveis de xenobióticos no compartimento aquático. Também, para a pesquisa de matérias inertes e de baixo custo com potencial de remoção de xenobióticos presentes em efluentes da aquicultura ou da agricultura. Abstract: Diflubenzuron is an insecticide that, besides being used in the agriculture, has been widely used in fish farming. However, its use is prohibited in this activity. Diflubenzuron is not in the list of Brazilian legislation establishing maximum permissible limits in water bodies for the protection of aquatic communities. In this paper, according toxicity data of diflubenzuron in non-target organisms, it was calculated an hazardous concentration for only 5% of the species (HC5) of the aquatic community. This parameter value was estimated to be about 7 x 10 -6 mg L -1 . The low value is due to the extreme high toxicity of diflubenzuron to daphnids and to the large variation in sensitivity among the species tested. Two relatively low cost and inert materials were efficient in removing the diflubenzuron from solutions containing this compound. Among these materials, expanded clay shown to promote reduction of approximately 50% of the toxicity of a solution containing diflubenzuron. The results may contribute to the establishment of public policies in Brazil associated to the definition of maximum permissible limits of xenobiotics in the aquatic compartment. This study is also relevant to the search of low cost and inert materials for xenobiotics removal from aquaculture or agricultural effluents.

Altered transcriptional and epigenetic regulation affects brain cells proliferation and differentiation in the ultra-rare genetic demyelinating disease AGC1 deficiency: a study on in vitro models

AGC1 deficiency is a rare demyelinating disease caused by mutations in the SLC25A12 gene, which encodes for the mitochondrial glutamate-aspartate carrier 1 (AGC1/Alarar), highly expressed in the central nervous system. In neurons, impairment in AGC1 activity leads to reduction in N-acetyl-aspartate, the main lipid precursor for myelin synthesis (Profilo et al., 2017); in oligodendrocytes progenitors cells, AGC1 down regulation has been related to early arrest proliferation and premature differentiation (Petralla et al., 2019). Additionally, in vivo AGC1 deficiency models i.e., heterozygous mice for AGC1 knock-out and neurospheres from their subventricular zone, respectively, showed a global decrease in cells proliferation and a switch in neural stem cells (NSCs) commitment, with specific reduction in OPCs number and increase in neural and astrocytic pools (Petralla et al., 2019). Therefore, the present study aims to investigate the transcriptional and epigenetic regulation underlying the alterations observed in OPCs and NSCs biological mechanisms, in either AGC1 deficiency models of Oli-neu cells (murine immortalized oligodendrocytes precursors cells), partially silenced by a shRNA for SLC25A12 gene, and SVZ-derived neurospheres from AGC1+/- mice. Western blot and immunofluorescence analysis revealed significant variations in the expression of transcription factors involved in brain cells’ proliferation and differentiation, in association with altered histone post-translational modifications, as well as histone acetylases (HATs) and deacetylases (HDACs) activity/expression, suggesting an improper transcriptional and epigenetic regulation affecting both AGC1 deficiency in vitro models. Furthermore, given the large role of acetylation in controlling in specific time-windows OPC maturation (Hernandez and Casaccia; 2015), pharmacological HATs/HDACs inhibitions were performed, confirming the involvement of chromatin remodelling enzymes in the altered proliferation and early differentiation observed in the AGC1 deficiency models of siAGC1 Oli-neu cells and AGC1+/- mice-derived neurospheres.

An Asp49 Phospholipase A2 From Snake Venom Induces Cyclooxygenase-2 Expression And Prostaglandin E2 Production Via Activation Of Nf-κb, P38mapk, And Pkc In Macrophages.

Phospholipases A2 (PLA2) are key enzymes for production of lipid mediators. We previously demonstrated that a snake venom sPLA2 named MT-III leads to prostaglandin (PG)E2 biosynthesis in macrophages by inducing the expression of cyclooxygenase-2 (COX-2). Herein, we explored the molecular mechanisms and signaling pathways leading to these MT-III-induced effects. Results demonstrated that MT-III induced activation of the transcription factor NF-κB in isolated macrophages. By using NF-κB selective inhibitors, the involvement of this factor in MT-III-induced COX-2 expression and PGE2 production was demonstrated. Moreover, MT-III-induced COX-2 protein expression and PGE2 release were attenuated by pretreatment of macrophages with SB202190, and Ly294002, and H-7-dihydro compounds, indicating the involvement of p38MAPK, PI3K, and PKC pathways, respectively. Consistent with this, MT-III triggered early phosphorylation of p38MAPK, PI3K, and PKC. Furthermore, SB202190, H-7-dihydro, but not Ly294002 treatment, abrogated activation of NF-κB induced by MT-III. Altogether, these results show for the first time that the induction of COX-2 protein expression and PGE2 release, which occur via NF-κB activation induced by the sPLA2-MT-III in macrophages, are modulated by p38MAPK and PKC, but not by PI3K signaling proteins.

Beam-energy Dependence Of The Directed Flow Of Protons, Antiprotons, And Pions In Au+au Collisions.

Rapidity-odd directed flow (v1) measurements for charged pions, protons, and antiprotons near midrapidity (y=0) are reported in sNN=7.7, 11.5, 19.6, 27, 39, 62.4, and 200 GeV Au+Au collisions as recorded by the STAR detector at the Relativistic Heavy Ion Collider. At intermediate impact parameters, the proton and net-proton slope parameter dv1/dy|y=0 shows a minimum between 11.5 and 19.6 GeV. In addition, the net-proton dv1/dy|y=0 changes sign twice between 7.7 and 39 GeV. The proton and net-proton results qualitatively resemble predictions of a hydrodynamic model with a first-order phase transition from hadronic matter to deconfined matter, and differ from hadronic transport calculations.

Structural Connectivity Of The Default Mode Network And Cognition In Alzheimer׳s Disease.

Disconnectivity between the Default Mode Network (DMN) nodes can cause clinical symptoms and cognitive deficits in Alzheimer׳s disease (AD). We aimed to examine the structural connectivity between DMN nodes, to verify the extent in which white matter disconnection affects cognitive performance. MRI data of 76 subjects (25 mild AD, 21 amnestic Mild Cognitive Impairment subjects and 30 controls) were acquired on a 3.0T scanner. ExploreDTI software (fractional Anisotropy threshold=0.25 and the angular threshold=60°) calculated axial, radial, and mean diffusivities, fractional anisotropy and streamline count. AD patients showed lower fractional anisotropy (P=0.01) and streamline count (P=0.029), and higher radial diffusivity (P=0.014) than controls in the cingulum. After correction for white matter atrophy, only fractional anisotropy and radial diffusivity remained significantly lower in AD compared to controls (P=0.003 and P=0.05). In the parahippocampal bundle, AD patients had lower mean and radial diffusivities (P=0.048 and P=0.013) compared to controls, from which only radial diffusivity survived for white matter adjustment (P=0.05). Regression models revealed that cognitive performance is also accounted for by white matter microstructural values. Structural connectivity within the DMN is important to the execution of high-complexity tasks, probably due to its relevant role in the integration of the network.

Impaired Compensatory Beta-cell Function And Growth In Response To High-fat Diet In Ldl Receptor Knockout Mice.

In this study, we investigated the effect of low density lipoprotein receptor (LDLr) deficiency on gap junctional connexin 36 (Cx36) islet content and on the functional and growth response of pancreatic beta-cells in C57BL/6 mice fed a high-fat (HF) diet. After 60 days on regular or HF diet, the metabolic state and morphometric islet parameters of wild-type (WT) and LDLr-/- mice were assessed. HF diet-fed WT animals became obese and hypercholesterolaemic as well as hyperglycaemic, hyperinsulinaemic, glucose intolerant and insulin resistant, characterizing them as prediabetic. Also they showed a significant decrease in beta-cell secretory response to glucose. Overall, LDLr-/- mice displayed greater susceptibility to HF diet as judged by their marked cholesterolaemia, intolerance to glucose and pronounced decrease in glucose-stimulated insulin secretion. HF diet induced similarly in WT and LDLr-/- mice, a significant decrease in Cx36 beta-cell content as revealed by immunoblotting. Prediabetic WT mice displayed marked increase in beta-cell mass mainly due to beta-cell hypertrophy/replication. Nevertheless, HF diet-fed LDLr-/- mice showed no significant changes in beta-cell mass, but lower islet-duct association (neogenesis) and higher beta-cell apoptosis index were seen as compared to controls. The higher metabolic susceptibility to HF diet of LDLr-/- mice may be explained by a deficiency in insulin secretory response to glucose associated with lack of compensatory beta-cell expansion.

Perception Of Oral And Maxillofacial Surgeons, Orthodontists And Laypersons In Relation To The Harmony Of The Smile.

Harmony is one of the main objectives in surgical and orthodontic treatment and this harmony must be present in the smile, as well as in the face. The aim of the present study was to assess the perceptions of professionals and laypersons in relation to the harmony of the smile of patients with or without vertical maxillary alterations. Sixty observers (oral and maxillofacial surgeons, orthodontists and laypersons) reported the degree of harmony of six smiles using an objective questionnaire and the participants indicated if there was a need for corrective surgery or not. The classification of observers was recorded on a Likert scale from 1 to 5. Mixed regression was used to determine differences between the three groups. Statistically significant differences were found only for the harmony of the smile between the oral and maxillofacial surgeons and laypersons, with laypersons being more critical when assessing the smile. There was no statistical difference between the other groups for the harmony of the smile or the indication of corrective surgery. The patterns of greater or lesser harmony determined by observers during the smile were similar to those found in the literature as the ideal standard in relation to vertical maxillary positioning. Laypersons had a tendency to be more critical in relation to facial harmony than surgeons, although no statistical differences were found in the other groups in relation to the harmony of the smile or indication for the corrective surgery. In addition, the patterns of greater or lesser harmony of the smile determined by the participants were similar to those found in the literature as the ideal standard in relation to vertical maxillary positioning. Overall, the present study demonstrates that adequate interaction between surgeons, orthodontists and laypersons is essential in order to achieve facial harmony with orthodontic and/or surgical treatment. Opinion of specialists and laypersons about the smile in relation to the vertical positioning of the maxilla.