Assessing the impact of COVID-19 on the efficiency of Portuguese state-owned enterprise hospitals.

This paper uses Value-Based Data Envelopment Analysis (VBDEA), to assess the impact of the COVID-19 pandemic on the efficiency of 37 state-owned enterprises (SOE) hospitals by employing data publicly available from the Portuguese Health Service database between January and November 2019 and 2020, respectively. Furthermore, a productivity index (specifically adjusted to the VBDEA approach) is also used that allows identifying which factors are behind the relative efficiency changes of these hospitals. The factors considered to perform the efficiency assessment of the Portuguese SOE hospitals include labour, capacity, and activity-related indicators. Out of the 37 SOE hospitals, 21 and 17 were efficient in 2019 and 2020, respectively. Irrespective of the value functions considered, the hospitals more often viewed as a reference for best practices were Santa Maria Maior, Tâmega e Sousa and Entre Douro e Vouga. Santa Maria Maior and Algarve were the only hospitals found to be robustly efficient for both years. Overall, the majority of SOE hospitals showed negative productivity (except for Évora and Santa Maria Maior) and all of them presented negative technological change, thus highlighting the massive impact that the COVID-19 outbreak has had on the performance of these hospitals. An additional conclusion is that inefficient hospitals substantially increased all their resources in 2020 as compared to inefficient hospitals in 2019, suggesting that the inefficiency of these hospitals was not due to the lack of resources. Finally, irrespective of the model employed, the hospitals located in the Portuguese northern region were more resilient to the COVID-19 crisis. All in all, to become more resilient (even for future COVID-19 outbreaks), hospitals should undertake changes that are advantageous irrespective of the obstacles they face and that are even beneficial during normal times. A culture of cooperation within and across hospitals should also be cultivated, which allows exchanging resources where they can be used more efficiently.

Relationship between dental and periodontal health status and the salivary microbiome: bacterial diversity, co-occurrence networks and predictive models.

The present study used 16S rRNA gene amplicon sequencing to assess the impact on salivary microbiome of different grades of dental and periodontal disease and the combination of both (hereinafter referred to as oral disease), in terms of bacterial diversity, co-occurrence network patterns and predictive models. Our scale of overall oral health was used to produce a convenience sample of 81 patients from 270 who were initially recruited. Saliva samples were collected from each participant. Sequencing was performed in Illumina MiSeq with 2 × 300 bp reads, while the raw reads were processed according to the Mothur pipeline. The statistical analysis of the 16S rDNA sequencing data at the species level was conducted using the phyloseq, DESeq2, Microbiome, SpiecEasi, igraph, MixOmics packages. The simultaneous presence of dental and periodontal pathology has a potentiating effect on the richness and diversity of the salivary microbiota. The structure of the bacterial community in oral health differs from that present in dental, periodontal or oral disease, especially in high grades. Supragingival dental parameters influence the microbiota's abundance more than subgingival periodontal parameters, with the former making a greater contribution to the impact that oral health has on the salivary microbiome. The possible keystone OTUs are different in the oral health and disease, and even these vary between dental and periodontal disease: half of them belongs to the core microbiome and are independent of the abundance parameters. The salivary microbiome, involving a considerable number of OTUs, shows an excellent discriminatory potential for distinguishing different grades of dental, periodontal or oral disease; considering the number of predictive OTUs, the best model is that which predicts the combined dental and periodontal status.

Performance of SLEDAI-2K to detect a clinically meaningful change in SLE disease activity: a 36-month prospective cohort study of 334 patients.

OBJECTIVE: The objective of this paper is to evaluate the performance of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) in detecting clinically meaningful changes in SLE disease activity. METHODS: A longitudinal cohort study was conducted of 334 SLE patients during a 36-month follow-up. At each outpatient visit, disease activity was scored using the Physician Global Assessment (PGA) and SLEDAI-2K. Correlations between PGA and SLEDAI-2K were assessed. A clinically meaningful change in SLE disease activity was defined as a ΔPGA ≥ 0.3 points from baseline. Performance of SLEDAI-2K in detecting a clinically meaningful worsening or improvement was tested using receiver operating characteristic (ROC) analysis. RESULTS: Adjusted mean PGA and SLEDAI-2K scores presented a high correlation (rho = 0.824, p < 0.0005). In ROC analysis, a SLEDAI-2K variation presented an area under the curve (AUC) of 0.697 (95% confidence interval (CI) (0.628-0.766), p < 0.0005) to detect a clinically meaningful improvement, with a sensitivity of 28.8% for a SLEDAI-2K ≥ 4 reduction. The AUC to detect a clinically meaningful worsening was 0.877 (95% CI (0.822-0.932), p < 0.0005), with a sensitivity of 35.3%. CONCLUSIONS: SLEDAI-2K has a limited ability to detect clinically meaningful changes in SLE disease activity, failing to identify almost two-thirds of cases judged as having a clinically meaningful improvement or worsening. There is a need for more sensitive SLE disease activity measures in clinical practice and research.

Demonstration of Single-Barium-Ion Sensitivity for Neutrinoless Double-Beta Decay Using Single-Molecule Fluorescence Imaging.

A new method to tag the barium daughter in the double-beta decay of ^{136}Xe is reported. Using the technique of single molecule fluorescent imaging (SMFI), individual barium dication (Ba^{++}) resolution at a transparent scanning surface is demonstrated. A single-step photobleach confirms the single ion interpretation. Individual ions are localized with superresolution (∼2 nm), and detected with a statistical significance of 12.9σ over backgrounds. This lays the foundation for a new and potentially background-free neutrinoless double-beta decay technology, based on SMFI coupled to high pressure xenon gas time projection chambers.

Establishment and cryptic transmission of Zika virus in Brazil and the Americas.

Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

Accuracy of ultrasound in the diagnosis of acute cholecystitis with coexistent acute pancreatitis.

PURPOSE: Acute cholecystitis and pancreatitis are acute forms of cholecystolithiasis. The presence of acute cholecystitis can lead to important changes in therapy in the early course of acute pancreatitis. The aim of this study was to identify the accuracy of ultrasonography in diagnosing acute cholecystitis with coexistent acute pancreatitis. METHODS: Subjects were all those patients admitted to our hospital with a diagnosis of acute pancreatitis between 1998 and 2015 who underwent cholecystectomy within 15 days of the ultrasonography performed on admittance. Patient data were analyzed retrospectively to compare the ultrasound findings with the pathological findings of the resected gallbladders. Patients were allocated to two groups according to the signs of acute cholecystitis on ultrasonography: group 1 negative and group 2 positive. RESULTS: One hundred and twenty patients were enrolled in the study: 77 in group 1 and 43 in group 2. Similar results were found for the two groups with respect to the pathological diagnosis of acute cholecystitis, i.e., 31.2 % for group 1 and 27.9 % for group 2. Analysis indicated that there was no correlation between the ultrasonography data and pathological findings (p = 0.708). CONCLUSIONS: On the basis of our study, ultrasound findings alone cannot be used to accurately diagnose acute cholecystitis in the setting of acute pancreatitis.

Prevalência de cefaleia em uma unidade de diálise / Prevalence of headache in a dialysis clinic

Introdução: De acordo com a Sociedade Internacional de Cefaleia, a cefaleia é uma dor localizada acima da linha orbitomeatal, classificada como primária e secundária. A cefaleia da diálise consiste em uma dor de cabeça inespecífica que ocorre no período da diálise, podendo persistir após o término da sessão. Apesar de ser um sintoma comum em pacientes submetidos à hemodiálise, a cefaleia decorrente da terapia dialítica é pobremente estudada. Não se tem a sua etiologia precisa, porém infere-se que a gênese da cefaleia seja multifatorial. Objetivo: Avaliar a prevalência da cefaleia em pacientes submetidos à hemodiálise. Além disso, classificar as cefaleias apresentadas pelos pacientes estudados, inclusive as que não são decorrentes da diálise. Métodos: Trata-se de um estudo constituído por pacientes submetidos à terapia dialítica em uma clínica, de uma cidade brasileira, no período de maio a agosto de 2014. Este foi composto por 152 pacientes. Resultados: Foram analisados 77 (50,7%) pacientes do sexo masculino e 75 (49,3%) do sexo feminino. Dos 61 pacientes (40,1%) que afirmaram apresentar episódios de cefaleia, os tipos mais prevalentes foram cefaleia do tipo tensional ­ CTT (41%) e cefaleia da diálise (37,7%), sendo outros tipos menos frequentes. Ou seja, 23 (15,1%) dos 152 pacientes foram diagnosticados com cefaleia da diálise, isolada ou associada a outros tipos de cefaleia. Conclusão: Diante da elevada prevalência de tal condição, elaborar planos de ação para melhoria da qualidade de vida desses pacientes é uma medida relevante.

Introduction: According to the International Society of Headache, headache is a pain located above the orbitomeatal line, classified as primary and secondary. The dialysis headache isclassified as secondary and consists of a nonspecific headache that occurs during the period of dialysis and may persist after the end of the session. Despite being a common symptom in patients undergoing hemodialysis, headache resulting from dialysis is poorly studied. It does not have a precise etiology, however it appears that the genesis of the headache is multifactorial. Background. Evaluate the prevalence of headache in patients submitted to hemodialysis. Besides classify headaches evidenced by patient studied, including those which are not decurrent from dialysis. Methods. It´s a study consists of patients who had dialysis performed at a clinic, in a brazilian city, from May to August, 2014. This was composed of 152 patients. Results. 77 (50,7%) patients were males and 75 (49,3%) were females. Of the 61 (40,1%) affirmed evince headache episodes, the most prevalence types were tension type headache ­ CTT (41%) and headache from dialysis (37,7%), and other less common types. So, 23 (15,1%) of 152 patients were diagnosed with headache from dialysis, irrespective of being or not being associated with other types of headache. Conclusion. Such high prevalence of this condition, draw up action plans to improve the quality of life of these patients is a relevant measure.

2016 update of the Portuguese recommendations for the use of biological therapies in children and adolescents with Juvenile Idiopathic Arthritis.

OBJECTIVE: To provide evidence-based guidance for the rational and safe prescription of biological therapies in children and adolescents with juvenile idiopathic arthritis (JIAs) considering the latest available evidence and the new licensed biologics. METHODS: Rheumatologists and Pediatricians with expertise in Pediatric Rheumatology updated the recommendations endorsed by the Portuguese Society of Rheumatology and the Portuguese Society of Pediatrics based on published evidence and expert opinion. The level of agreement with final propositions was voted using an online survey. RESULTS: In total, 20 recommendations to guide the use of biological therapy in children and adolescents with JIAs are issued, comprising 4 general principles and 16 specific recommendations. A consensus was achieved regarding the eligibility and response criteria, maintenance of biological therapy, and procedures in case of non-response, for each JIA category. Specific recommendations concerning safety procedures were also updated. CONCLUSIONS: These recommendations take into account the specificities of each JIA category and are intended to continuously improve the management of JIA patients.

The future water environment--using scenarios to explore the significant water management challenges in England and Wales to 2050.

Society gets numerous benefits from the water environment. It is crucial to ensure that water management practices deliver these benefits over the long-term in a sustainable and cost-effective way. Currently, hydromorphological alterations and nutrient enrichment pose the greatest challenges in European water bodies. The rapidly changing climatic and socio-economic boundary conditions pose further challenges to water management decisions and the achievement of policy goals. Scenarios are a strategic tool useful in conducting systematic investigations of future uncertainties pertaining to water management. In this study, the use of scenarios revealed water management challenges for England and Wales to 2050. A set of existing scenarios relevant to river basin management were elaborated through stakeholder workshops and interviews, relying on expert knowledge to identify drivers of change, their interdependencies, and influence on system dynamics. In a set of four plausible alternative futures, the causal chain from driving forces through pressures to states, impacts and responses (DPSIR framework) was explored. The findings suggest that scenarios driven by short-term economic growth and competitiveness undermine current environmental legislative requirements and exacerbate the negative impacts of climate change, producing a general deterioration of water quality and physical habitats, as well as reduced water availability with adverse implications for the environment, society and economy. Conversely, there are substantial environmental improvements under the scenarios characterised by long-term sustainability, though achieving currently desired environmental outcomes still poses challenges. The impacts vary across contrasting generic catchment types that exhibit distinct future water management challenges. The findings suggest the need to address hydromorphological alterations, nutrient enrichment and nitrates in drinking water, which are all likely to be exacerbated in the future. Future-proofing river basin management measures that deal with these challenges is crucial moving forward. The use of scenarios to future-proof strategy, policy and delivery mechanisms is discussed to inform next steps.

Combined C4d and CD3 immunostaining predicts immunoglobulin (Ig)A nephropathy progression.

A number of molecules have been shown recently to be involved in the pathogenesis and progression of immunoglobulin (Ig)A nephropathy (IgAN). Among these, we have selected C4d (complement lectin pathway involvement), CD3 (T cell marker, traducing interstitial inflammation), transglutaminase 2 (TGase-2, involved in tissue fibrosis development) and p-extracelluar-regulated kinase (ERK)1/2 (protein kinase intracellular signaling molecule) to perform a panel of immunohistological biomarkers and assess its predictive value for disease progression. Immunohistochemical staining of these biomarkers was performed in paraffin sections from 74 renal biopsy cases with the clinical diagnosis of IgAN. Association between score analysis of these parameters and disease course was assessed through univariate and multivariate analysis, including baseline clinical and histological data. Univariate analysis showed that glomerular C4d, tubulointerstitial TGase2 and CD3 scores were associated with baseline proteinuria and disease progression. Multivariate analysis showed that only baseline estimated glomerular filtration rate (eGFR), C4d and CD3 were associated independently with progressive kidney disease (decline of at least 50% in the eGFR or progression to end-stage renal disease (ESRD) during the follow-up period). Establishing an accurate prediction model for IgAN progression is still a matter of research in clinical nephrology. The complement system, particularly lectin pathway activation, and T cell activation, have been shown previously to be potential modifiers of the disease course. Here we show that the combination of two histological biomarkers (C4d and CD3) can be a powerful predictor of IgAN progression and a potential useful tool for the clinical approach of this disease.

In vitro and in vivo evaluation of electrospun nanofibers of PCL, chitosan and gelatin: a comparative study.

Many polymers have been investigated with respect to their use in skin tissue engineering. However, directly comparable data on the role played by different polymers in assisting skin wound healing requires their in vitro and in vivo evaluation under the same conditions. Therefore, we performed a study in order to compare the performance of electrospun nanofiber mats from three different polymers concerning cell-scaffold interaction and wound healing promotion. A polyester (polycaprolactone, PCL), a protein (gelatin from cold water fish skin, GEL) and a polysaccharide (chitosan, CS) were the polymers chosen. Gelatin nanofibers were crosslinked with glutaraldehyde vapor. The scaffolds were characterized physico-chemically, in vitro by seeding with human fetal fibroblasts, HFFF2, and used in vivo as skin substitutes in a rat wound model with total skin removal. In vitro tests revealed that cells adhered and proliferated in all scaffolds. However, cells deep into the scaffold were only observed in the PCL and CS scaffolds. In in vivo tests CS scaffolds had the highest impact on the healing process by decreasing the extent of wound contraction and enhancing the production of a neodermis and re-epithelialization of the wound.

Cariogenic bacteria and dental health status in adolescents: the role of oral health behaviours.

AIM: To evaluate the association between dental health status and levels of cariogenic bacteria in teenagers and the influence of behaviours and socio-demographic background on levels of bacteria. MATERIALS AND METHODS: Study design: A cross-sectional population-based sample of 13-year-old adolescents (112 females and 78 males, total 190) was examined. The number of decayed, missing and filled surfaces (DMFS), plaque and hygiene index were recorded according to the WHO criteria. The saliva samples were collected in a sterile container and then analysed by culture on Mitis Salivarius Bacitracin (MSB) agar for mutans Streptococci and on Man Rogosa Sharp (MRS) agar for Lactobacilli. The levels of bacteria were expressed as the number of colonies forming units per millilitre of saliva (CFU/ml). Associations between levels of mutans Streptococci and Lactobacilli and dental health were estimated by odds ratio (OR) and 95% confidence interval (95% CI) using unconditional logistic regression. RESULTS: No mutans Streptococci were detected in 53.2% of the adolescents but 22.6% presented ≥ 10³ CFU/ml. For Lactobacilli, these values were, respectively 43.7% and 34.7%. After adjustment for gender and social class, the OR (95% CI) for DMFS >5 was 8.66 (3.57-21.02) if mutans Streptococci ≥ 10³ CFU and 2.11 (0.96-4.64) if Lactobacilli ≥ 10³ CFU. CONCLUSION: This data allow us to conclude that hygiene habits and dental visits are not associated with high levels of cariogenic bacteria, but high scores of DMFS were found in adolescents with high levels of mutans Streptococci and lower parents' education.

Pharmacogenetics role in the safety of acenocoumarol therapy.

Vitamin K antagonists (VKAs) remain as the most prescribed drug for treatment and prevention of thrombotic disorders in many countries, despite the recent approval of the new oral anticoagulants (NOACs). Although effectiveness and safety of VKAs are tightly associated to maintaining the patient within the international normalised ratio (INR) therapeutic range (TWR), they have been likened to NOACs when patients are in good INR control (≥66% of TWR). Therefore, assessing the safety of patients should be a priority in the selection of the anticoagulation therapy. The aim of this study was to evaluate the association between CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2*3, ABCB1 C3435T, APOE, CYP2C19*2 and CYP2C19*17 gene polymorphisms and treatment safety in 128 patients diagnosed with atrial fibrillation or venous thromboembolism during the initial first seven months of acenocoumarol therapy. After the first month, VKORC1-T-allele and APOE-E3/E3 genotype were independently associated to higher time above therapeutic range (TAR) and lower time below the therapeutic range (TBR). After seven months, VKORC1 T-allele predicted higher TAR, and was also associated to increased INR>4, particularly the TT-genotype (odds ratio [OR]: 32; 95% confidence interval [CI95%]: 6-175; p=810⁻5). C-alleles for CYP2C9*3 (OR: 5.5; CI95%: 1.8-17; p=0.003) and ABCB1 (OR: 8.9;CI95%: 1.1-70; p=0.039) independently influenced on INR>6 . Patients VKORC1-TT/ABCB1-C remained 26.8% [19.7-38.9] TAR, with associated relative risk (RR) for INR>4 1.8 higher (CI95%: 1.2-2.5; p=0.015). Patients VKORC1-TT also presented the highest risk of bleeding events (RR: 3.5;CI95%: 1.4-8.4; p=0,010). In conclusion, VKORC1, CYP2C9*3, APOE and ABCB1 genotypes should be considered in prevention of overanticoagulation and bleeding events in the initiation of acenocoumarol therapy.

In vitro evaluation of crosslinked electrospun fish gelatin scaffolds.

Gelatin from cold water fish skin was electrospun, crosslinked and investigated as a substrate for the adhesion and proliferation of cells. Gelatin was first dissolved in either water or concentrated acetic acid and both solutions were successfully electrospun. Cross-linking was achieved via three different routes: glutaraldehyde vapor, genipin and dehydrothermal treatment. Solution's properties (surface tension, electrical conductivity and viscosity) and scaffold's properties (chemical bonds, weight loss and fiber diameters) were measured. Cellular viability was analyzed culturing 3T3 fibroblasts plated on the scaffolds and grown up to 7 days. The cells were fixed and observed with SEM or stained for DNA and F-actin and observed with confocal microscopy. In all scaffolds, the cells attached and spread with varying degrees. The evaluation of cell viability showed proliferation of cells until confluence in scaffolds crosslinked by glutaraldehyde and genipin; however the rate of growth in genipin crosslinked scaffolds was slow, recovering only by day five. The results using the dehydrothermal treatment were the less satisfactory. Our results show that glutaraldehyde treated fish gelatin is the most suitable substrate, of the three studied, for fibroblast adhesion and proliferation.

Living versus cadaveric-donor renal transplant recipients: a comparison on sexual function.

Erectile dysfunction is experienced by 50% of men with end-stage renal disease (ESRD) and uremia. The origin of this dysfunction is multifactorial. The aim of this study was to compare living donor versus cadaveric donor transplant recipients regarding male sexual function. Seventy-seven sexually active male kidney transplant recipients (44 from living donors; 33 from cadaveric donors) were randomly selected from our single-center prospective database of 2016 renal transplants. Epidemiological and clinical data were collected between June 2010 and June 2011. Male sexual function was evaluated with the International Index of Erectile Function questionnaire (IIEF-15). We assessed the prevalence of male sexual dysfunction according to established cutoff points for each of the IIEF-15 domains. Mann-Whitney and Pearson's chi- square statistical tests were used to compare continuous and categorical variables, respectively. The median age at the time of completion of the questionnaires was 43 and 51 years (P = .003) with median times from transplantation was of 36 and 42 months for living donor and cadaveric donor recipients, respectively (P = .31). Median durations of ESRD before surgery were 17.5 and 57 months for living donor and cadaveric donor recipients, respectively (P < .001). Living donor and cadaveric donor recipients had median creatinine clearance values of 55 and 57 mL/min, respectively (P = .44). Median time after renal transplantation for first sexual intercourse was 1 and 2 months for living donor and cadaveric donor recipients, respectively (P = .35). Median body mass indices for living donor and cadaveric donor recipients were 24.8 and 24, respectively (P = .31). Regarding sexual function domains, there were significant differences only for intercourse satisfaction. In our cohort, living donor recipients tended to be younger, have shorter time of ESRD, and less incidence of hypertension or diabetes mellitus but with greater tobacco use. In conclusion, living donor transplantation exerted a favorable impact on sexual function.

First-trimester Down syndrome screening: pregnant women's knowledge.

OBJECTIVES: The primary aim of this study was to assess pregnant women's knowledge of first-trimester combined Down syndrome screening in a setting of required informed consent. As the secondary aim, we wanted to identify relevant differences in knowledge level among subgroups of pregnant women, including those informed in different ways about prenatal examinations. METHODS: Data stem from a population-based cross-sectional questionnaire study including 15 multiple-choice questions assessing knowledge of different aspects of screening. Included were 6427 first-trimester pregnant women from three Danish obstetric departments offering prenatal screening free of charge. Both participants and non-participants in the screening program were included. The results are based on 4095 responders (64%). Differences between subgroups were examined using chi-squared tests and logistic regression analysis. Estimates are stated with 95% CI. RESULTS: The majority of the participants (87.6 (86.6-88.6)% to 92.6 (91.7-93.3)%) correctly identified the test concept and the main condition being screened for. Fewer participants (16.4 (15.3-17.6)% to 43.3 (41.8-44.8)%) correctly recognized test accuracy and the potential risk of adverse findings other than Down syndrome. Knowledge level was positively associated with length of education (adjusted ORs 1.0 (0.8-1.4) to 3.9 (2.4-6.4)) and participation in the screening program (adjusted OR 0.9 (0.6-1.3) to 5.9 (3.9-8.8)). Participation in an individual information session was weakly associated with more knowledge. CONCLUSION: The majority of the pregnant women correctly identified the test concept and the main condition being screened for. The pregnant women were found less knowledgeable on test accuracy and drawbacks.

A systematic study of solution and processing parameters on nanofiber morphology using a new electrospinning apparatus.

We assembled a new electrospinning apparatus and used poly(ethylene oxide) as a model polymer to perform a systematic study on the influence of solution and processing parameters on the morphology of electrospun nanofibers. Solution parameters studied were polymer concentration and molecular mass. The solvent used, 60 wt% water, 40 wt% ethanol, was the same throughout the study. Processing parameters analyzed were: solution feed rate, needle tip-collector distance and electrostatic potential difference between the needle and collector. Solution viscosity increased both with polymer concentration and molecular mass. Polymer concentration plays a decisive role on the outcome of the electrospinning process: a low concentration led to the formation of beaded fibers; an intermediate concentration yielded good quality fibers; a high concentration resulted in a bimodal size distribution and at even higher concentration a distributed deposition. Fiber diameter increased with polymer molecular mass and higher molecular masses are associated with a higher frequency of splaying events. Fiber diameter increased linearly with solution feed rate. While an increase in needle-collector distance represents a weaker electric field, a greater distance to be covered by the fibers and a longer flight time, presumably favoring the formation of thinner fibers, as solvent evaporation leads to a local increase of concentration and viscosity, viscoelastic forces opposing stretching caused an increase of fiber diameter with needle-collector distance. A higher voltage applied at the needle is associated with a higher charging of the polymer and a higher electrical current through it ultimately leading to incomplete solvent evaporation and merged fibers being produced. Controlling the charging of the polymer independently of the electric field strength was achieved by applying a voltage to the collector while distance and potential difference were kept constant. The increased electrostatic repulsion associated with an increase of the high voltage applied to the needle led to the disappearance of merged fibers.

Aberrant signaling in T-cell acute lymphoblastic leukemia: biological and therapeutic implications.

T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous disease with respect to phenotype, gene expression profile and activation of particular intracellular signaling pathways. Despite very significant improvements, current therapeutic regimens still fail to cure a portion of the patients and frequently implicate the use of aggressive protocols with long-term side effects. In this review, we focused on how deregulation of critical signaling pathways, in particular Notch, PI3K/Akt, MAPK, Jak/STAT and TGF-beta, may contribute to T-ALL. Identifying the alterations that affect intracellular pathways that regulate cell cycle and apoptosis is essential to understanding the biology of this malignancy, to define more effective markers for the correct stratification of patients into appropriate therapeutic regimens and to identify novel targets for the development of specific, less detrimental therapies for T-ALL.

Aberrant signaling in T-cell acute lymphoblastic leukemia: biological and therapeutic implications

T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous disease with respect to phenotype, gene expression profile and activation of particular intracellular signaling pathways. Despite very significant improvements, current therapeutic regimens still fail to cure a portion of the patients and frequently implicate the use of aggressive protocols with long-term side effects. In this review, we focused on how deregulation of critical signaling pathways, in particular Notch, PI3K/Akt, MAPK, Jak/STAT and TGF-ß, may contribute to T-ALL. Identifying the alterations that affect intracellular pathways that regulate cell cycle and apoptosis is essential to understanding the biology of this malignancy, to define more effective markers for the correct stratification of patients into appropriate therapeutic regimens and to identify novel targets for the development of specific, less detrimental therapies for T-ALL.