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Abstract: In this work we propose a new biophysical computational model of brain regions relevant to Parkinson's Disease (PD) based on local field potential data collected from the brain of marmoset monkeys. PD is a neurodegenerative disorder, linked to the death of dopaminergic neurons at the substantia nigra pars compacta, which affects the normal dynamics of the basal ganglia-thalamus-cortex (BG-T-C) neuronal circuit of the brain. Although there are multiple mechanisms underlying the disease, a complete description of those mechanisms and molecular pathogenesis are still missing, and there is still no cure. To address this gap, computational models that resemble neurobiological aspects found in animal models have been proposed. In our model, we performed a data-driven approach in which a set of biologically constrained parameters is optimised using differential evolution. Evolved models successfully resembled spectral signatures of local field potentials and single-neuron mean firing rates from healthy and parkinsonian marmoset brain data. This is the first computational model of PD based on simultaneous electrophysiological recordings from seven brain regions of Marmoset monkeys. Results indicate that the proposed model may facilitate the investigation of the mechanisms of PD and eventually support the development of new therapies. The DE method could also be applied to other computational neuroscience problems in which biological data is used to fit multi-scale models of brain circuits

Abstract: Using a urethral device at the fossa navicularis, bladder pressure during voiding can be estimated by a minimal invasive technique. This study purposes a new diagnostic index for patients with lower urinary tract symptoms (LUTSs). Fifty one patients presenting with LUTSs were submitted to a conventional urodynamic and a minimal invasive study. The results obtained through the urethral device and invasive classic urodynamics were compared. The existing bladder outlet obstruction index (BOOI) equation that classifies men with LUTSs was modified to allow minimal invasive measurement of isovolumetric bladder pressure in place of detrusor pressure at maximum urine flow. Accuracy of the new equation for classifying obstruction was then tested in this group of men. The modified equation identified men with obstruction with a positive predictive value of 68% and a negative predictive value of 70%, with an overall accuracy of 70%. The proposed equation can accurately classify over 70% of men without resorting to invasive pressure flow studies. We must now evaluate the usefulness of this classification for the surgical treatment of men with LUTSs

Abstract: Inflammation is the most relevant mechanism linking obesity with insulin-resistance and metabolic disease. It impacts the structure and function of tissues and organs involved in metabolism, such as the liver, pancreatic islets and the hypothalamus. Brown adipose tissue has emerged as an important component of whole body energy homeostasis, controlling caloric expenditure through the regulation of non-shivering thermogenesis. However, little is known about the impact of systemic inflammation on the structure and function of brown adipose tissue. The relations between IL10 and mitochondria structure/function and also with thermogenesis were evaluated by bioinformatics using human and rodent data. Real-time PCR, immunoblot, fluorescence and transmission electron microscopy were employed to determine the effect of IL10 in the brown adipose tissue of wild type and IL10 knockout mice. IL10 knockout mice, a model of systemic inflammation, present severe structural abnormalities of brown adipose tissue mitochondria, which are round-shaped with loss of cristae structure and increased fragmentation. IL10 deficiency leads to newborn cold intolerance and impaired UCP1-dependent brown adipose tissue mitochondrial respiration. The reduction of systemic inflammation with an anti-TNFa monoclonal antibody partially rescued the structural but not the functional abnormalities of brown adipose tissue mitochondria. Using bioinformatics analyses we show that in both humans and mice, IL10 transcripts correlate with mitochondrial lipid metabolism and caspase gene expression. IL10 and systemic inflammation play a central role in the regulation of brown adipose tissue by controlling mitochondrial structure and function

External electric fields (E) induce a spatially heterogeneous variation in the membrane potential (Delta V-m) of cardiomyocytes that, if sufficiently large, results in an action potential and contraction. Insights into the phenomenon of Delta V-m induction by E have been classically gained with electromagnetic models due to the lack of adequate experimental approaches. However, it is not clear yet how reliable these models are. To assess the accuracy of commonly used models, a reference 3D numerical model for cardiomyocytes (NMReal) was developed, consisting of the cell membrane shell reconstructed from rendered confocal microscopy images of freshly isolated ventricular myocytes. NMReal was used to estimate the E-induced maximum Delta V-m values (Delta V-max), which were compared with estimates from seven other electromagnetic models. Accurate Delta V-max estimates (average error < 2%) were obtained with a less complex 3D model (NM3D) based on the extruded 2D image of the cell longitudinal section. Acceptable Delta V-max estimates (average error < 5%) were obtained with the prolate spheroid analytical model (PSAM) when the angle of E incidence and the cell major axis was < 30 degrees. In this case, PSAM, a much simpler model requiring only the measurement of the longitudinal and transversal cell dimensions, can be a suitable alternative for Delta V-max calculation

Abstract: Objectives: Standard prognostic markers based on individual characteristics of individuals with multiple myeloma (MM) remain scarce. Body-composition features have often been associated with survival outcomes in different cancers. However, the association of adipose tissue radiodensity with MM prognosis has not yet, to our knowledge, been explored. Methods: Computed tomography at the third lumbar vertebra was used for body-composition analysis, including adipose tissue radiodensity, in 91 people with MM. Additionally, fludeoxyglucose F 18 (F-18-FDG) positron emission tomography was used to assess adipose tissue F-18-FDG uptake. Proinflammatory cytokine and adipokine levels were measured. Results: Event-free survival and overall survival were both shorter in participants with high subcutaneous adipose tissue (SAT) radiodensity. Those in the highest SAT radiodensity tertile had an independently higher risk for both overall survival (hazard ratio, 4.55; 95% confidence interval, 1.26-16.44; P-trend = 0.036) and event-free survival (hazard ratio, 3.08; 95% confidence interval, 1.02-9.27; P-trend = 0.035). Importantly, higher SAT radiodensity was significantly correlated with increased F-18-FDG adipose tissue uptake and proinflammatory cytokine (tumor necrosis factor and interleukin-6) levels, and with decreased leptin levels. Conclusions: SAT radiodensity may serve as a biomarker to predict host-related metabolic and proinflammatory milieu, which ultimately correlates with MM prognosis

Resumo: Dentre os equipamentos utilizados em circulação extracorpórea, as bombas de rolete têm grande importância, com diversos modelos disponíveis de vários fabricantes. A calibração é um fator importante nas taxas de hemólise e o seu potencial difere em cada uma delas. Pesquisadores nem sempre abordam detalhes sobre os perfis do leito rígido, supondo que as formas padronizadas de calibração garantem valores iguais e comparáveis para todos os modelos de bombas de rolete. Dispomos principalmente de dois métodos para a calibração das bombas, o que também interfere com o potencial hemolítico. Nenhum dos métodos considera as características de impulsão do fluído, definido pela forma construtiva do leito rígido. O objetivo é avaliar o perfil hidrodinâmico de três modelos de bombas de roletes disponíveis no mercado brasileiro. A oclusão dos roletes foi feita por medidas de velocidade de queda e calibração dinâmica. Foram utilizados dois diferentes diâmetros de tubos de silicone (3/8 x 1/16 e 1/2 x 3/32 polegadas). Os perfis apresentaram diferenças em suas variâncias. P<0,01 para medidas de velocidade de queda e P<0,0001 para medidas de calibração dinâmica. Foram encontradas diferenças nas variações de pressão entre as bombas analisadas (P<0,002). As medidas de oclusão são dependentes da forma do leito rígido e comparações envolvendo bombas de rolete devem ser feitas com cautela. Testes com sangue deveriam ser realizados para verificar a influência das variações de pressão na hemólise

Abstract: The isolated cardiomyocyte preparation is amenable to several experimental approaches not suitable to the myocardial tissue, which has allowed the gain of important information on the pathophysiology of the cardiac muscle. Thus, the development of techniques for functional studies in this preparation is important. The goal of the present study was to develop a computer program to extract contraction traces generated by cyclic cell shortening from cardiomyocyte video image files. The Canny algorithm, widely used for computer vision, was implemented for cell edge recognition and continuous tracking, so that changes in cardiomyocyte length could be monitored. The program was applied to demonstrate the effect of classical inotropic maneuvers on contraction parameters, as well as to assess the development of spontaneous activity in response to defibrillator-like electrical shocks in rat isolated cardiomyocytes. The method resulted in successful monitoring of variations in cell length during both electrically-triggered and post-shock spontaneous contractions, of which the rate was significantly related to shock strength. The proposed approach might be useful for analysis of contractile activity of isolated muscle cells, and allows detection of even the typically low-amplitude noisy spontaneous contractile events. Additionally, the experimental data suggest that the rate of spontaneous contraction could be used as an index of shock-induced electrical membrane damage

Although increase in heart rate is a crucial determinant for enhancement of cardiac output in the neonate, information on the chronotropic reactivity to catecholamines during postnatal development is scarce. The present study was aimed at investigating the role of P-adrenoceptor subtypes and catecholamine removal mechanisms in the adrenergic chronotropic response during the early post natal period. Right atria isolated from immature (0-21 day old) and adult (4-6 month old) rats were used for determination of the responsiveness to agonists and quaraitation of the transcripts of proteins involved in beta-adrenergic signaling. The main results were: (a) the maximum response (R-max) to norepinephrine increased with age, whereas sensitivity decreased; (b) age dependent differences in sensitivity to nor epinephrine were abolished by inhibition of the neuronal norepinephrine transporter; (c) R-max to isoproterenol was similar in immature and adult atria, and depressed only in the former by beta(2)-adrenoceptor blockade with ICI118,551; (d) neonatal atria showed greater beta(2)-adrenoceptor mRNA levels, and more prominent positive chronotropic response to the beta(2)- and beta(3)-adrenoceptor agonists zinterol and YM178, respectively (nanomolar range); (e) in atria of immature rats, transcript levels of the extraneuronal monoamine transporter were lower, and its inhibition did not affect sensitivity to isoproterenol; and (f) reactivity to forskolin and 3-isobutyl-1-methylxanthine was not affected by age. The increased beta(2)- and beta(3)-adrenoceptor participation in the adrenergic chronotropic response, in addition to weaker catecholamine removal, may compensate for the immature cardiac innervation and the apparently reduced efficiency of beta(1)-adrenoceptor signaling in the neonate, increasing the responsiveness to endogenous and exogenous beta(2)-adrenoceptor agonists

Roller pumps are commonly used in surgeries involving extracorporeal circulation and its regulation may influence the hemolysis rate. To describe an auxiliary device for adjusting roller pumps using the dynamic calibration method and show preliminary results of its application in surgical procedures. The device was tested in the laboratory environment with three disposable pressure transducers normally used in surgeries. In the operation room, tests were carried out with two groups of patients. Free hemoglobin plasma rates were measured, 5 minutes after perfusion started and immediately before the passage of the residual volume of the pump. For Group 1 (n = 22), occlusion measurements were carried out using the drop rate method and for Group 2 (n = 18), measurements were carried out using the auxiliary device and 300 mmHg calibration (mean pressure for the dynamic calibration method). The auxiliary calibration device has shown calibration results statistically equal to those obtained with a reference device in the laboratory environment. We have found less variability of hemolysis rates in the operating room, using the auxiliary device and we did not observe any influence of unbalanced rollers in the hemolysis rates.

The insect heart (dorsal vessel, DV) is considered a valuable model for studies on cardiac genetics, development, and physiology. However, as software for monitoring and quantitation of insect cardiac activity is not commercially available, most studies depend on time-consuming, post hoc analysis of video records. In this study, a computer program (BugHeart) was developed for this purpose, and applied to the determination of the octopamine effects on Tenebrio molitor DV. Methods: The software was developed in Labview 11.0 for online processing of amplified video images of the transilluminated DV, in which systolic variation of the luminal diameter can be monitored over successive contraction cycles by video-tracking the tube inner edge. The possibility of adjustment of light intensity threshold and the introduction of calibration allow online quantitation of the DV luminal diameter and its cyclic variation (contraction amplitude), as well as heart rate (HR) estimation. The program can export video and text files for documentation and further analysis. Results: BugHeart showed to be user-friendly and to allow continuous assessment of the preparation stability and response to drugs. Post hoc estimation of fractional vessel shortening (FS) and contraction temporal parameters was possible by applying simple calculations to the exported data. Octopamine produced significant cardioacceleration at 1 μM, while at 10 μM it also increased FS and abbreviated relaxation. Conclusions: By providing online monitoring of cardiac activity and facilitating parameter estimation, BugHeart proved to be a useful tool and allowed characterization of octopamine cardiostimulatory effects in T. molitor—here reported for the first time

Resumo: Categorizar a vitimização por bullying e cyberbullying em adolescentes. Trata-se de um estudo quantitativo, descritivo, exploratório, transversal, com estudantes adolescentes de duas escolas públicas e duas particulares que respondeream um questionário, em seguida, empregou-se o instrumento Multidimentional Peer Victimation Scale adaptado para a mensuração do bullying. Utilizou-se o teste Kruskal-Wallis para a comparação entre médias e a correlação de Pearson para relacionar as variáveis estudadas com as ocorrências de vitimização. Revela-se que aproximadamente 78% dos estudantes das escolas relataram, pelo menos, uma ocorrência de bullying nos últimos seis meses e 17% sofreram metade das vitimizações totais no mesmo período. Mostraram-se, pela média do bullying entre as escolas, diferenças significantes, e a comparação com dados da literatura indicou preocupação nos graus moderado e severo. Conclui-se que as classificações das vitimizações foram consistentes com a literatura. Observaram-se diferenças nas características das vítimas nos diferentes contextos educacionais com a premência de ações interdisciplinares contra o bullying

Abstract: Ca2+uptake, transmembrane electrical potential (??m) and oxygen consumption were measured in isolated ventricular mitochondria of rats from 3 days to 5 months of age. Estimated values of ruthenium red-sensitive, succinate-supported maximal rate of Ca2+uptake (Vmax, expressed as nmol Ca2+/min/mg protein) were higher in neonates and gradually fell during postnatal development (from 435±24 at 3–6 days, to 156±10 in adults,P<0.001), whereas K0.5values (10µm) were not significantly affected by age. Under similar conditions, mitochondria from adults (5 months old) and neonates (4–6 days old) showed comparable state 4 (succinate anda-ketoglutarate as substrates) and state 3ADP(a-ketoglutarate-supported) respiration rates, as well as ??m values (-150 mV). Respiration-indpendent ??m and Ca2+uptake, supported by valinomycin-induced K+efflux were also investigated at these ages. A transient ??m (-30 mV) was evoked by valinomycin in both neonatal and adult mitochondria. Respiration-independent Ca2+uptake was also transient, but its initial rate was significantly higher in neonates than in adults (49.4±10.0v28.0±5.7 mmol Ca2+/min/mg protein,P<0.01). These results indicate that Ca2+uptake capacity of rat cardiac mitochondria is remarkably high just after birth and declines over the first weeks of postnatal life, without change in apparent affinity of the transporter. Increased mitochondrial Ca2+uptake rate in neonates appears to be related to the uniporter itself, rather than to modification of the driving force of the transport

Calcium dynamics is central in cardiac physiology, as the key event leading to the excitation-contraction coupling (ECC) and relaxation processes. The primary function of Ca2+ in the heart is the control of mechanical activity developed by the myofibril contractile apparatus. This key role of Ca2+ signaling explains the subtle and critical control of important events of ECC and relaxation, such as Ca2+ influx and SR Ca2+ release and uptake. The multifunctional Ca2+-calmodulin-dependent protein kinase II (CaMKII) is a signaling molecule that regulates a diverse array of proteins involved not only in ECC and relaxation but also in cell death, transcriptional activation of hypertrophy, inflammation, and arrhythmias. CaMKII activity is triggered by an increase in intracellular Ca2+ levels. This activity can be sustained, creating molecular memory after the decline in Ca2+ concentration, by autophosphorylation of the enzyme, as well as by oxidation, glycosylation, and nitrosylation at different sites of the regulatory domain of the kinase. CaMKII activity is enhanced in several cardiac diseases, altering the signaling pathways by which CaMKII regulates the different fundamental proteins involved in functional and transcriptional cardiac processes. Dysregulation of these pathways constitutes a central mechanism of various cardiac disease phenomena, like apoptosis and necrosis during ischemia/reperfusion injury, digitalis exposure, post-acidosis and heart failure arrhythmias, or cardiac hypertrophy. Here we summarize significant aspects of the molecular physiology of CaMKII and provide a conceptual framework for understanding the role of the CaMKII cascade on Ca2+ regulation and dysregulation in cardiac health and disease

Abstract: Atrial tachyarrhythmias (AT) are the most common cardiac rhythm disturbance. In the present study, we analyzed the cholinergic–adrenergic interaction in the in vitro induction of cholinergic-dependent tachyarrhythmia by high-frequency electric stimulation. Tachyarrhythmia was evoked in isolated rat right atria by trains of electric stimuli. Atrial response was expressed as the tachyarrhythmia induction index (ATI, i.e. the fraction of applied trains that resulted in arrhythmia induction). ATI was reversibly increased by 0.6 µM carbachol (CCh), which also decreased atrial spontaneous rate (ASR). In contrast, 10 nM isoproterenol (ISO), 100 µM tyramine and the phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX, 100 µM) increased ASR and decreased ATI. Amiodarone (AMI, 10 µM) reduced ATI in the presence and absence of CCh. Further CCh addition restored ATI in atria treated with either IBMX or AMI, but not when both compounds were present. Increase in ATI by CCh in atria pretreated with IBMX plus ISO was significantly attenuated by 3 mM NaF. The antagonism between cholinergic muscarinic and ß-adrenergic receptor stimulation (the former facilitating and the latter inhibiting tachyarrhythmia installation) possibly involves regulation of the phosphorylation status of adenosine cyclic 3'-5'-monophosphate (cAMP)-dependent protein kinase substrates. Additionally, cAMP-independent, AMI-sensitive mechanism stimulated by CCh (possibly muscarinic-dependent K+ current activation) seems to contribute to AT facilitation

Subtraction of ictal-interictal SPECT co-registered to MRI (SISCOM) is a quantification tool that can improve the sensitivity and specificity of the epileptogenic zone (EZ) localization. Commercially available image analysis software packages for SISCOM are costly, and Statistical Parametric Mapping (SPM) could be an alternative free software for the definition of the EZ. There are only a few studies that compare SISCOM using SPM (SISCOM-SPM) with visual analysis. To compare SISCOM-SPM vs. visual analysis for localization of the EZ in patients with pharmacoresistant focal epilepsies. We evaluated all our patients with focal epilepsies that underwent ictal and interictal SPECT. We defined the reference standard to locate the EZ by pathology and follow-up (in patients submitted to surgery), or seizure semiology, serial EEG, long-term video-EEG, 18F-FDG PET/CT, and MRI (in patients who were not operated). We compared the location of the EZ by visual analysis of SPECT images and by SISCOM-SPM to the reference standard and classified as concordant, discordant, or partially concordant. We included 23 patients. Visual analysis was concordant with the EZ reference standard in only 13 patients (56.5%), while SISCOM-SPM was concordant in 18 cases (78.3%), providing a 21.8% increase in the location of EZ. However, this difference was not significant due to the small sample size (p = 0.0856). Our preliminary results demonstrate that, in clinical practice, SISCOM-SPM has the potential to add information that might help localize the EZ compared to visual analysis. SISCOM-SPM has a lower cost than other commercially available SISCOM software packages, which is an advantage for developing countries. Studies with more patients are necessary to confirm our findings

Abstract: Electric field stimulation is widely used for heart pacing and arrhythmia reversion. In this study, we analysed the influence of waveform and direction of external stimulating electric field on the excitation threshold of isolated ventricular myocytes. The threshold field (ET) was lower when the field was applied longitudinally (ET,L) rather than transversally (ET,T) to the cell major axis. Rheobase was greater for transversal stimulation, but chronaxie and estimated membrane polarization were similar for both directions. The calculated maximal variation in membrane potential at the threshold (_VT ? 15 mV) was insensitive to field direction. As _VT values were similar, we assumed that the ET,T/ET,L ratio might be described solely as the ratio of the major and minor cell semi-axes. Accordingly, the ratio thus estimated was comparable to that determined experimentally. Stimulus waveform significantly affected both ET and _VT, which were greater for monophasic versus biphasic stimuli. Direction and waveform effects were independent. We conclude that (a) direction affects ET by its influence on the ability of a given field intensity to cause threshold membrane polarization and (b) thresholdlowering effects of longitudinal stimulation and biphasic waveforms apparently depend on different mechanisms, are additive and thus may be combined to decrease the energy requirement for myocardial stimulation

Abstract: Cardiac inotropy depends, among other factors, on the interval between contractions. In this study, we developed instrumentation for cell shortening recording, which was used to investigate the influence of stimulatory rhythm on contraction amplitude of isolated rat ventricular myocytes. Peak cell shortening amplitude was recorded during elec tric stimulation at the average rate of 0.5 Hz with different stimulatory patterns: regular and pseudo-random rhythms, as well as double pulse stimulation. Cells were perfused at 23 ºC with modified Tyrode’s solution with or without 10 nM isoproterenol (ISO). The main advantages of the developed microscopy system were its relatively low cost (~US$ 1,000.00), small size (150 × 170 × 300 mm), and absence of detectable optic distortions. We observed that average con traction amplitude was similar for all stimulatory patterns, in the absence and presence of ISO (p > 0.05), although the amplitude of individual contractions was highly dependent on the previous interval, and was significantly increased by ISO (p < 0.05). With the double pulse patterns, the am plitude ratio of contractions following the shorter and the longer intervals was ~0.55. ISO positive inotropic effect was more prominent for contractions after short intervals, which increased the ratio to ~0.80. This might be explained by ac celeration of the recovery of sarcoplasmic reticulum Ca2+ release channels from the adapted state, possibly by protein kinase A-dependent phosphorylation, which would result in enhanced systolic Ca2+ release

Abstract: Purpose: Quantifications in nuclear medicine are occasionally limited by the lack of standardization for defining volumes of interest (VOIs) on functional images. In the present article, we propose the use of computed tomography (CT)-based skeletal segmentation to determine anatomically the VOI in order to calculate quantitative parameters of fluorine 18 fluorodeoxyglucose (F-18-FDG) PET/CT images from patients with multiple myeloma. Methods: We evaluated 101 whole-body F-18-FDG PET/CTs of 58 patients with multiple myeloma. An initial subjective visual analysis of the PET images was used to classify the bone involvement as negative/mild, moderate, or marked. Then, a fully automated CT-based segmentation of the skeleton was performed on PET images. The maximum, mean, and SD of the standardized uptake values (SUVmax, SUVmean, and SDSUV) were calculated for bone tissue and compared with the visual analysis. Results: Forty-five (44.5%), 32 (31.7%), and 24 (23.8%) PET images were, respectively, classified as negative/mild, moderate, or marked bone involvement. All quantitative parameters were significantly related to the visual assessment of bone involvement. This association was stronger for the SUVmean [odds ratio (OR): 10.52 (95% confidence interval (CI), 5.68-19.48); P < 0.0001] and for the SDSUV [OR: 5.58 (95% CI, 3.31-9.42); P < 0.001) than for the SUVmax [OR: 1.01 (95% CI, 1.003-1.022); P = 0.003]. Conclusion: CT-based skeletal segmentation allows for automated and therefore reproducible calculation of PET quantitative parameters of bone involvement in patients with multiple myeloma. Using this method, the SUVmean and its respective SD correlated better with the visual analysis of F-18-FDG PET images than SUVmax. Its value in staging and evaluating therapy response needs to be evaluated

Quantifications in nuclear medicine are occasionally limited by the lack of standardization for defining volumes of interest (VOIs) on functional images. In the present article, we propose the use of computed tomography (CT)–based skeletal segmentation to determine anatomically the VOI in order to calculate quantitative parameters of fluorine 18 fluorodeoxyglucose (18F-FDG) PET/CT images from patients with multiple myeloma. We evaluated 101 whole-body 18F-FDG PET/CTs of 58 patients with multiple myeloma. An initial subjective visual analysis of the PET images was used to classify the bone involvement as negative/mild, moderate, or marked. Then, a fully automated CT–based segmentation of the skeleton was performed on PET images. The maximum, mean, and SD of the standardized uptake values (SUVmax, SUVmean, and SDSUV) were calculated for bone tissue and compared with the visual analysis. Forty-five (44.5%), 32 (31.7%), and 24 (23.8%) PET images were, respectively, classified as negative/mild, moderate, or marked bone involvement. All quantitative parameters were significantly related to the visual assessment of bone involvement. This association was stronger for the SUVmean [odds ratio (OR): 10.52 (95% confidence interval (CI), 5.68–19.48); P < 0.0001] and for the SDSUV [OR: 5.58 (95% CI, 3.31–9.42); P < 0.001) than for the SUVmax [OR: 1.01 (95% CI, 1.003–1.022); P = 0.003]. CT–based skeletal segmentation allows for automated and therefore reproducible calculation of PET quantitative parameters of bone involvement in patients with multiple myeloma. Using this method, the SUVmean and its respective SD correlated better with the visual analysis of 18F-FDG PET images than SUVmax. Its value in staging and evaluating therapy response needs to be evaluated

The relativ contributions of Ca2+ transporters to intracellular Ca2+ concentration ([Ca2+]i) decline associated with twitch relaxation were analyzed in intact ventricular myocytes from developing and adult rats. This was accomplished by estimation of individual integrated Ca2+fluxes with the use of kinetic parameters calculated from [Ca2+]i measurements during twitches and caffeine-evoked contractures, and from myocardial passive Ca2+ buffering data. Our main findings were the following:1) twitch relaxation and [Ca2+]idecline were significantly slower during the first postnatal week than in adults, 2) inhibition of sarcoplasmic reticulum (SR) Ca2+ accumulation resulted in faster [Ca2+]i decline in young cells than in adult cells, 3) the contributions of the SR Ca2+uptake and Na+/Ca2+ exchange (NCX) to twitch relaxation increased from ∼75 to 92%, and decreased from 24 to 5%, respectively, from birth to adulthood, and 4) Ca2+ transport by the sarcolemmal Ca2+-ATPase was apparently increased in neonates. Our data indicate that despite a marked increase in NCX contribution to cell relaxation in immature rats, the SR Ca2+-ATPase appears to be the predominant transporter responsible for relaxation-associated [Ca2+]i decline from birth to adulthood, considerable structural and functional changes take place in the mammalian ventricle after birth. The cell proliferation rate drops drastically while cells undergo marked differentiation and growth. In the rat, myocardial protein content is more than duplicated, the relative cell volume occupied by certain organelles [i.e., myofilaments, sarcoplasmic reticulum (SR), and mitochondria] is greatly increased, and the cell surface-to-volume ratio decreases at least two times within the first 2 postnatal weeks (10, 21, 28, 35,36). Development of the t-tubular system during this period (29) allows action potential conduction along more internal regions of the cell, thus compensating for increase in cell volume and permitting synchronous excitation of the cell as a whole. In the rat heart, expression of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2; both mRNA and protein levels), as well as Ca2+ uptake rates by SR vesicles, are reported to be low just after birth and to increase during postnatal development (17, 22, 35). In contrast, the Na+/Ca2+ exchanger (NCX) appears to undergo opposite developmental changes. Both mRNA and protein levels were found to be much higher in the neonatal heart than in the adult rat heart, with subsequent downregulation as maturation proceeds (11,35). Accordingly, the rate of Na+-dependent Ca2+ uptake by cardiac sarcolemmal vesicles from neonatal and young rats is considerably higher than in adults (35). Because SR Ca2+ uptake and Ca2+ extrusion via the NCX are the main pathways for [Ca2+]idecrease during relaxation of the adult mammalian ventricle (3,6, 27), it would be expected that these changes in SR Ca2+-ATPase (SR-ATPase) and NCX expression might result in major change in the individual contribution of each transporter to relaxation. That is, NCX, which is responsible for <10% of the Ca2+ transport during relaxation of adult rat myocytes (3, 27), would play a more prominent role in relaxation and might even equal or surpass the contribution of the SR Ca2+ uptake. Although marked ontogenetic changes in the relative roles of SR-ATPase and NCX in twitch relaxation might be expected from the available data on cell protein content and Ca2+ transport in subcellular preparations, it is difficult to predict the impact of these changes in the live cardiac cell. The importance of specific Ca2+transporters to relaxation-associated Ca2+ decline during postnatal development has been examined in only a few studies (2), and quantitative estimation of the relative contribution on these transporters is still lacking. Moreover, possible ontogenetic changes in transporters other than SR-ATPase and NCX have not been addressed so far. The purpose of the present study was to investigate the following:1) whether the relative participation of SR-ATPase and NCX in twitch relaxation of intact, isolated rat ventricular myocytes is actually altered during postnatal development, 2) the extent at which the contribution of each transporter is modified,3) the time course of these changes, and 4) possible developmental variation in the contribution of the mitochondrial Ca2+ uptake via the Ca2+uniporter (Mito-U) and sarcolemmal Ca2+-ATPase (SL-ATPase) to twitch relaxation. Our results indicate increased activity of SL-ATPase in preweaning rats (especially neonates), and much higher role of NCX in relaxation during the first postnatal week, compared with adults. However, the SR-ATPase is still the main transporter responsible for twitch relaxation, even in the neonatal rat ventricle

Abstract: To identify the factors that influenced the mental capacity to work of nursing technicians during the COVID-19 pandemic. A cross-sectional study, carried out at two reference hospitals in assisting the population during the COVID-19 pandemic. A total of 237 professionals from Intensive Care Units participated and answered a questionnaire. Multiple linear regression models were used to assess the correlation between mental capacity to work and variables related to risks of contamination, institutional support and health. Lack of COVID-19 tests, lack of knowledge of routine, absences in 2021 and mental illness contributed to worse mental capacity to work. Management embracement and physical capacity were considered protective factors. Reduced work capacity in relation to mental demands can affect professional performance and quality of care, with implications for patients and health institutions