Novel Mutation in the ATP-Binding Cassette Transporter A3 (ABCA3) Encoding Gene Causes Respiratory Distress Syndrome in A Term Newborn in Southwest Iran

Introduction: ABCA3 glycoprotein belongs to the ATP-binding cassette (ABC) superfamily of transporters, which utilize the energy derived from hydrolysis of ATP for the translocation of a wide variety of substrates across the plasma membrane. Mutations in the ABCA3 gene are knowingly causative for fatal surfactant deficiency, particularly respiratory distress syndrome (RDS) in term babies. Case Presentation: In this study, Sanger sequencing of the whole ABCA3 gene (NCBI NM_001089) was performed in a neonatal boy with severe RDS. A homozygous mutation has been identified in the patient. Parents were heterozygous for the same missense mutation GGA > AGA at position 202 in exon 6 of the ABCA3 gene (c.604G > A; p.G202R). Furthermore, 70 normal individuals have been analyzed for the mentioned change with negative results. Conclusions: Regarding Human Genome Mutation Database (HGMD) and other literature recherche, the detected change is a novel mutation and has not been reported before. Bioinformatics mutation predicting tools prefer it as pathogenic.

Characterization of the poxAB operon encoding a class D carbapenemase in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a dreaded opportunistic pathogen that causes severe and often intractable infections in immunocompromised and critically ill patients. This bacterium is also the primary cause of fatal lung infections in patients with cystic fibrosis and a leading nosocomial pathogen responsible for nearly 10% of all hospital-acquired infections. P. aeruginosa is intrinsically recalcitrant to most classes of antibiotics and has the ability to acquire additional resistance during treatment. In particular, resistance to the widely used β-lactam antibiotics is frequently mediated by the expression of AmpC, a chromosomally encoded β-lactamase that is ubiquitously found in P. aeruginosa strains. This dissertation delved into the role of a recently reported chromosomal β-lactamase in P. aeruginosa called PoxB. To date, no detailed studies have addressed the regulation of poxB expression and its contribution to β-lactam resistance in P. aeruginosa. In an effort to better understand the role of this β-lactamase, poxB was deleted from the chromosome and expressed in trans from an IPTG-inducible promoter. The loss of poxB did not affect susceptibility. However, expression in trans in the absence of ampC rendered strains more resistant to the carbapenem β-lactams. The carbapenem-hydrolyzing phenotype was enhanced, reaching intermediate and resistant clinical breakpoints, in the absence of the carbapenem-specific outer membrane porin OprD. As observed for most class D β-lactamases, PoxB was only weakly inhibited by the currently available β-lactamase inhibitors. Moreover, poxB was shown to form an operon with the upstream located poxA, whose expression in trans decreased pox promoter (Ppox) activity suggesting autoregulation. The transcriptional regulator AmpR negatively controlled Ppox activity, however no direct interaction could be demonstrated. A mariner transposon library identified genes involved in the transport of polyamines as potential regulators of pox expression. Unexpectedly, polyamines themselves were able induce resistance to carbapenems. In summary, P. aeruginosa carries a chromosomal-encoded β-lactamase PoxB that can provide resistance against the clinically relevant carbapenems despite its narrow spectrum of hydrolysis and whose activity in vivo may be regulated by polyamines.^

Effects of alcohol intoxication and encoding conditions on eyewitness memory

Several researchers have investigated the effects of alcohol on memory. Few researchers have studied the effects of alcohol on an eyewitness's recall and recognition of crime events. This study proposed to examine the effects of alcohol and viewing conditions on subjects' ability to recall information regarding a videotaped bank robbery. Thirty male and 22 female subjects participated in a 2 (consumption: alcohol v. no alcohol) x 2 (lighting: good v. poor) factorial experiment with Average Accuracy and Total Amount of Information recalled as the primary dependent measures. There was no significant difference between the Intoxicated and Sober subjects regarding the amount of information recalled or their average accuracy. The main effect for lighting conditions and gender differences were also not significant.

Proposta de Implementação do Balanced Scorecard numa Clínica Privada

O presente trabalho visa propor a implementação do Balanced Scorecard (BSC) numa clínica privada, procurando desenvolver um esboço de um scorecard, com as respetivas perspetivas, objetivos, metas, indicadores e iniciativas estratégicas. Concluímos que o BSC configura-se de grande utilidade para a gestão da Clínica, nomeadamente ao fornecer aos funcionários uma linha clara da visão organizacional e da forma como as suas funções estão ligadas aos objetivos globais da organização; ao definir prioridades; ao identificar, racionalizar e alinhar as diversas iniciativas; ao ligar a estratégia com a afetação dos recursos disponíveis e ao incentivar a aprendizagem e a melhoria.

Proposta de Implementação do Balanced Scorecard numa Clínica Privada

O presente trabalho visa propor a implementação do Balanced Scorecard (BSC) numa clínica privada, procurando desenvolver um esboço de um scorecard, com as respetivas perspetivas, objetivos, metas, indicadores e iniciativas estratégicas. Concluímos que o BSC configura-se de grande utilidade para a gestão da Clínica, nomeadamente ao fornecer aos funcionários uma linha clara da visão organizacional e da forma como as suas funções estão ligadas aos objetivos globais da organização; ao definir prioridades; ao identificar, racionalizar e alinhar as diversas iniciativas; ao ligar a estratégia com a afetação dos recursos disponíveis e ao incentivar a aprendizagem e a melhoria.

O Balanced Scorecard em entidades sem fins lucrativos: um estudo de caso

A presente dissertação aborda o Balanced Scorecard (BSC), uma ferramenta de gestão colocada em prática nos primeiros anos da década de 90, que tem como principal objetivo avaliar a performance das organizações, através de indicadores financeiros e não-financeiros, e possibilitar a gestão da estratégia, sendo uma das ferramentas mais difundidas nas organizações nos últimos anos. A dissertação pretende responder às questões sobre como o BSC pode ser aplicado numa organização sem fins lucrativos de pequena dimensão e de que forma pode trazer benefícios para a mesma. O objetivo foi desenvolver um modelo de BSC para uma organização sem fins lucrativos cuja atividade se centra no ensino do xadrez junto dos mais jovens. Desta forma, procura-se dotar a organização de uma ferramenta de gestão que permita medir o seu desempenho e o valor que acrescenta à sociedade e, ainda, delinear uma estratégia de longo prazo consistente e sustentável. Para a realização desta dissertação foi efetuado, numa primeira fase, um estudo exploratório, no qual se pretende obter informações relevantes sobre o objeto de estudo, através da revisão de literatura existente. Numa segunda fase foi realizado um estudo de caso que consiste numa proposta de aplicação do BSC na Academia de Xadrez de Barcelos, uma entidade sem fins lucrativos com dois anos de existência. Foram definidas a visão, missão, valores e estratégias da organização, seguindo-se a criação do mapa estratégico, com as respetivas perspetivas, relações de causa-efeito, objetivos, indicadores, metas e iniciativas. Concluímos que, apesar da maior limitação deste estudo ter sido o facto de se tratar de uma organização recente, encontrando-se ainda numa fase de organização interna, o BSC é uma ferramenta que permitirá definir a estratégia de uma forma mais clara e objetiva. A maior influência que a proposta de BSC exerceu sobre a organização foi a de fazer com que houvesse uma maior consciência da importância de uma organização interna que possibilite atingir os objetivos definidos e ainda definir iniciativas para atingir esses objetivos.

Análise da implementação do Balanced Scorecard no sistema SICREDI.

2011

Convergent bioenergetic defects in Coenzyme Q10 depleted cells by pharmacological inhibition of coq2 enzyme (p-hydroxybenzoate polyprenyl transferase) and by genome editing technology targeting the encoding gene (COQ2)

Primary CoQ10 deficiency diseases encompass a heterogeneous spectrum of clinical phenotypes. Among these, defect or mutation on COQ2 gene, encoding a para-hydroxybenzoate polyprenyl transferase, have been associated with different diseases. Understanding the functional and metabolic impact of COQ2 mutation and the consequent CoQ10 deficiency is still a matter of debate. To date the aetiology of the neurological phenotypes correlated to CoQ10 deficiency does not present a clear genotype-phenotype association. In addition to the metabolic alterations due to Coenzyme Q depletion, the impairment of mitochondrial function, associated with the reduced CoQ level, could play a significant role in the metabolic flexibility of cancer. This study aimed to characterize the effect of varying degrees of CoQ10 deficiency and investigate the multifaceted aspect of CoQ10 depletion and its impact on cell metabolism. To induced CoQ10 depletion, different cell models were used, employing a chemical and genome editing approach. In T67 and MCF-7 CoQ10 depletion was achieved by a competitive inhibitor of the enzyme, 4-nitrobenzoate (4-NB), whereas in SH-SY5Y the COQ2 gene was edited via CRISPR-Cas9 cutting edge technology.

Prevention of binge drinking in young adolescents through the promotion of a balanced level of psychological well-being: be-dry

This doctoral thesis presents a project carried out in secondary schools located in the city of Ferrara with the primary objective of demonstrating the effectiveness of an intervention based on Well-Being Therapy (Fava, 2016) in reducing alcohol use and improving lifestyles. In the first part (chapters 1-3), an introduction on risky behaviors and unhealthy lifestyle in adolescence is presented, followed by an examination of the phenomenon of binge drinking and of the concept of psychological well-being. In the second part (chapters 4-6), the experimental study is presented. A three-arm cluster randomized controlled trial including three test periods was implemented. The study involved eleven classes that were randomly assigned to receive well-being intervention (WBI), lifestyle intervention (LI) or not receive intervention (NI). Results were analyzed by linear mixed model and mixed-effects logistic regression with the aim to test the efficacy of WBI in comparison with LI and NI. AUDIT-C total score increased more in NI in comparison with WBI (p=0.008) and LI (p=0.003) at 6-month. The odds to be classified as at-risk drinker was lower in WBI (OR 0.01; 95%CI 0.01–0.14) and LI (OR 0.01; 95%CI 0.01–0.03) than NI at 6-month. The odds to use e-cigarettes at 6-month (OR 0.01; 95%CI 0.01–0.35) and cannabis at post-test (OR 0.01; 95%CI 0.01–0.18) were less in WBI than NI. Sleep hours at night decreased more in NI than in WBI (p = 0.029) and LI (p = 0.006) at 6-month. Internet addiction scores decreased more in WBI (p = 0.003) and LI (p = 0.004) at post-test in comparison with NI. Conclusions about the obtained results, limitations of the study, and future implications are discussed. In the seventh chapter, the data of the project collected during the pandemic are presented and compared with those from recent literature.

Uncovering the encoding and transmission of behaviourally relevant information in neural activity

Most cognitive functions require the encoding and routing of information across distributed networks of brain regions. Information propagation is typically attributed to physical connections existing between brain regions, and contributes to the formation of spatially correlated activity patterns, known as functional connectivity. While structural connectivity provides the anatomical foundation for neural interactions, the exact manner in which it shapes functional connectivity is complex and not yet fully understood. Additionally, traditional measures of directed functional connectivity only capture the overall correlation between neural activity, and provide no insight on the content of transmitted information, limiting their ability in understanding neural computations underlying the distributed processing of behaviorally-relevant variables. In this work, we first study the relationship between structural and functional connectivity in simulated recurrent spiking neural networks with spike timing dependent plasticity. We use established measures of time-lagged correlation and overall information propagation to infer the temporal evolution of synaptic weights, showing that measures of dynamic functional connectivity can be used to reliably reconstruct the evolution of structural properties of the network. Then, we extend current methods of directed causal communication between brain areas, by deriving an information-theoretic measure of Feature-specific Information Transfer (FIT) quantifying the amount, content and direction of information flow. We test FIT on simulated data, showing its key properties and advantages over traditional measures of overall propagated information. We show applications of FIT to several neural datasets obtained with different recording methods (magneto and electro-encephalography, spiking activity, local field potentials) during various cognitive functions, ranging from sensory perception to decision making and motor learning. Overall, these analyses demonstrate the ability of FIT to advance the investigation of communication between brain regions, uncovering the previously unaddressed content of directed information flow.

Two-component System Vicrk Regulates Functions Associated With Establishment Of Streptococcus Sanguinis In Biofilms.

Streptococcus sanguinis is a commensal pioneer colonizer of teeth and an opportunistic pathogen of infectious endocarditis. The establishment of S. sanguinis in host sites likely requires dynamic fitting of the cell wall in response to local stimuli. In this study, we investigated the two-component system (TCS) VicRK in S. sanguinis (VicRKSs), which regulates genes of cell wall biogenesis, biofilm formation, and virulence in opportunistic pathogens. A vicK knockout mutant obtained from strain SK36 (SKvic) showed slight reductions in aerobic growth and resistance to oxidative stress but an impaired ability to form biofilms, a phenotype restored in the complemented mutant. The biofilm-defective phenotype was associated with reduced amounts of extracellular DNA during aerobic growth, with reduced production of H2O2, a metabolic product associated with DNA release, and with inhibitory capacity of S. sanguinis competitor species. No changes in autolysis or cell surface hydrophobicity were detected in SKvic. Reverse transcription-quantitative PCR (RT-qPCR), electrophoretic mobility shift assays (EMSA), and promoter sequence analyses revealed that VicR directly regulates genes encoding murein hydrolases (SSA_0094, cwdP, and gbpB) and spxB, which encodes pyruvate oxidase for H2O2 production. Genes previously associated with spxB expression (spxR, ccpA, ackA, and tpK) were not transcriptionally affected in SKvic. RT-qPCR analyses of S. sanguinis biofilm cells further showed upregulation of VicRK targets (spxB, gbpB, and SSA_0094) and other genes for biofilm formation (gtfP and comE) compared to expression in planktonic cells. This study provides evidence that VicRKSs regulates functions crucial for S. sanguinis establishment in biofilms and identifies novel VicRK targets potentially involved in hydrolytic activities of the cell wall required for these functions.

Reduced Plasma Angiotensin Ii Levels Are Reversed By Hydroxyurea Treatment In Mice With Sickle Cell Disease.

Sickle cell disease (SCD) pathogenesis leads to recurrent vaso-occlusive and hemolytic processes, causing numerous clinical complications including renal damage. As vasoconstrictive mechanisms may be enhanced in SCD, due to endothelial dysfunction and vasoactive protein production, we aimed to determine whether the expression of proteins of the renin-angiotensin system (RAS) may be altered in an animal model of SCD. Plasma angiotensin II (Ang II) was measured in C57BL/6 (WT) mice and mice with SCD by ELISA, while quantitative PCR was used to compare the expressions of the genes encoding the angiotensin-II-receptors 1 and 2 (AT1R and AT2R) and the angiotensin-converting enzymes (ACE1 and ACE2) in the kidneys, hearts, livers and brains of mice. The effects of hydroxyurea (HU; 50-75mg/kg/day, 4weeks) treatment on these parameters were also determined. Plasma Ang II was significantly diminished in SCD mice, compared with WT mice, in association with decreased AT1R and ACE1 expressions in SCD mice kidneys. Treatment of SCD mice with HU reduced leukocyte and platelet counts and increased plasma Ang II to levels similar to those of WT mice. HU also increased AT1R and ACE2 gene expression in the kidney and heart. Results indicate an imbalanced RAS in an SCD mouse model; HU therapy may be able to restore some RAS parameters in these mice. Further investigations regarding Ang II production and the RAS in human SCD may be warranted, as such changes may reflect or contribute to renal damage and alterations in blood pressure.

Dietary Supplement Usage And Motivation In Brazilian Road Runners.

The consumption of dietary supplements is highest among athletes and it can represent potential a health risk for consumers. The aim of this study was to determine the prevalence of consumption of dietary supplements by road runners. We interviewed 817 volunteers from four road races in the Brazilian running calendar. The sample consisted of 671 male and 146 female runners with a mean age of 37.9 ± 12.4 years. Of the sample, 28.33% reported having used some type of dietary supplement. The main motivation for this consumption is to increase in stamina and improve performance. The probability of consuming dietary supplements increased 4.67 times when the runners were guided by coaches. The consumption of supplements was strongly correlated (r = 0.97) with weekly running distance, and also highly correlated (r = 0.86) with the number of years the sport had been practiced. The longer the runner had practiced the sport, the higher the training volume and the greater the intake of supplements. The five most frequently cited reasons for consumption were: energy enhancement (29.5%), performance improvement (17.1%), increased level of endurance (10.3%), nutrient replacement (11.1%), and avoidance of fatigue (10.3%). About 30% of the consumers declared more than one reason for taking dietary supplements. The most consumed supplements were: carbohydrates (52.17%), vitamins (28.70%), and proteins (13.48%). Supplement consumption by road runners in Brazil appeared to be guided by the energy boosting properties of the supplement, the influence of coaches, and the experience of the user. The amount of supplement intake seemed to be lower among road runners than for athletes of other sports. We recommend that coaches and nutritionists emphasise that a balanced diet can meet the needs of physically active people.

Obesogenic Environment By Excess Of Dietary Fats In Different Phases Of Development Reduces Spermatic Efficiency Of Wistar Rats At Adulthood: Correlations With Metabolic Status.

This study compares the impact of obesogenic environment (OE) in six different periods of development on sperm parameters and the testicular structure of adult rats and their correlations with sex steroid and metabolic scenario. Wistar rats were exposed to OE during gestation (O1), during gestation/lactation (O2), from weaning to adulthood (O3), from lactation to adulthood (O4), from gestation to sexual maturity (O5), and after sexual maturation (O6). OE was induced by a 20% fat diet, and control groups were fed a balanced diet (4% fat). Serum leptin levels and adiposity index indicate that all groups were obese, except for O1. Three progressive levels of impaired metabolic status were observed: O1 presented insulin resistance, O2 were insulin resistant and obese, and groups O3, O4, and O5 were insulin resistant, obese, and diabetic. These three levels of metabolic damage were proportional to the increase of leptin and decreased circulating testosterone. The impairment in the daily sperm production (DSP) paralleled these three levels of metabolic and hormonal damage being marginal in O1, increasing in O2, and being higher in groups O3, O4, O5, and O6. None of the OE periods affected the sperm transit time in the epididymis, and the lower sperm reserves were caused mainly by impaired DSP. In conclusion, OE during sexual maturation markedly reduces the DSP at adulthood in the rat. A severe reduction in the DSP also occurs in OE exposure during gestation/lactation but not in gestation, indicating that breast-feeding is a critical period for spermatogenic impairment under obesogenic conditions.

Semi-determinate Growth Habit Adjusts The Vegetative-to-reproductive Balance And Increases Productivity And Water-use Efficiency In Tomato (solanum Lycopersicum).

Tomato (Solanum lycopersicum) shows three growth habits: determinate, indeterminate and semi-determinate. These are controlled mainly by allelic variation in the SELF-PRUNING (SP) gene family, which also includes the florigen gene SINGLE FLOWER TRUSS (SFT). Determinate cultivars have synchronized flower and fruit production, which allows mechanical harvesting in the tomato processing industry, whereas indeterminate ones have more vegetative growth with continuous flower and fruit formation, being thus preferred for fresh market tomato production. The semi-determinate growth habit is poorly understood, although there are indications that it combines advantages of determinate and indeterminate growth. Here, we used near-isogenic lines (NILs) in the cultivar Micro-Tom (MT) with different growth habit to characterize semi-determinate growth and to determine its impact on developmental and productivity traits. We show that semi-determinate genotypes are equivalent to determinate ones with extended vegetative growth, which in turn impacts shoot height, number of leaves and either stem diameter or internode length. Semi-determinate plants also tend to increase the highly relevant agronomic parameter Brix×ripe yield (BRY). Water-use efficiency (WUE), evaluated either directly as dry mass produced per amount of water transpired or indirectly through C isotope discrimination, was higher in semi-determinate genotypes. We also provide evidence that the increases in BRY in semi-determinate genotypes are a consequence of an improved balance between vegetative and reproductive growth, a mechanism analogous to the conversion of the overly vegetative tall cereal varieties into well-balanced semi-dwarf ones used in the Green Revolution.