Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response.

Obsessive-compulsive disorder (OCD) affects 2-3% of the population. One-third of patients are poorly responsive to conventional therapies, and for a subgroup, gamma knife capsulotomy (GKC) is an option. We examined lesion characteristics in patients previously treated with GKC through well-established programs in Providence, RI (Butler Hospital/Rhode Island Hospital/Alpert Medical School of Brown University) and São Paulo, Brazil (University of São Paolo). Lesions were traced on T1 images from 26 patients who had received GKC targeting the ventral half of the anterior limb of the internal capsule (ALIC), and the masks were transformed into MNI space. Voxel-wise lesion-symptom mapping was performed to assess the influence of lesion location on Y-BOCS ratings. General linear models were built to compare the relationship between lesion size/location along different axes of the ALIC and above or below-average change in Y-BOCS ratings. Sixty-nine percent of this sample were full responders (≥35% improvement in OCD). Lesion occurrence anywhere within the targeted region was associated with clinical improvement, but modeling results demonstrated that lesions occurring posteriorly (closer to the anterior commissure) and dorsally (closer to the mid-ALIC) were associated with the greatest Y-BOCS reduction. No association was found between Y-BOCS reduction and overall lesion volume. GKC remains an effective treatment for refractory OCD. Our data suggest that continuing to target the bottom half of the ALIC in the coronal plane is likely to provide the dorsal-ventral height required to achieve optimal outcomes, as it will cover the white matter pathways relevant to change. Further analysis of individual variability will be essential for improving targeting and clinical outcomes, and potentially further reducing the lesion size necessary for beneficial outcomes.

The Effects of Subjective Cognitive Decline on APOE Genotype Disclosure in the Butler Hospital Alzheimer's Prevention Registry.

BACKGROUND: Subjective cognitive decline (SCD) and APOE genotyping are both instrumental in identifying high-risk individuals for Alzheimer's disease (AD) prevention trials. OBJECTIVE: This study examined the relationship between SCD and the impact of APOE disclosure on the psychological and behavioral health of cognitively unimpaired individuals. Design/Setting/Participant: We recruited 189 trial volunteers (mean age 66, 65% female, 96% White), from the Butler Hospital Alzheimer's Prevention Registry. Participants completed screening for cognitive impairment and a psychological readiness assessment before learning their APOE genotype, and were followed for 6 months after. RESULTS: SCD had a modest, temporary impact on mood and event-related distress following APOE disclosure, specifically on those who were ε4 carriers. The presence of SCD (SCD+) did not compound the AD genetic test-specific distress related to learning that one was an ε4 carrier. SCD also did not moderate changes in perceived AD risk, with all non-carriers showing a more rapid decrease in perceived risk over time than carriers. Counterintuitively, those without SCD (SCD-) reported taking more steps in future-directives than the SCD+ group at baseline and after disclosure, potentially suggesting that those with SCD may have subtle executive declines that limit future-oriented actions or fear-avoidance behaviors. Further, the SCD- group was more accurate in recalling their APOE status and the recall accuracy correlated with their broad knowledge about APOE as a risk gene for AD. CONCLUSION: Our findings support the safety and tolerability of APOE disclosure in research volunteers regardless of their SCD statuses, but further studies are warranted to include diverse individuals and those pursuing testing through direct-to-consumer services outside of traditional research settings.

Diagnostic and therapeutic approach of central sleep apnea in heart failure - the role of adaptive servo-ventilation. A statement of the Portuguese society of pulmonology and the Portuguese sleep association.

It is known that patients with heart failure (HF) have an increased risk of developing central sleep apnoea (CSA), with Cheyne-Stokes respiration. The development of servo-ventilation aimed to treat CSA and improve the quality of life (QoL) of these patients. A large randomized clinical study, SERVE-HF, was conducted in order to test this theory in patients with HF and reduced ejection fraction (HFrEF). The results from this trial seemed to indicate that, in these patients, there was no beneficial effect of the assisted ventilation in CSA treatment. More surprisingly, an increased rate of all-cause or cardiovascular mortality was observed. This has led to dramatic changes in clinical practice, with decreased frequency of servo-ventilation prescription across Europe, including Portugal, due to changes in the guidelines. However, SERVE-HF was conducted only in severe systolic HF patients with CSA, and caution must be taken when extrapolating these results to HF patients with preserved ejection fraction or CSA patients without HF. The study also showed poor adherence, methodological and statistical gaps, including study design, patient selection, data collection and analysis, treatment adherence, and group crossovers, which have not been discussed in the trial as potential confounding factors and raise several concerns. Moreover, the adaptive servo-ventilation (ASV) device used in SERVE-HF was unable to lower the minimum support pressure below 3 mm H20, and this has been suggested as one of the probable contributing reasons to the excess mortality observed in this study. This limitation has since been solved, and this ASV device is no longer used. This paper describes the results of a Portuguese Task Force on the treatment of central sleep apnoea in patients with chronic HF.

Hospital context in surgical site infection following colorectal surgery: a multi-level logistic regression analysis.

BACKGROUND: Surgical site infections (SSIs) are associated with poor health outcomes. Their incidence is highest after colorectal surgery, with little improvement in recent years. The role of hospital characteristics is undetermined. AIM: To investigate whether SSI incidence after colorectal surgery varies between hospitals, and whether such variance may be explained by hospital characteristics. METHODS: Data were retrieved from the electronic platform of the Directorate General of Health, from 2015 to 2019. Hospital characteristics were retrieved from publicly available data on the Portuguese public administration. Analysis considered a two-level hierarchical data structure, with individuals clustered in hospitals. To avoid overfitting, no models were built with more than one hospital characteristic. Cluster-level associations are presented through median odds ratio (MOR) and intraclass cluster coefficient (ICC). Beta coefficients were used to assess the contextual effects. FINDINGS: A total of 11,219 procedures from 18 hospitals were included. The incidence of SSI was 16.8%. The ICC for the null model was 0.09. Procedural variables explained 25% of the variance, and hospital dimension explained another 17%. More than 50% of SSI variance remains unaccounted for. After adjustment, heterogeneity between hospitals (MOR: 1.51; ICC: 0.05) was still found. No hospital characteristic was significantly associated with SSI. CONCLUSION: Procedural variables and hospital dimension explain almost half of SSI variance and should be taken into account when implementing prevention strategies. Future research should focus on compliance with preventive bundles and other process indicators in hospitals with significantly less SSI in colorectal surgery.

Protective role of Portuguese natural mineral waters on skin aging: in vitro evaluation of anti-senescence and anti-oxidant properties.

Natural mineral waters (NMWs) emerge from the earth as springs and their beneficial therapeutic effect has been empirically recognized in different countries. Portugal has diverse NMW resources that are sought for the relief of different afflictions including dermatological complications. However, there is a lack of scientific validation supporting this empiric knowledge. In this study, we aimed to screen the in vitro bioactivity of Portuguese NMWs with different chemical profiles, namely sulfurous/bicarbonate/sodic (SBS), bicarbonate/magnesium, sulfated/calcic, sulfurous/chlorinated/sodic, sulfurous/bicarbonate/fluoridated/sodic, and chlorinated/sodic, focusing on aging-related skin alterations. Mouse skin fibroblasts and macrophages were exposed to culture medium prepared in different NMWs. Cellular viability was evaluated by MTT assay and etoposide-induced senescence was analyzed through the beta-galactosidase staining kit. Wound healing was investigated by the scratch assay, and phototoxicity/photoprotection after UVA irradiation was evaluated using a neutral red solution. ROS production was quantified using the 2'7'-dichlorofluorescin diacetate dye, and the activity of superoxide dismutase (SOD) was analyzed by a commercial kit after lipopolysaccharide exposure. NMWs within the SBS profile demonstrated anti-senescence activity in skin fibroblasts, along with a variable effect on cellular viability. Among the tested NMWs, two decreased cellular senescence and preserved cell viability and were therefore selected for subsequent studies, together with a SBS NMW with therapeutic indications for dermatologic diseases. Overall, the selected NMW promoted wound healing in skin fibroblasts and activated SOD in macrophages, thus suggesting an anti-oxidant effect. None of the NMWs prevented phototoxicity after UV irradiation. Our results shed a light on the anti-aging potential of Portuguese NMW, supporting their putative application in cosmetic or medical products.

Electrochemical and sonochemical advanced oxidation processes applied to tartrazine removal. Influence of operational conditions and aqueous matrix.

Tartrazine degradation was investigated by electrochemical and sonochemical oxidation processes. Anodic oxidation was carried out using boron-doped diamond (BDD) electrodes. The influence of current density and dye initial concentration on the removal of tartrazine from water was analyzed. The experimental results indicate that total removal of tartrazine was obtained, and Chemical Oxygen Demand (COD) and Total Organic Carbon (TOC) removals of up to 94.4% and 72.8% were achieved, respectively. To optimize the process, the pollutant removal percentage, the kinetic rate constant, and the TOC removal efficiency were chosen as target variables. Moreover, sonochemical oxidation experiments at a high-frequency range of cavitation (up to 1 MHz) were performed to establish the influence of three different operating variables, namely ultrasound frequency (0.5-1.1 MHz), ultrasound power (2.0-26.6 W ⋅L-1), and pulse-stop ratio (5:1-1:1). The process was also analyzed in terms of kinetics and energy costs. The kinetics resulted to be three times faster for the electrochemical process. However, the calculated energy costs were very similar, at least at long treatment times. Finally, the influence of three aqueous matrices was investigated. According to the experimental results, the natural occurrence of chloride and/or nitrate ions in water strongly conditions the rate of the process, although at least 90% of tartrazine removal was achieved within the first 50 min of treatment.

Anti-inflammatory potential of Portuguese thermal waters.

In light of Medical Hydrology, thermal waters (TW) are all-natural mineral waters that emerge inside a thermal resort and have therapeutic applications. Their beneficial effect has been empirically recognized for centuries, being indicated for symptom alleviation and/or treatment of several diseases, almost all associated with inflammation. Indeed, an anti-inflammatory effect has been attributed to many different Portuguese TW but there is no scientific validation supporting this empiric knowledge. In the present study, we aimed to investigate the anti-inflammatory properties of 14 TW pertaining to thermal centers located in the Central Region of Portugal, and grouped according to their ionic profile. Mouse macrophage cells stimulated with lipopolysaccharide (LPS), a Toll-like receptor 4 agonist, were exposed to culture medium prepared in TW. Metabolism, nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression levels and the scavenging capacity of TW, were investigated in vitro. 11 out of 14 TW reduced NO production and/or iNOS expression, and/or scavenging activity, in macrophages exposed to LPS. The sulphated/calcic TW did not show any effect on at least one of the inflammatory parameters evaluated. Two sulphurous/bicarbonate/sodic TW and the sulphurous/chlorinated/sodic TW promoted an increase in NO production and/or iNOS expression. Our results validate, for the first time, the anti-inflammatory properties of Portuguese TW, supporting their therapeutic use in the treatment of inflammation-related diseases and promoting their putative application in cosmetic products and medical devices.

Oncofertility case report: live birth 10 years after oocyte in vitro maturation and zygote cryopreservation.

PURPOSE: This study aims to report a case of urgent fertility preservation in an oncological patient with collection of immature oocytes in the absence of ovarian stimulation that, through in vitro maturation (IVM), followed by ICSI and cryopreservation of zygotes resulted, 10 years later, in the live birth of a healthy baby. METHODS: In September 2008, our clinic performed IVM in a 32-year-old woman diagnosed with a ductal invasive carcinoma with positive estradiol receptors, negative progesterone receptors and positive human epidermal growth factor receptor 2. The retrieval of immature oocytes was performed in the absence of ovarian stimulation after a simple mastectomy and prior to any chemotherapy treatment. The compact cumulus-oocyte complexes (COCs) collected were placed in Lag medium for 2 h, followed by incubation in IVM medium, supplemented with heat inactivated patient serum, recombinant FSH, and recombinant LH. After 30 h in culture, cumulus cells were removed, the metaphase II oocytes were microinjected, and the zygotes obtained were cryopreserved. In 2017, the zygotes were thawed and cultured until day 3. One embryo was transferred and the other cryopreserved. RESULTS: Four compact COCs were collected and subjected to IVM. Two oocytes reached metaphase II and were microinjected. Two zygotes were obtained and were cryopreserved at the two pronuclear stage. Approximately 9 years later, the two zygotes were thawed and cultured until day 3. An embryo with 10 cells was transferred and implanted, resulting in the birth of a healthy baby. CONCLUSIONS: In cases where urgency to start adjuvant therapy requires immediate oocyte collection, IVM may be the only option to obtain fully competent mature oocytes allowing for effective preservation of the reproductive potential.

Efectividad de los regímenes tratar y extender vs. pro re nata para el tratamiento de degeneración macular neovascular vinculada a la edad: una comparación en un entorno real / Effectiveness of treat-and-extend versus pro re nata regimens in the treatment of Neovascular Age Macular Degeneration: A Real World Comparison

OBJETIVO: Evaluar y comparar los resultados visuales y morfológicos de regímenes de tratamiento pro re nata (PRN) y tratar-y-extender (T&E) a tres años en la práctica clínica real. MÉTODOS: Un estudio retrospectivo de pacientes con degeneración macular vinculada a la edad neovascular (DMEN) tratadas con anti-VEGF con tres años de seguimiento continuo y sin tratamientos anti-VEGF anteriores. Se midieron la mejor agudeza visual corregida (MAVC), el espesor foveal central (EFC) y el número de inyecciones intravítreas para determinar diferencias estadísticas entre ambos grupos al inicio y a lo largo del seguimiento. RESULTADOS: Se incluyeron en el estudio un total de 240 ojos, 170 en el grupo PRN y 70 en el grupo T&E. A los 12 meses la ganancia media con respecto al inicio de MAVC (en letras ETDRS) llegó a su punto más alto en el grupo T&E (+ 6,38 ± 13,32; p = 0,25). En el grupo PRN, MAVC llegó al máximo a los tres meses y disminuyó lentamente hasta el final del seguimiento. Con ambos regímenes, desde el inicio el EFC continuó disminuyendo hasta el segundo año (PRN -138,81 [-846,7 a +162,77] y T&E -81 [-604 a +100] μm, p = 0,06). Posteriormente, el grupo T&E mantuvo esta tendencia, llegando al nivel más bajo de EFC a los 36 meses, mientras que el grupo PRN mostró un aumento en los valores de EFC (PRN -104 [-807,7 a +297] μm y T&E -103 [-575 a +244], μm p = 0,63). Los pacientes tratados con el régimen T&E recibieron un número significativamente mayor de inyecciones (PRN 16,3 ± 7,6 vs. T&E 23,9 ± 9,4, p <0,01). CONCLUSIÓN: Los resultados demostraron una tendencia de T&E a conseguir valores más altos de MAVC, llegando al máximo a los 12 meses, y grosores menores de EFC al final de tres años. A pesar del mayor número de inyecciones en el grupo T&E, la media de MAVC revirtió a los valores de base a los tres años

PURPOSE: Evaluate and compare the visual and morphological results of Pro re nata (PRN) and treat-and-extend (T&E) treatment regimens at 3 years in real world clinical practice. METHODS: Retrospective study of patients with neovascular age macular: degeneration (AMD) treated with anti-VEGF with 3 years of continuous follow-up and no previous anti-VEGF treatment. Best corrected visual acuity (BCVA), central foveal thickness (CFT) and number of intravitreal injections outcomes were tested for statistical differences between the two groups at baseline and during follow-up. RESULTS: A total of 240 eyes were included in the study, 170 in the PRN group and 70 in the T&E group. At 12 months, mean BCVA (ETDRS letters) gain from baseline was at its highest point in the T&E group (+6.38 ± 13.32; p = 0.25). In the PRN group, BCVA peaked at 3 months and slowly decreased until end of follow-up. With both regimens, from baseline, CFT continued to decrease until the second year (PRN -138.81 [-846.7 to +162.77] and T&E -81 [-604 to +100] μm, p = 0.06). After that, T&E group maintained this tendency, reaching the lowest CFT value at 36 months, whereas PRN group showed an increased in CFT values (PRN -104 [-807.7 to +297] μm and T&E -103 [-575 to +244], μm p = 0.63). Patients treated with T&E regimen received a significantly higher number of injections (PRN 16.3 ± 7.6 vs T&E 23.9 ± 9.4, p < 0.01). CONCLUSION: Our results demonstrated a trend towards for T&E to achieve higher marks in BCVA, peaking at 12 months, and lower CFT thickness at the end of three years. Despite the higher number of injections performed in the T&E group the mean BCVA reverts to baseline values at 3 years

Effectiveness of treat-and-extend versus pro re nata regimens in the treatment of Neovascular Age Macular Degeneration: A Real World Comparison. / Efectividad de los regímenes tratar y extender vs. pro re nata para el tratamiento de degeneración macular neovascular vinculada a la edad: una comparación en un entorno real.

PURPOSE: Evaluate and compare the visual and morphological results of Pro re nata (PRN) and treat-and-extend (T&E) treatment regimens at 3 years in real world clinical practice. METHODS: Retrospective study of patients with neovascular age macular degeneration (AMD) treated with anti-VEGF with 3 years of continuous follow-up and no previous anti-VEGF treatment. Best corrected visual acuity (BCVA), central foveal thickness (CFT) and number of intravitreal injections outcomes were tested for statistical differences between the two groups at baseline and during follow-up. RESULTS: A total of 240 eyes were included in the study, 170 in the PRN group and 70 in the T&E group. At 12 months, mean BCVA (ETDRS letters) gain from baseline was at its highest point in the T&E group (+6.38±13.32; p=0.25). In the PRN group, BCVA peaked at 3 months and slowly decreased until end of follow-up. With both regimens, from baseline, CFT continued to decrease until the second year (PRN -138.81 [-846.7 to +162.77] and T&E -81 [-604 to +100] µm, p=0.06). After that, T&E group maintained this tendency, reaching the lowest CFT value at 36 months, whereas PRN group showed an increased in CFT values (PRN -104 [-807.7 to +297] µm and T&E -103 [-575 to +244], µm p=0.63). Patients treated with T&E regimen received a significantly higher number of injections (PRN 16.3±7.6 vs T&E 23.9 ±9.4, p<0.01). CONCLUSION: Our results demonstrated a trend towards for T&E to achieve higher marks in BCVA, peaking at 12 months, and lower CFT thickness at the end of three years. Despite the higher number of injections performed in the T&E group the mean BCVA reverts to baseline values at 3 years.

Selecting and improving activated homogeneous catalytic processes for pollutant removal. Kinetics, mineralization and optimization.

The degradation of a model pollutant, tartrazine, very used in food industry and usually present in WWTPs effluents and surface waters, was investigated by nine activated homogeneous catalytic processes, namely, Fe3+/H2O2, Fe2+/H2O2, UV/H2O2, UV/S2O82-, UV/Fe2+/H2O2, UV/Fe3+/H2O2, UV, VIS/Fe3+/H2O2, and VIS/Fe3+/H2O2/C2O42-. In order to compare the mineralization and oxidation ability of each process, the removal of dye, chemical oxygen demand (COD) and total organic carbon (TOC) were analyzed, as well as the overall kinetic rate constant. Also, the different oxidation path-ways (direct photolysis and/or oxidation by free radicals) were estimated for each system. After the comparison, the Fenton process, which had the highest mineralization values, was tested in luminous and dark phases using designed experiments, and the influences of all operating variables were studied by RSM.

Posterior talar process as a suitable cell source for treatment of cartilage and osteochondral defects of the talus.

Osteochondral defects of the ankle are common lesions affecting the talar cartilage and subchondral bone. Current treatments include cell-based therapies but are frequently associated with donor-site morbidity. Our objective is to characterize the posterior process of the talus (SP) and the os trigonum (OT) tissues and investigate their potential as a new source of viable cells for application in tissue engineering and regenerative medicine. SP and OT tissues obtained from six patients were characterized by micro-computed tomography and histological, histomorphometric and immunohistochemical analyses. Proliferation and viability of isolated cells were evaluated by MTS assay, DNA quantification and live/dead staining. The TUNEL assay was performed to evaluate cell death by apoptosis. Moreover, the production of extracellular matrix was evaluated by toluidine blue staining, whereas cells phenotype was investigated by flow cytometry. Characterization of ankle explants showed the presence of a cartilage tissue layer in both SP and OT tissues, which represented at least 20%, on average, of the explant. The presence of type II collagen was detected in the extracellular matrix. Isolated cells presented a round morphology typical of chondrocytes. In in vitro studies, cells were viable and proliferating for up to 21 days of culture. No signs of apoptosis were detected. Flow-cytometry analysis revealed that isolated cells maintained the expression of several chondrocytic markers during culture. The results indicated that the SP and OT tissues were a reliable source of viable chondrocytes, which could find promising applications in ACI/MACI strategies with minimal concerns regarding donor zone complications. Copyright © 2015 John Wiley & Sons, Ltd.

Middle-Aged Diabetic Females and Males Present Distinct Susceptibility to Alzheimer Disease-like Pathology.

Type 2 diabetes (T2D) is a highly concerning public health problem of the twenty-first century. Currently, it is estimated that T2D affects 422 million people worldwide with a rapidly increasing prevalence. During the past two decades, T2D has been widely shown to have a major impact in the brain. This, together with the cognitive decline and increased risk for dementia upon T2D, may arise from the complex interaction between normal brain aging and central insulin signaling dysfunction. Among the several features shared between T2D and some neurodegenerative disorders (e.g., Alzheimer disease (AD)), the impairment of insulin signaling may be a key link. However, these may also involve changes in sex hormones' function and metabolism, ultimately contributing to the different susceptibilities between females and males to some pathologies. For example, female sex has been pointed as a risk factor for AD, particularly after menopause. However, less is known on the underlying molecular mechanisms or even if these changes start during middle-age (perimenopause). From the above, we hypothesized that sex differentially affects hormone-mediated intracellular signaling pathways in T2D brain, ultimately modulating the risk for neurodegenerative conditions. We aimed to evaluate sex-associated alterations in estrogen/insulin-like growth factor-1 (IGF-1)/insulin-related signaling, oxidative stress markers, and AD-like hallmarks in middle-aged control and T2D rat brain cortices. We used brain cortices homogenates obtained from middle-aged (8-month-old) control Wistar and non-obese, spontaneously T2D Goto-Kakizaki (GK) male and female rats. Peripheral characterization of the animal models was done by standard biochemical analyses of blood, plasma, or serum. Steroid sex hormones, oxidative stress markers, and AD-like hallmarks were given by specific ELISA kits and colorimetric techniques, whereas the levels of intracellular signaling proteins were determined by Western blotting. Albeit the high levels of plasma estradiol and progesterone observed in middle-aged control females suggested that they were still under their reproductive phase, some gonadal dysfunction might be already occurring in T2D ones, hence, anticipating their menopause. Moreover, the higher blood and lower brain cholesterol levels in female rats suggested that its dysfunctional uptake into the brain cortex may also hamper peripheral estrogen uptake and/or its local brain steroidogenic metabolism. Despite the massive drop in IGF-1 levels in females' brains, particularly upon T2D, they might have developed some compensatory mechanisms towards the maintenance of estrogen, IGF-1, and insulin receptors function and of the subsequent Akt- and ERK1/2-mediated signaling. These may ultimately delay the deleterious AD-like brain changes (including oxidative damage to lipids and DNA, amyloidogenic processing of amyloid precursor protein and increased tau protein phosphorylation) associated with T2D and/or age (reproductive senescence) in female rats. By demonstrating that differential sex steroid hormone profiles/action may play a pivotal role in brain over T2D progression, the present study reinforces the need to establish sex-specific preventive and/or therapeutic approaches and an appropriate time window for the efficient treatment against T2D and AD.

Endogenous Factors in the Recovery of Reproductive Function After Testicular Injury and Cancer.

The testes are one of the most delicate organs in the male body and highly susceptible to the exogenous influences capable of inducing cell damage. Cancer therapies are well known to negatively affect the male reproductive tract with a severe impairment of spermatogenesis and infertility. The present work aimed to systematically review the available information about the different endogenous factors (hormonal and nonhormonal) that may have protective or advantageous properties on the recovery of male reproductive function after gonadal injury. Furthermore, the perspective that these endogenous molecules could act as cryoprotectants to improve the quality of cryopreserved semen samples was also discussed. The knowledge reviewed herein allowed to identify promising factors able to mitigate the male fertility problems arising either from oncological treatments or other gonadal damage, and opened new possibilities to ameliorate the recovery of spermatogenesis or to preserve fertility.

The Emerging Role of Regucalcin as a Tumor Suppressor: Facts and Views.

Regucalcin (RGN) is a multifunctional protein that was first described as a calcium (Ca2+)-binding protein playing a relevant role in the maintenance of intracellular Ca2+ concentration. However, due to its downregulated expression with aging, RGN is also known as senescence marker protein-30. The RGN protein is an X-chromosome gene product, whose transcription is regulated by a myriad of hormonal and non-hormonal factors. Besides the well-known role in Ca2+ homeostasis, RGN has also been linked to the control of several intracellular signaling pathways, and basic biological processes, such as oxidative stress, cell proliferation, apoptosis, and metabolism. RGN has been shown to have antioxidant properties by its activity reducing the production of reactive oxygen species and increasing the antioxidant defenses. The role of RGN suppressing cell proliferation is associated with the regulation of expression of oncogenes and tumor suppressor genes. It results clear that all the existent knowledge implicates RGN in the control of the main biological processes actually recognized as the hallmarks of cancer. Moreover, it has been shown that tumor onset and progression are underpinned by the loss of RGN expression, whereas RGN overexpression showed to have a protective role against the development of chemicallyinduced tumors. This review describes the mechanisms that control the tissue expression of RGN and discusses the experimental evidence that indicate RGN as a new tumor suppressor protein.

Respiratory functional evaluation and pulmonary hyperinflation in asymptomatic smokers: Preliminary study.

OBJECTIVES: To investigate the respiratory function and lung hyperinflation in asymptomatic smokers without previous pulmonary pathology and with normal chest radiography. To identify tobacco-related diseases and to correlate tobacco consumption, duration of exposure to tobacco smoke and urinary cotinine with the existence of tobacco-related disease. MATERIAL AND METHODS: Case-controlled study with pairing by sex, age, and body mass index. CASE DEFINITION: smokers who presented to the first appointment of smoking cessation at the Hospital Sousa Martins (HSM) without respiratory symptoms and with normal chest radiography. Definition of control: users without current and/or past tobacco exposition and with plethysmography and chest radiography at HSM within normal parameters. RESULTS: Reductions in FEV1/FVC, FEF 75%, FEF 25-75% and the cardiothoracic index were detected in smokers and showed a moderated inverse correlation of TLC (with statistical meaning) compared with the control group. Approximately 31.2% of the smokers showed extrapulmonary disease related to tobacco, and 9.38% of the smokers exhibited subclinical chronic obstructive pulmonary disease (COPD). Smokers with tobacco-related diseases presented a mean age and RV/TLC ratio superior to smokers without pathology. DISCUSSION: The reduction of the mean values of FEV1/FVC, FEF 75%, FEF 25-75% and the cardiothoracic index seems to indicate precocious pulmonary dysfunction. This work aims to reveal the importance of detecting premonitory anomalies of pulmonary disease during the subclinical phase in patients at risk. Smoking must be considered a factor of multisystemic repercussion; thus, intervention opportunities in this particular group must not be wasted. This preliminary study identifies potentially promising variables with the aim of testing the hypothesis that there can be premonitory alterations in COPD, according to its evolution versus reversibility after smoking cessation. This work will be concluded in a future study.