Chest computed tomography findings of patients infected with Covid-19 and their association with disease evolution stages.

INTRODUCTION: To describe CT findings in patients with confirmed Covid-19 infection and correlate them with the disease evolution stages. METHODS: This is a historical cohort observational analytical study carried out with outpatients, inpatients, and emergency patients from a private hospital in Maceió/AL, Brazil. The final sample consisted of 390 patients with positive RT-PCR for Covid-19 with available laboratory tests and chest CT results. RESULTS: The most frequent initial symptoms were cough, fever, dyspnea and headache. The most commonly found comorbidities were hypertension, diabetes mellitus and obesity. A total of 22% of the CT scans showed no alterations; ground-glass opacity was the most frequently found one. There was a significant association between age, comorbidities, pulmonary involvement, ground-glass opacity, mosaic attenuation and percentage of pulmonary involvement with death. The analysis of the disease stages showed a significant association with laboratory data (CRP and platelet levels), ground-glass opacity and mosaic attenuation with the disease evolution stages in relation to the days since symptom onset. CONCLUSION: The disease evolution of Covid-19 occurs in stages, and this study describes tomographic findings in patients with confirmed Covid-19 infection and shows they vary depending on the disease evolution stages. IMPLICATIONS FOR PRACTICE: This paper provides important addition to the various records that have been accumulated through the Covid-19 pandemic.

Entropy production as a tool for characterizing nonequilibrium phase transitions.

Nonequilibrium phase transitions can be typified in a similar way to equilibrium systems, for instance, by the use of the order parameter. However, this characterization hides the irreversible character of the dynamics as well as its influence on the phase transition properties. Entropy production has been revealed to be an important concept for filling this gap since it vanishes identically for equilibrium systems and is positive for the nonequilibrium case. Based on distinct and general arguments, the characterization of phase transitions in terms of the entropy production is presented. Analysis for discontinuous and continuous phase transitions has been undertaken by taking regular and complex topologies within the framework of mean-field theory (MFT) and beyond the MFT. A general description of entropy production portraits for Z_{2} ("up-down") symmetry systems under the MFT is presented. Our main result is that a given phase transition, whether continuous or discontinuous has a specific entropy production hallmark. Our predictions are exemplified by an icon system, perhaps the simplest nonequilibrium model presenting an order-disorder phase transition and spontaneous symmetry breaking: the majority vote model. Our work paves the way to a systematic description and classification of nonequilibrium phase transitions through a key indicator of system irreversibility.

Severe asthma in obese patients: Improvement of lung function after treatment with omalizumab.

INTRODUCTION: Asthma and obesity have a considerable impact on public health and their prevalence is increasing. Obesity is a known risk factor for asthma and can make it more difficult to control. Omalizumab is recommended in patients with severe allergic persistent asthma. The aim of this study was to assess the impact of omalizumab treatment in obese asthmatic patients with poorly controlled severe persistent asthma. METHODOLOGY: A non-interventional, prospective study was conducted, in an outpatient asthma clinic. All patients with severe asthma who started treatment with omalizumab were included and followed over 12 months. The study population was divided into two groups (obese and non-obese) for statistical analysis (descriptive and comparative analysis). RESULTS: Thirty-two patients (19 obese) were followed. After 12 months of omalizumab treatment, there was a statistically significant improvement in body mass index, number of exacerbations in the previous year, rescue medication, disease control and lung function, in the whole population. At the end of the study obese patients had a significantly better lung function (FEV1) than non-obese. DISCUSSION: As described in the literature, there was a significant reduction in the number of exacerbations in the previous year, rescue medication and better disease control, in the whole population. In relation to lung function, about which published data are inconsistent, treatment with omalizumab significantly improved it in obese patients. CONCLUSION: Our study showed that omalizumab significantly improved asthma control, reduced rescue medication and asthma exacerbations in all the population; and for the first time showed that obese patients achieved significantly improved lung function.

Reference equations for the 6-minute walk distance in healthy Portuguese subjects 18-70 years old.

INTRODUCTION: Six-minute walk test (6MWT) is used for evaluating functional exercise capacity. To the best of our knowledge, there are no reference equations to predict six-minute walk distance (6MWD) for the Portuguese population. The aims of the present study were to measure anthropometric data and 6MWD in a sample of healthy Portuguese population, to establish reference equations to predict 6MWD and to compare our equations with those obtained by previously published studies. METHODS: We conducted an observational prospective study. We consecutively recruited 158 healthy 18-70 years old subjects from Porto district, who performed two 6MWTs using a standardized protocol. The best 6MWD was used for further analysis. RESULTS: The mean 6MWD was 627.8m (SD=73.3m). The variables that were significantly associated with the 6MWD were age, sex, BMI and ΔHR (Heart Rateat the end of the test-HRat rest). We found three explanatory models for 6MWD, the best with an explanatory power of 38%: 6MWD=721.7-1.6×Age-4.0×BMI+0.9×ΔHR+58.4×Sex. We verified that 6MWD decreased 1.6m per year of age, and 4.0m per unit of BMI and increased 0.892m per beat per minute. Moreover, on average, males walk 58.4m more than females (p<0.001). Applying equations from other studies to our population resulted in an overestimation or underestimation of the 6MWD. CONCLUSION: The present study was the first to describe the 6MWD in healthy Portuguese people aged 18-70 years old and to propose predictive equations. These can contribute to improving the evaluation of Caucasian Mediterranean patients with diseases that affect their functional capacity.

Portuguese consensus document for the management of alpha-1-antitrypsin deficiency.

Alpha-1-antitrypsin deficiency (AATD) is a genetic autosomal codominant disorder caused by mutations in SERPINA1 gene. It is one of the most prevalent genetic disorders, although it remains underdiagnosed. Whereas at international level there are several areas of consensus on this disorder, in Portugal, inter-hospital heterogeneity in clinical practice and resources available have been adding difficulties in reaching a diagnosis and in making therapeutic decisions in this group of patients. This raised a need to draft a document expressing a national consensus for AATD. To this end, a group of experts in this field was created within the Portuguese Pulmonology Society - Study group on AATD, in order to elaborate the current manuscript. The authors reviewed the existing literature and provide here general guidance and extensive recommendations for the diagnosis and management of AATD that can be adopted by Portuguese clinicians from different areas of Medicine. This article is part of a supplement entitled "Portuguese consensus document for the management of alpha-1-antitrypsin deficiency" which is sponsored by Sociedade Portuguesa de Pneumologia.

Interplay between sympathetic nervous system and inflammation in aseptic loosening of hip joint replacement.

Inflammation is a common symptom in joint disorders such as rheumatoid arthritis, osteoarthritis (OA) and implant aseptic loosening (AL). The sympathetic nervous system is well known to play a critical role in regulating inflammatory conditions, and imbalanced sympathetic activity has been observed in rheumatoid arthritis. In AL it is not clear whether the sympathetic nervous system is altered. In this study we evaluated the systemic and local profile of neuroimmune molecules involved in the interplay between the sympathetic nervous system and the periprosthetic inflammation in hip AL. Our results showed that periprosthetic inflammation does not trigger a systemic response of the sympathetic nervous system, but is mirrored rather by the impairment of the sympathetic activity locally in the hip joint. Moreover, macrophages were identified as key players in the local regulation of inflammation by the sympathetic nervous system in a process that is implant debris-dependent and entails the reduction of both adrenergic and Neuropetide Y (NPY)-ergic activity. Additionally, our results showed a downregulation of semaphorin 3A (SEMA3A) that may be part of the mechanism sustaining the periprosthetic inflammation. Overall, the local sympathetic nervous system emerges as a putative target to mitigate the inflammatory response to debris release and extending the lifespan of orthopedic implants.

Does any association exist between Chronic Obstructive Pulmonary Disease and Erectile Dysfunction? The DECODED study.

INTRODUCTION: Erectile dysfunction (ED) is the inability to achieve or maintain an erection for satisfactory sexual activity. Recent studies have shown an association between ED and chronic obstructive pulmonary disease (COPD). However, this issue is often ignored. We aimed to evaluate the ED prevalence in COPD patients and its risk factors and to study the impact of dyspnea in sexual activity. METHODS: Cross-sectional study that included sexually active male patients with COPD. The International Index of Erectile Function (IIEF-5) questionnaire evaluated ED and the Respiratory Experiences with Sexuality Profile (RESP) was used to evaluate the impact of dyspnea on sexual activity. Risk factors for mild-moderate or moderate ED were determined using logistic regression. RESULTS: 84 patients were consecutively assessed for eligibility, 67 were included (median age: 65 years, 13% never-smokers). Twenty two percent had COPD 2011-GOLD A; 22% GOLD B, 14% GOLD C and 42% GOLD D. Fifty-eight patients (87%) had some degree of ED: 26 (45%) mild, 20 (34%) mild-moderate and 12 (21%) moderate ED. ED occurred in all GOLD stages of COPD, mainly in GOLD B and D stages. Higher CAT score was independently associated to mild-moderate/moderate ED. Most patients (85%) reported dyspnea during their sexual activity but 72% had never talked about it with their physician. CONCLUSIONS: ED is highly prevalent among COPD patients and it is more severe in patients with higher CAT scores. Dyspnea affects their sexual activity but this is not a topic often discussed between patients and doctors, something which needs to be improved.

Effects of positive airway pressure therapy on cardiovascular and metabolic markers in males with obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular/metabolic complications. Some analytical parameters (homocysteine, glycemic and lipidic profiles) are recognized markers of these consequences. Limited data is available on the association of these markers and OSAS's severity/response to positive airway pressure therapy (PAP). MATERIAL AND METHODS: In this prospective study we analyzed polysomnographic and analytical data of male patients admitted to sleep laboratory. The aim was to evaluate metabolic/cardiovascular markers in snorers and OSAS patients, to relate with sleep parameters and PAP response. One-hundred and three patients were included, and 73 (71%) were OSAS patients. OSAS patients were similar to snorers except for higher body mass index (BMI) and dyslipidemia. Severe OSAS patients showed higher glycemia, HbA1c, insulin, and insulin resistance, and lower HDL cholesterol in comparison to mild-moderate (p<0.05, p<0.05, p<0.001, p<0.001, p<0.05, respectively). Glycemic profile and triglycerides were slightly correlated with OSAS severity. 46 OSAS patients were submitted to 6 months of PAP, with a statistical decrease in mean values of homocysteine, glycemia, total and LDL cholesterol (p<0.05, p<0.05, p<0.05, respectively), and in glycemia and LDL cholesterol in severe group only (p<0.05, p<0.05, respectively). RESULTS: This study demonstrated an association between glucose metabolism parameters and triglycerides with OSAS severity underlying the complexity of the process leading to cardiovascular/metabolic complications in this disorder. Moreover, homocysteine, glycemic and lipidic profiles changed significantly after 6 months of PAP therapy in OSAS, supporting its cardiovascular and metabolic protective effect. CONCLUSION: Our study has reinforced the importance of analytical cardiovascular/metabolic evaluation as complementary tool of diagnosis/treatment response in OSAS.

Saturated salt solution: a further step to a formaldehyde-free embalming method for veterinary gross anatomy.

In the field of veterinary anatomy, most of the specimens used in practical sessions are perfused with fixatives. Thus, they can be used for a longer time, reducing the number of animals for educational purposes. Formalin is the most commonly used fixative, consisting of a 37% formaldehyde solution. However, formaldehyde is a powerful irritant of the eyes and airways and is considered carcinogenic, causing nasopharyngeal cancer in exposed workers and professionals. In the present study, we explored an alternative method to avoid the use of formaldehyde in specimens used for gross anatomy practical sessions. We propose an inexpensive, non-toxic fixative that is available worldwide, such as sea salt. This method consists of a continuous perfusion of saturated salt solution for a period of 6-8 h, enabling drainage of the solution to avoid a weight increase of the specimen, and allowing salt to be retained in the tissue. The method is based on recirculation of the saturated salt solution instead of maceration. Perfused specimens retained their natural consistency and joint mobility, with no blood, resembling a piece of meat from the slaughterhouse. They could be used immediately without a maceration period, or stored in the fridge until use and then kept in a bath of saturated salt solution for future conservation. In the case of the former, no refrigeration was needed. The specimens did not have an irritating or offensive smell, and could be used for long sessions (several hours per day) and stored for long periods. However, the blood vessels used for perfusion determine the results: a less invasive approach (through common carotid arteries) gave good preservation of the musculoskeletal system, whereas more invasive access to cannulate the abdominal aorta and vena cava caudalis was required to achieve better preservation of the viscera. In conclusion, we propose that perfusion followed by immersion in a saturated salt solution is a good alternative method for the preservation of specimens used in the practical teaching of gross veterinary anatomy. It is a very simple and inexpensive technique, and is much healthier for users than traditional formalin. Moreover, specimens can be preserved for prolonged periods, and maintain a similar appearance and consistency to fresh material.

Diabetic foot ulcer development risk classifications' validation: A multicentre prospective cohort study.

AIMS: To prospectively validate the existing classifications to stratify subjects with diabetes mellitus (DM) by their risk of diabetic foot ulcer (DFU), in high and low risk settings. METHODS: A prospective multicentre cohort study was conducted, including 446 subjects with DM without active DFU followed in the hospital or primary care setting. Demographic, clinical characterization variables, and those included in the classifications were collected at baseline. Subjects were followed for 1year, until DFU or death. RESULTS: In our sample, with a mean age of 65years, 52% were male; 32 developed a DFU, 7 required an amputation and 18 died. Differences were found between participants' characteristics and classifications' accuracy according to the setting. The great majority of the variables were associated with higher DFU risk. Globally, classifications were highly and equally valid, positive predictive values (PV) were inferior to 40%, negative PV superior to 90% and area under the receiver operating characteristic curve superior to 0.75. DISCUSSION: All the existing classifications are valid to be applied in high risk clinical context and have a very high capacity to categorize as low risk those subjects that will not develop a DFU. Further research is needed in the primary care setting.

Decellularized human colorectal cancer matrices polarize macrophages towards an anti-inflammatory phenotype promoting cancer cell invasion via CCL18.

Macrophages are frequently identified in solid tumors, playing important roles in cancer progression. Their remarkable plasticity makes them very sensitive to environmental factors, including the extracellular matrix (ECM). In the present work, we investigated the impact of human colorectal tumor matrices on macrophage polarization and on macrophage-mediated cancer cell invasion. Accordingly, we developed an innovative 3D-organotypic model, based on the decellularization of normal and tumor tissues derived from colorectal cancer patients' surgical resections. Extensive characterization of these scaffolds revealed that DNA and other cell constituents were efficiently removed, while native tissue characteristics, namely major ECM components, architecture and mechanical properties, were preserved. Notably, normal and tumor decellularized matrices distinctly promoted macrophage polarization, with macrophages in tumor matrices differentiating towards an anti-inflammatory M2-like phenotype (higher IL-10, TGF-ß and CCL18 and lower CCR7 and TNF expression). Matrigel invasion assays revealed that tumor ECM-educated macrophages efficiently stimulated cancer cell invasion through a mechanism involving CCL18. Notably, the high expression of this chemokine at the invasive front of human colorectal tumors correlated with advanced tumor staging. Our approach evidences that normal and tumor decellularized matrices constitute excellent scaffolds when trying to recreate complex microenvironments to understand basic mechanisms of disease or therapeutic resistance.

Mycobacterium avium infection in Portugal.

BACKGROUND: Although the incidence rates of non-tuberculous mycobacteria (NTM) have been increasing in many countries, the basic epidemiology of NTM remains to be fully understood. OBJECTIVE: To assess the incidence, clinical relevance and geographical distribution of NTM disease in Portugal and to identify demographic and clinical characteristics associated with Mycobacterium avium complex (MAC) disease. METHODS: Information stored in an electronic database of all NTM cases reported over an 11-year period was retrospectively reviewed. Significant demographic and clinical characteristics of MAC disease (vs. having any other NTM disease) were determined using multiple logistic regression models. RESULTS: We identified 632 patients, mostly male, native Portuguese, with pulmonary disease, predominantly from Lisbon and Porto. The annual incidence of NTM disease was 0.54 per 100 000 population. The annual number of NTM cases increased throughout the study period. MAC was most frequently isolated. MAC disease was positively (and significantly) associated with being female, age >45 years and human immunodeficiency virus infection. CONCLUSIONS: The increasing incidence of NTM over the study period emphasises the importance of NTM as a public health issue. This study provides important information for health care professionals and a basis for further study of NTM in Portugal.

Three-dimensional scaffolds of fetal decellularized hearts exhibit enhanced potential to support cardiac cells in comparison to the adult.

A main challenge in cardiac tissue engineering is the limited data on microenvironmental cues that sustain survival, proliferation and functional proficiency of cardiac cells. The aim of our study was to evaluate the potential of fetal (E18) and adult myocardial extracellular matrix (ECM) to support cardiac cells. Acellular three-dimensional (3D) bioscaffolds were obtained by parallel decellularization of fetal- and adult-heart explants thereby ensuring reliable comparison. Acellular scaffolds retained main constituents of the cardiac ECM including distinctive biochemical and structural meshwork features of the native equivalents. In vitro, fetal and adult ECM-matrices supported 3D culture of heart-derived Sca-1(+) progenitors and of neonatal cardiomyocytes, which migrated toward the center of the scaffold and displayed elongated morphology and excellent viability. At the culture end-point, more Sca-1(+) cells and cardiomyocytes were found adhered and inside fetal bioscaffolds, compared to the adult. Higher repopulation yields of Sca-1(+) cells on fetal ECM relied on ß1-integrin independent mitogenic signals. Sca-1(+) cells on fetal bioscaffolds showed a gene expression profile that anticipates the synthesis of a permissive microenvironment for cardiomyogenesis. Our findings demonstrate the superior potential of the 3D fetal microenvironment to support and instruct cardiac cells. This knowledge should be integrated in the design of next-generation biomimetic materials for heart repair.

Alpha-1 antitrypsin deficiency caused by a novel mutation (p.Leu263Pro): Pi*ZQ0gaia - Q0gaia allele.

Severe alpha-1 antitrypsin deficiency (AATD) is generally associated with PI*ZZ genotype and less often with combinations of PI*Z, PI*S, and other rarer deficiency or null (Q0) alleles. Severe AATD predisposes patients to various diseases, including pulmonary emphysema. Presented here is a case report of a young man with COPD and AATD. The investigation of the AATD showed a novel mutation p.Leu263Pro (c.860T>C), which was named Q0gaia (Pi*ZQ0gaia). Q0gaia is associated with very low or no detectable serum concentrations of AAT.

Macrophages stimulate gastric and colorectal cancer invasion through EGFR Y(1086), c-Src, Erk1/2 and Akt phosphorylation and smallGTPase activity.

The interactions between cancer cells and their microenvironment are crucial for malignant progression, as they modulate invasion-related activities. Tumor-associated macrophages are generally considered allies in the process of tumor progression in several types of cancer, although their role on gastric and colorectal carcinomas is still poorly understood. In this report, we studied the influence of primary human macrophages on gastric and colorectal cancer cells, considering invasion, motility/migration, proteolysis and activated intracellular signaling pathways. We demonstrated that macrophages stimulate cancer cell invasion, motility and migration, and that these effects depend on matrix metalloproteinase (MMP) activity and on the activation of epidermal growth factor receptor (EGFR) (at the residue Y(1086)), PLC-γ (phospholipase C-gamma) and Gab1 (GRB2-associated binding protein-1), as evidenced by siRNA (small interference RNA) experiments. Epidermal growth factor (EGF)-immunodepletion impaired macrophage-mediated cancer cell invasion and motility, suggesting that EGF is the pro-invasive and pro-motile factor produced by macrophages. Macrophages also induced gastric and colorectal cancer cell phosphorylation of Akt, c-Src and ERK1/2, and led to an increase of RhoA and Cdc42 activity. Interestingly, whereas macrophage-mediated cancer cell c-Src and ERK1/2 phosphorylation occurred downstream EGFR activation, Akt phosphorylation seems to be a parallel event, taking place in an EGFR-independent manner. The involvement of EGF, EGFR-downstream signaling partners and MMPs in macrophage-mediated invasion provides novel insights into the molecular crosstalk established between cancer cells and macrophages, opening new perspectives for the design of new and more efficient therapeutic strategies to counteract cancer cell invasion.

Correlations between the biochemistry and mechanical states of a sea-urchin ligament: a mutable collagenous structure.

Mutable collagenous tissues (MCTs) of echinoderms can be regarded as intelligent and dynamic biomaterials, due to their ability to reversibly change their mechanical properties in a short physiological time span. This mutability phenomenon is nervously mediated and involves secreted factors of the specialized 'juxtaligamental' cells, which, when released into the extracellular matrix (ECM), change the cohesive forces between collagen fibrils. MCTs exist in nature in several forms, including some associated with echinoderm autotomy mechanisms. Since the molecular mechanism of mutability is still incompletely understood, the aim of this work was to provide a detailed biochemical analysis of a typical mutable collagenous structure and to identify possible correlations between its biochemistry and mechanical states. A better understanding of the mutability phenomena is likely to provide a unique opportunity to develop new concepts that can be applied in the design of dynamic biomaterial for tissue regeneration, leading to new strategies in regenerative medicine. The MCT model used was the compass depressor ligament (CDL) of a sea urchin (Paracentrotus lividus), which was analyzed in different mechanical states, mimicking the mutability phenomenon. Spectroscopic techniques, namely Fourier transform infrared (FT-IR) and confocal Raman microscopy, were used to identify the specific molecular components that contribute to the CDL biochemical microenvironment and to investigate the possibility that remodelling/synthesis of new ECM components occurs during the mutability phenomenon by analogy with events during pregnancy in the uterine cervix of mammals (which also consists mainly of mechanically adaptable connective tissues). The results demonstrate that CDL ECM includes collagen with biochemical similarities to mammalian type I collagen, as well as sulphated glycosaminoglycans (GAGs). CDL mutability seems to involve a molecular rearrangement of the ECM, without synthesis of new ECM components. Although there were no significant biochemical differences between CDLs in the various mechanical states were observed. However, subtle adjustments in tissue hydration seemed to occur, particularly during stiffening.

Aging and fluctuation-dissipation ratio in a nonequilibrium q-state lattice model.

A generalized version of the nonequilibrium linear Glauber model with q states in d dimensions is introduced and analyzed. The model is fully symmetric, its dynamics being invariant under all permutations of the q states. Exact expressions for the two-time autocorrelation and response functions on a d-dimensional lattice are obtained. In the stationary regime, the fluctuation-dissipation theorem holds, while in the transient the aging is observed with the fluctuation-dissipation ratio leading to the value predicted for the linear Glauber model.

Iodine intake in Portuguese pregnant women: results of a countrywide study.

BACKGROUND: Iodine is the key element for thyroid hormone synthesis, and its deficiency, even moderate, is harmful in pregnancy, when needs are increased, because of its potential deleterious effects on fetal brain development. In Portugal, no recent data on iodine intake exists. The objective of this countrywide study was to analyze iodine status in pregnant Portuguese women in order to propose adequate measures to the health authorities. SUBJECTS AND METHODS: Using a fast colorimetric method, urine iodine concentration (UIC) was evaluated in 3631 pregnant women followed in 17 maternity hospitals from hinterland and coastal areas in Continental Portugal and the Portuguese islands of Açores and Madeira. RESULTS: Median UIC value was 84.9 µg/l (range 67.6-124.1) in Continental Portugal, 69.5 µg/l in Madeira, and 50.0 µg/l in Açores. The percentage of satisfactory values (>150 µg/l) was 16.8, ranging from 8.8 to 34.1 in the Continent, and being 8.2 in Madeira and 2.3 in Açores. The percentage of values below 50 µg/l was 23.7, ranging from 14.0 to 37.4 in the Continent, 33.7 in Madeira, and 50.0 in Açores. CONCLUSIONS: Our results point to an inadequate iodine intake in pregnant women assisted in most Portuguese maternity hospitals. Considering the potential deleterious effects of inadequate iodine supply in pregnancy, iodine supplementation is strongly recommended in this period of life.