Accuracy of multidetector computed tomography with maximum intensity projection technique in the assessment of fissure integrity.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) is a potential treatment for patients with severe emphysema, performed through the placement of unidirectional endobronchial valves (EBVs). Their benefits are only achieved in patients that significantly reduce lobar volume, and it is mandatory that the fissures are complete. Fissure evaluation is preferably done by computed tomography, but little is known if its evaluation corresponds to the anatomical findings. The aim of this study is to evaluate the accuracy of thoracic radiologists in the identification of complete fissures by multidetector computed tomography (MDCT) using maximum intensity projection (MIP) technique, compared with direct anatomical evaluation. METHODS: Prospective study, conducted in a single institution. Patients submitted to thoracic surgery had their fissures classified as complete or incomplete by thoracic surgeons and their preoperative chest scans evaluated by three radiologists, blinded for surgical evaluation. With the intraoperative categorization as a reference, the accuracy and concordance of the three thoracic radiologists' evaluation were calculated. The most experienced radiologist evaluated the fissures at two different moments to estimate the intra-observer agreement. RESULTS: There were included 67 patients, being 37 (55%) males, with a mean age of 64 years. The accuracy of radiological identification of complete fissures ranged from 76.8% for left posterior oblique fissure to 85.1% for left anterior oblique fissure, with the best performance achieved by the most experienced radiologist. The concordance of the radiological evaluation for fissure integrity compared to the surgical assessment (k) was 0.53-0.68. Intra-observer agreement ranged from 0.74 to 0.87. CONCLUSIONS: The evaluation of the fissure integrity by MDCT analysis using MIP technique by thoracic radiologists had high accuracy among the thoracic radiologists.

Influence of noise level and seniority in the workplace on the SAL, ELI and percentage of hearing loss indices in the diagnosis and prevention of hearing loss in the working population.

INTRODUCTION: This research relates the most important work-related factors affecting the development of hearing loss to the main methods used as medical assessment criteria in the diagnosis of occupational deafness. These criteria are the Speech Average Loss Index (SAL), the Early Loss Index (ELI) and the Percentage of Hearing Loss, and are applied to data obtained from audiograms performed on workers in occupational medical examinations. METHOD: Depending on the assessment method selected, these often return different results in grading an individual's hearing status and predicting how it will evolve. To address this problem, medical examinations (including audiograms) were carried out on a heterogeneous sample of 1,418 workers in Spain, from which demographic or personal data (gender, age, etc.), occupational data (noise level to which each individual is exposed, etc.) and other non-work-related factors (exposure to noise outside work, family history, etc.) were also gathered. Using Bayesian Networks, the conditional probability of an individual developing hearing loss was obtained taking into account all these factors and, specifically, noise level and length of service in the workplace. Sensitivity analyses were also carried out using the three scales (SAL, ELI and Percentage Hearing Loss Index), proving their suitability as tools the diagnosis and prediction of deafness. These networks were validated under the Receiver Operating Characteristic curve (ROC) criterion and in particular by the Area Under the Curve (AUC). RESULTS: The results show that all three methods are deficient in so far as detecting preventive hearing problems related to noise in most workplaces. CONCLUSIONS: The most restrictive methods for detecting possible cases of deafness are the SAL index and the Percentage Loss Index. The ELI index is the least restrictive of the three methods, but it is not able to discriminate the causes of hearing problems in an individual caused by exposure to noise, either by its intensity level or by the time of exposure to noise. Practical Applications: The use of the three methods in the field of occupational risk prevention is extremely limited and it seems reasonable to think that there is a need for the construction of new scales to correct or improve the existing ones.

Concurrent Akt, ERK1/2 and AMPK Activation by Obestatin Inhibits Apoptotic Signaling Cascades on Nutrient-Deprived PC12 Cells.

Targeting apoptosis in the ischemic penumbra is a rational therapeutic approach for restricting cerebral infarct volume after clinical stroke. The present work explored the capability of the obestatin peptide, as a novel approach to inhibit apoptotic signaling cascades on PC12 cells. According to the results, obestatin treatment significantly reduced nutrient deprivation-induced apoptotic cell death. The protective effects were related to the regulation of the anti-apoptotic protein, BCL-2, and the apoptotic protein caspase-3. This encompasses the control of apoptosis by the interplay between Akt, ERK1/2 and AMPK signaling pathways. The activation of Akt and AMPK was concomitant with the phosphorylation of their downstream targets, GSK3 and ACC, respectively. Besides, obestatin also causes FoxO1 nuclear export supporting the prevention of the apoptosome formation. The concurrent activation of Akt and AMPK by obestatin via the GPR39 receptor, supports a role for this system in the balance concerning the catabolic and the anabolic signaling to sustain cellular function and viability. Furthermore, these results provide both an insight into how the obestatin/GPR39 system regulates anti-apoptotic pathways, and a framework for ascertaining how this system can be optimally targeted in treatment of brain cell death after stroke.

Influence of the products of biomass combustion processes on air quality and cancer risk assessment in rural environmental (Spain).

Polycyclic aromatic hydrocarbons (PAHs) associated with atmospheric particles represent a significant risk to human health. This issue is even more relevant in environments where biomass combustion processes are considered as the major potential emission sources, such as the rural ecosystem. This study aimed to assess the levels of PM10-bound PAHs in several rural locations, their distribution along a year and how weather variables could influence them. Also, we focused on the emission sources and the comparison of the PAH mixtures to assess similitude among the sampling points. PM10-bound PAHs levels were monitored at three rural locations (north, center, and south) of Spain between April 2017 and February 2018. The study revealed that there were substantial differences regarding the levels of ΣPAHs, being higher in the central zone (IS; 65.4 mg/m3), then in the south (VA; 35.8 ng/m3) and finally in the north (NA; 20.9 ng/m3). IS and VA showed a similar distribution of emission sources, and temperature and wind speed seemed to influence negatively over the levels of PAHs likely. At both locations, PAH levels ran parallel throughout the year, with maximum levels during cold seasons and a greater presence of high molecular weight PAHs; however, the levels of PAHs and the most representative PAHs differed. On the other hand, NA was characterized for having another distribution of emission sources, which determined other representative PAHs, higher levels during spring, and a similar presence of high/medium/low molecular weight. Finally, the levels of ambient air PAHs represented an acceptable risk to people.

An optimized approach for estimating benzene in ambient air within an air quality monitoring network.

Benzene is a carcinogenic air pollutant for which European legislation has set an annual limit and criteria for the number of fixed monitoring sites within air quality networks (AQMN). However, due to the limited number of fixed sites for benzene measurement, exposure data are lacking. Considering the relationship between benzene levels and other variables monitored within an AQMN, such as NO2, O3, temperature, solar radiation, and accumulated precipitation, this study proposes an approach for estimating benzene air concentrations from the related variables. Using the data of the aforementioned variables from 23 fixed stations during 2016-2017, the proposed approach was able to forecast benzene concentration for 2018 with high confidence, providing enriched data on benzene exposure and its trends. Moreover, the spatial distribution of the estimated versus the most representative benzene levels was quite similar. Finally, an artificial neural network identified the most representative fixed benzene monitoring sites within the AQMN.

Translation and validation of the Filipino version of the University of Washington Quality of Life Questionnaire (UW-QOL) for patients with head and neck cancer

Objective@#To translate the University of Washington Quality of Life (UW-QOL) questionnaire into Filipino and to validate it among a sample of patients with head and neck cancer. @*Methods@#Design: Cross-sectional study. Setting: Tertiary Government Training Hospital. Participants: 33 patients.@*Results@#A total of 33 patients were recruited in this study. Eighteen (54.5%) were male, and 15 (45.5%) were female aged 24-79 years old (mean age 52.85 ± 11.81 years old) completed the study. All items in the Filipino translation of the UW-QOL had a content validity index. The raters in face validation had 100% agreement in almost all items except for the appropriateness of font size and space of the questionnaire. The Cronbach’s alpha of the Filipino version of the questionnaire was 0.8596. The alpha score when each of the items was deleted remained within the range of 0.83 – 0.86. The intraclass correlation coefficients of all items were greater than 0.9. For all items, there were no significant difference observed between the test and retest scores. @*Conclusion@#This study showed that the Filipino translation of the UW-QOL is culturally adapted, internally consistent and stable. It is as reliable as the original English version in assessing health related QOL, and valid for assessing HR-QOL among patients with head and neck cancers.

Role of systematic pelvic and para-aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy cycles for high-grade serous ovarian carcinoma.

INTRODUCTION: We analyzed the role of systematic pelvic and para-aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy (NACT) cycles for advanced high-grade serous ovarian carcinoma. MATERIALS AND METHODS: We retrospectively reviewed patients with advanced ovarian carcinoma who underwent NACT with carboplatin-paclitaxel between 2008 and 2016. Patients were included only if they had FIGO IIIC-IVB high-grade serous carcinoma with clinically negative lymph nodes after six NACT cycles (carboplatin-paclitaxel) and underwent complete or near complete cytoreduction. Patients with partial lymphadenectomy or bulky nodes were excluded. Patients who underwent systematic pelvic and aortic lymphadenectomy and those who did not undergo lymph node dissection were compared. Progression-free and overall survivals were analyzed using the Kaplan-Meier method. RESULTS: Totally, 132 patients with FIGO IIIC-IVB epithelial ovarian carcinoma were surgically treated after NACT. Sixty patients were included (39 and 21 in the lymphadenectomy and nonlymphadenectomy group, respectively); 40% had suspicious lymph nodes before NACT. Patient characteristics, blood transfusion numbers, and complication incidence were similar between the groups. In the lymphadenectomy group, 12 patients (30.8%) had histologically positive lymph nodes and the surgical time was longer (229 vs. 164 min). The median overall survival in the lymphadenectomy and nonlymphadenectomy groups, respectively, was 56.7 (95% CI 43.4-70.1) and 61.2 (21.4-101.0) months (p = 0.934); the corresponding disease-free survival was 8.1 (6.2-10.1) and 8.3 (5.1-11.6) months (p = 0.878). Six patients exclusively presented with lymph node recurrence. CONCLUSIONS: Systematic lymphadenectomy after six NACT cycles may have no influence on survival.

Obestatin signalling counteracts glucocorticoid-induced skeletal muscle atrophy via NEDD4/KLF15 axis.

BACKGROUND: A therapeutic approach for the treatment of glucocorticoid-induced skeletal muscle atrophy should be based on the knowledge of the molecular mechanisms determining the unbalance between anabolic and catabolic processes and how to re-establish this balance. Here, we investigated whether the obestatin/GPR39 system, an autocrine signalling system acting on myogenesis and with anabolic effects on the skeletal muscle, could protect against chronic glucocorticoid-induced muscle atrophy. METHODS: In this study, we used an in vivo model of muscle atrophy induced by the synthetic glucocorticoid dexamethasone to examine the liaison molecules that define the interaction between the glucocorticoid receptor and the obestatin/GPR39 systems. The findings were extended to in vitro effects on human atrophy using human KM155C25 myotubes. RESULTS: KLF15 and FoxO transcription factors were identified as direct targets of obestatin signalling in the control of proteostasis in skeletal muscle. The KLF15-triggered gene expression program, including atrogenes and FoxOs, was regulated via KLF15 ubiquitination by the E3 ubiquitin ligase NEDD4. Additionally, a specific pattern of FoxO post-translational modification, including FoxO4 phosphorylation by Akt pathway, was critical in the regulation of the ubiquitin-proteasome system. The functional cooperativity between Akt and NEDD4 in the regulation of FoxO and KLF15 provides integrated cues to counteract muscle proteostasis and re-establish protein synthesis. CONCLUSIONS: The effective control of FoxO activity in response to glucocorticoid is critical to counteract muscle-related pathologies. These results highlight the potential of the obestatin/GPR39 system to fine-tune the effects of glucocorticoids on skeletal muscle wasting.

Local and Systemic STAT3 and p65 NF-KappaB Expression as Progression Markers and Functional Targets for Patients With Cervical Cancer.

Cervical cancer, which main etiologic factor is Human Papillomavirus (HPV) infection, continues to be a burden for public health systems in developing countries. Our laboratory has been working with the hypothesis that signals generated in the tumor microenvironment can modulate local and systemic immune responses. In this context, it would be reasonable to think that tumors create pro-tumoral bias in immune cells, even before they are recruited to the tumor microenvironment. To understand if and how signaling started in the tumor microenvironment can influence cells within the tumor and systemically, we investigated the expression of key proteins in signaling pathways important for cell proliferation, viability, immune responses and tolerance. Besides, we used detection of specific phosphorylated residues, which are indicative of activation for Akt, CREB, p65 NFκB, and STAT3. Our findings included the observation of a significant STAT3 expression increase and p65 NFκB decrease in circulating leukocytes in correlation with lesion grade. In light of those observations, we started investigating the result of the inhibition of STAT3 in a tumor experimental model. STAT3 inhibition impaired tumor growth, increased anti-tumor T cell responses and decreased the accumulation of myeloid cells in the spleen. The concomitant inhibition of NFκB partially reversed these effects. This study indicates that STAT3 and NFκB are involved in immunomodulatory tumor effects and STAT3 inhibition could be considered as therapy for patients with cervical cancer.

Indoor and Outdoor PM10-Bound PAHs in an Urban Environment. Similarity of Mixtures and Source Attribution.

Given that the European Union lays down air quality objectives associated with outdoor environments, indoor air mixtures' study acquires a remarkable relevance. This work aims to submit a stepwise methodological framework for assessing similarities between indoor and outdoor air mixtures and apportioning potential emission sources. For reaching this goal, PM10 particles were systematically and simultaneously collected at an indoor (dominant emission sources free) and outdoor environment during a year to determine the PAH content in both air mixtures. Broadly, outdoor PAHs levels were higher than at the indoor location, supporting a strong association between both mixtures (r = 0.968, p > 0.001), mainly during the cold period (r = 0.896, p > 0.001). The light molecular weight PAHs were highlighted at the indoor site, in particular to naphthalene and anthracene. Outdoor emission sources influenced the indoor PAH levels, especially high and medium molecular weight PAHs. The local-traffic load was identified as a dominant pollution source responsible for more than half PAHs determined at both environments. Therefore, the control of outdoor emission sources would be translated into an improvement of indoor air quality.

Assessment and Modeling of the Influence of Age, Gender, and Family History of Hearing Problems on the Probability of Suffering Hearing Loss in the Working Population.

Hearing loss affects hundreds of millions of people all over the world, leading to several types of disabilities, ranging from purely physical to psychological and/or social aspects. A proper analysis to ascertain the main risk factors is essential in order to diagnose early and treat adequately. An exploratory analysis based on a heterogeneous sample of 1418 workers is presented in order to identify the main trigger factors for hearing loss. On the one hand, we recorded several medical and environmental parameters, and on the other, we created a model based on Bayesian networks in order to be able to infer the probability of hearing loss considering different scenarios. This paper focuses on three parameters: gender, age, and a family history of hearing problems. The results obtained allow us to infer or predict the best or worst auditory level for an individual under several different scenarios. The least relevant factor is the existence of a family history of deafness, followed by the gender factor, which slopes considerably toward better hearing for females, and most prominent of all, the age factor, given the large differences identified between the various age groups when the gender and family history of deafness variables remain constant.

Planning stand-alone electricity generation systems, a multiple objective optimization and fuzzy decision making approach.

This paper presents a fuzzy-multiple objective optimization methodology to plan stand-alone electricity generation systems. The optimization process considers three main objectives, namely technology cost, environmental and societal impacts. For each feasible solution of the Pareto set, a system reliability index is evaluated along the lifetime of the project. As a key contribution, the decision making process is carried out by applying a fuzzy satisfaction method (FSM). The FSM accounts simultaneously four key performance indexes (KPI): technical, economic, environmental and social. The novelty of the proposal lies on the inclusion of societal impact (local wealth creation) in the FSM used here to select the more appropriate solution. Previous contributions on FSM only accounts two of four indexes considered in this paper. The methodology was applied in a Colombian case study. The results show the importance of the simultaneous consideration of technical, economic, environmental and social objectives in the evaluation of off-grid energization solutions.

Particle-associated polycyclic aromatic hydrocarbons in a representative urban location (indoor-outdoor) from South Europe: Assessment of potential sources and cancer risk to humans.

PM10 -bound polycyclic aromatic hydrocarbons (PAHs) levels were monitored at urban locations (outdoor/indoor) within the city of Madrid between May 2017 and April 2018. Fourteen PAH congeners were measured, potential emission sources were identified as were potential carcinogenic risks. The ΣPAHs averaged 0.577 and 0.186 ng/m3 in outdoor and indoor air, with a high linear correlation per individual mean PAH and month. The largest contributors to the ΣPAHs were the high-molecular-weight PAHs. Principal component analysis-multiple linear regression results showed that emissions from diesel and vehicular processes explained 27% and 23% of the total variance of outdoor and indoor air, while combustion processes accounted for 30% and 25% in ambient and indoor air, respectively. During the cold season, biomass burning plus coal and wood combustion were additional sources of outdoor emissions. The heavy-, medium- and light-molecular-weight PAH originating from outdoor sources accounted for 72%, 80%, and ~60% of the indoor levels of the three respective PAH groups. Average BaP concentration was 0.029 and 0.016 ng/m3 in outdoor and indoor air, respectively. Estimated BaPeq concentration averaged 0.072, 0.035, and 0.027 ng/m3 for outdoor, indoor, and indoor-generated individual PAH concentrations, respectively. The estimated carcinogenic risk falls within the range of acceptable risk targeted by the US-EPA.

Publisher Correction: Obestatin controls skeletal muscle fiber-type determination.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Data on the main working conditions with influence on the development of hearing loss amongst the occupational population in Spain.

Obtaining reliable and objective data on certain working conditions is necessary to analyse the causes and variables that can influence the development of hearing loss amongst the working population. Objective occupational data have been collected from a heterogeneous sample of 1418 workers in Spain, see "How activity type, time on the job and noise level on the job affect the hearing of the working population. Using Bayesian networks to predict the development of hipoacusia" (Barrero et al., 2018) [1]. Among the main factors analysed are the noise levels to which these workers are exposed, measured at their respective workstations, and the assessment of their hearing status, evaluated by audiometric medical tests. These factors provide information to predict the development of hypoacusia.

Improvement of Duchenne muscular dystrophy phenotype following obestatin treatment.

BACKGROUND: This study was performed to test the therapeutic potential of obestatin, an autocrine anabolic factor regulating skeletal muscle repair, to ameliorate the Duchenne muscular dystrophy (DMD) phenotype. METHODS AND RESULTS: Using a multidisciplinary approach, we characterized the ageing-related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4-, 8-, and 18-week-old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8-week-old mdx mice (n = 5/group). The findings were extended to in vitro effects on human immortalized DMD myotubes. An analysis of TAs revealed an age-related loss of preproghrelin expression, as precursor of obestatin, in mdx mice. Administration of obestatin resulted in a significant increase in tetanic specific force (33.0% ± 1.5%, P < 0.05), compared with control mdx mice. Obestatin-treated TAs were characterized by reduction of fibres with centrally located nuclei (10.0% ± 1.2%, P < 0.05) together with an increase in the number of type I fibres (25.2% ± 1.7%, P < 0.05) associated to histone deacetylases/myocyte enhancer factor-2 and peroxisome proliferator-activated receptor-gamma coactivator 1α axis, and down-regulation of ubiquitin E3-ligases by inactivation of FoxO1/4, indexes of muscle atrophy. Obestatin reduced the level of contractile damage and tissue fibrosis. These observations correlated with decline in serum creatine kinase (58.8 ± 15.2, P < 0.05). Obestatin led to stabilization of the sarcolemma by up-regulation of utrophin, α-syntrophin, ß-dystroglycan, and α7ß1-integrin proteins. These pathways were also operative in human DMD myotubes. CONCLUSIONS: These results highlight the potential of obestatin as a peptide therapeutic for preserving muscle integrity in DMD, thus allowing a better efficiency of gene or cell therapy in a combined therapeutic approach.

Humanização da Assistência ao Parto e Puerpério: Novos Desafios

O vídeo fala sobre humanização da assistência ao parto e puerpério, humanização das práticas de assistência obstétrica ( baseada em evidencias científicas), fala também do acesso ao serviço de pré-natal e vinculação a uma maternidade de referencia para o parto e aborda o parto e nascimento.

Hypermetabolism is a deleterious prognostic factor in patients with amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: The aim of this study was to investigate patients with amyotrophic lateral sclerosis in order to determine their nutritional, neurological and respiratory parameters, and survival according to metabolic level. METHODS: Nutritional assessment included resting energy expenditure (REE) measured by indirect calorimetry [hypermetabolism if REE variation (ΔREE) > 10%] and fat mass (FM) using impedancemetry. Neurological assessment included the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score. Survival analysis used the Kaplan-Meier method and multivariate Cox model. RESULTS: A total of 315 patients were analysed. Median age at diagnosis was 65.9 years and 55.2% of patients were hypermetabolic. With regard to the metabolic level (ΔREE: < 10%, 10-20% and >20%), patients with ΔREE > 20% initially had a lower FM(29.7% vs. 32.1% in those with ΔREE ≤10%; P = 0.0054). During follow-up, the median slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised tended to worsen more in patients with ΔREE > 20% (-1.4 vs. -1.0 points/month in those with ΔREE ≤10%; P = 0.07). Overall median survival since diagnosis was 18.4 months. ΔREE > 20% tended to increase the risk of dying compared with ΔREE ≤10% (hazard ratio, 1.33; P = 0.055). In multivariate analysis, an increased REE:FM ratio was independently associated with death (hazard ratio, 1.005; P = 0.001). CONCLUSIONS: Hypermetabolism is present in more than half of patients with amyotrophic lateral sclerosis. It modifies the body composition at diagnosis, and patients with hypermetabolism >20% have a worse prognosis than those without hypermetabolism.