Cell therapy with adipose tissue-derived human stem cells in the urinary bladder improves detrusor contractility and reduces voiding residue.

Detrusor hypocontractility (DH) is a disease without a gold standard treatment in traditional medicine. Therefore, there is a need to develop innovative therapies. The present report presents the case of a patient with DH who was transplanted with 2 x 106 adipose tissue-derived mesenchymal stem cells twice and achieved significant improvements in their quality of life. The results showed that cell therapy reduced the voiding residue from 1,800 mL to 800 mL, the maximum cystometric capacity from 800 to 550 mL, and bladder compliance from 77 to 36.6 mL/cmH2O. Cell therapy also increased the maximum flow from 3 to 11 mL/s, the detrusor pressure from 08 to 35 cmH2O, the urine volume from 267 to 524 mL and the bladder contractility index (BCI) value from 23 to 90. The International Continence on Incontinence Questionnaire - Short Form score decreased from 17 to 8. Given the above, it is inferred that the transplantation of adipose tissue-derived mesenchymal stem cells is an innovative and efficient therapeutic strategy for DH treatment and improves the quality of life of patients affected by this disease.

Pediatric maxillary expansion has a positive impact on hearing? A systematic review and meta-analysis.

OBJECTIVE: Hearing loss is a highly prevalent condition in the pediatric population. Pediatric maxillary expansion is a widespread treatment to address transverse maxillary deficiency. First reports describing an association between improvements for patients with HL and PME initiated in the 1960s. In this systematic review and meta-analysis we aim to review the role of maxillary expansion in reducing conductive hearing loss in pediatric population. REVIEW METHODS: Pubmed (Medline), the Cochrane Library, EMBASE and Trip Database were checked. Main outcome was expressed as the difference between air-bone gap, compliance, ear volume and conductive hearing thresholds before and after treatment and the 95% confidence interval. RESULTS: A total of 10 studies (218 patients) met inclusion criteria. The pooled data in the meta-analysis under a random effects model shows a statistically significant difference of 10.57dB mean reduction after palatal expansion. The air-bone gap was significantly reduced by 5.39dB (CI 95% 3.68, 7.10). Compliance and volume were assessed in three studies, with a non-significant positive difference in the compliance (0.14) and a statistically significant difference for volume (0.80) after palatal expansion. CONCLUSION: This systematic review and meta-analysis found a positive effect of pediatric maxillary expansion in conductive hearing loss in well-select children. However, results cannot be extrapolated for children with conductive hearing loss without an accompanying orthodontic indication (maxillary constriction). It showed that the existing prospective studies exhibited qualitative pitfalls, limiting the ability to obtain conclusive evidence about the role of pediatric maxillary expansion on conductive hearing loss in children.

Iron triggers the early stages of cartilage degeneration in vitro: The role of articular chondrocytes.

Objective: Arthropathy is a major clinical problem in patients with hemochromatosis, the most common genetic disorder of iron overload. The pathological features of hemochromatosis arthropathy (HA) are heterogeneous and its specific nature remains unknown. One important drawback is the lack of proper in vitro models. The aim of the present study was to set up a model to investigate the biological response of cartilage to iron exposure. Design: Bovine articular cartilage explants were incubated with ferric citrate for up to 9 days. We evaluated chondrocyte viability, iron deposition, and biomarkers of cartilage degradation in the conditioned medium. Results: Iron accumulated within chondrocytes, which was associated with programmed cell death through chondroptosis. Iron treatment increased the release of sulfated glycosaminoglycans (sGAG), a component of the extracellular matrix, into the medium (p=0.0189). This was dependent on the presence of viable chondrocytes and was associated with increased activity of matrix-degrading metalloproteinases (MMP) (pro/active MMP-9, p=0.0317; pro MMP-2, p=0.0092; active MMP-2, p=0.0288). Co-treatment with the broad MMP/aggrecanase inhibitor prinomastat reduced iron-mediated sGAG release (0.02 â€‹µM, p=0.0425; 2 â€‹µM, p=0.0014), confirming that iron induces sGAG release via the activation of catabolic enzymes. Notably, iron-treated cartilage continued to release an increased amount of sGAG into the medium for 6 days after termination of the ferric citrate treatment (p=0.0259). Conclusions: Iron triggers the early stages of cartilage degeneration. Removal of iron exposure does not prevent further damage to the cartilage, thus providing a possible explanation why HA is not prevented after iron depletion by phlebotomy treatment.

Cell adhesion in microchannel multiple constrictions - Evidence of mass transport limitations.

Biofilm growth (fouling) in microdevices is a critical concern in several industrial, engineering and health applications, particularly in novel high-performance microdevices often designed with complex geometries, narrow regions and multiple headers. Unfortunately, on these devices, the regions with local high wall shear stresses (WSS) also show high local fouling rates. Several explanations have been put forward by the scientific community, including the effect of cell transport by Brownian motion on the adhesion rate. In this work, for the first time, both WSS and convection and Brownian diffusion effects on cell adhesion were evaluated along a microchannel with intercalate constriction and expansion zones designed to mimic the hydrodynamics of the human body and biomedical devices. Convection and Brownian diffusion effects were numerically studied using a steady-state convective-diffusion model (convection, diffusion and sedimentation). According to the numerical results, the convection and Brownian diffusion effects on cell adhesion are effectively more significant in regions with high WSS. Furthermore, a good agreement was observed between experimental and predicted local Sherwood numbers, particularly at the entrance and within the multiple constrictions. However, further mechanisms should be considered to accurately predict cell adhesion in the expansion zones. The described numerical approach can be used as a way to identify possible clogging zones in microchannels, and defining solutions, even before the construction of the prototype.

Lights4Violence: a quasi-experimental educational intervention in six European countries to promote positive relationships among adolescents.

BACKGROUND: Preventing intimate partner violence or dating violence (DV) among adolescents is a public health priority due to its magnitude and damaging short and long-term consequences for adolescent and adult health. In our study protocol, we complement prior experiences in DV prevention by promoting protective factors (or assets) against gender violence such as communication skills, empathy and problem-solving capability through "Cinema Voice", a participatory educational intervention based on adolescents' strengths to tackle DV. METHODS/DESIGN: A longitudinal quasi-experimental educational intervention addressed to boys and girls ages 13-17 years, enrolled in secondary education schools in Alicante (Spain), Rome (Italy), Cardiff (UK), Iasi (Romania), Poznan (Poland) and Matosinhos (Portugal). Both process and results evaluations will be carried out with 100-120 intervention and 120-150 control group students per city at three time periods: before, after and 6 months after the implementation of the following interventions: 1) Training seminar with teachers to promote knowledge and skills on the core issues of intervention; 2) Workshops with intervention groups, where participants produce their own digital content presenting their perspective on DV; and 3) Short film exhibitions with participants, their families, authorities and other stakeholders with the objective of share the results and engage the community. Outcome measures are self-perceived social support, machismo, sexism, tolerance towards gender violence, social problem-solving and assertiveness as well as involvement in bullying/cyberbullying. Other socio-demographic, attitudes and violence-related co-variables were also included. DISCUSSION: This study may provide relevant information about the effectiveness of educational interventions that combine a positive youth development framework with educational awareness about the importance of achieving gender equality and preventing and combating gender violence. To our knowledge, this is the first study that involves six European countries in an educational intervention to promote violence protective assets among enrolled adolescents in secondary schools. This study may provide the needed tools to replicate the experience in other contexts and other countries. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03411564 . Unique Protocol ID: 776905. Date registered: 18-01-2018.

Effects of low-dose intraoperative fentanyl on postoperative respiratory complication rate: a pre-specified, retrospective analysis.

BACKGROUND: Fentanyl is one of the most frequently administered intraoperative drugs and may increase the risk of postoperative respiratory complications (PRCs). METHODS: We performed a pre-specified analysis of 145 735 adult non-cardiac surgical cases under general anaesthesia. Using multivariable logistic regression, we evaluated the association of intraoperative fentanyl dose and PRCs within 3 days after surgery (defined as reintubation, respiratory failure, pneumonia, pulmonary oedema, or atelectasis). We examined effect modification by patient characteristics, surgical site, and anaesthetics used. RESULTS: PRCs within 3 days after surgery occurred in 18 839 (12.9%) patients. In comparison with high intraoperative fentanyl doses [median: 3.85; inter-quartile range (IQR): 3.42-4.50 µg kg-1, quartile 4 (Q4)], low intraoperative fentanyl dose [median: 0.80, IQR: 0.00-1.14 µg kg-1, quartile 1 (Q1)] was significantly associated with lower odds of PRCs [Q1 vs Q4: 10.9% vs 16.2%; adjusted odds ratio (aOR) 0.79; 95% confidence intervals (CI) 0.75-0.84; P<0.001; adjusted absolute risk difference (aARD) -1.7%]. This effect was augmented by thoracic surgery (P for interaction <0.001; aARD -6.2%), high doses of inhalation anaesthetics (P for interaction=0.016; aARD -2.2%) and neuromuscular blocking agents (NMBAs) (P for interaction=0.001; aARD -3.4%). Exploratory analysis demonstrated that compared with no fentanyl, low-dose fentanyl was associated with lower rates of PRCs (decile 2 vs decile 1: aOR 0.82, CI 0.75-0.89, P<0.001). CONCLUSIONS: Intraoperative low-dose fentanyl (about 60-120 µg for a 70 kg patient) was associated with lower risk of postoperative respiratory complications compared with both no fentanyl and high-dose fentanyl. Beneficial effects of low-dose fentanyl were magnified in specific patient subgroups. CLINICAL TRIAL REGISTRATION: NCT03198208.

Role of the impulse oscillometry in the evaluation of tracheal stenosis.

INTRODUCTION AND OBJECTIVES: Tracheal stenosis is a rare and challenging disease. Bronchoscopy is the gold standard for diagnosis and assessment but brings inherent risks. Spirometry is commonly used to access obstructions but is not always feasible due to patient related factors. We therefore considered impulse oscillometry (IOS) as a non-invasive method to quantify airway obstruction and its potential use for diagnosis and follow-up of tracheal stenosis. MATERIALS AND METHODS: Patients with confirmed tracheal stenosis were recruited between January 1st, 2015 and December 31st, 2016. Before bronchoscopy, all subjects underwent IOS and spirometry; for patients submitted to interventional bronchoscopy the same techniques were also performed after the procedure. We assessed the correlation between IOS measurements and airway narrowing as well as between IOS and spirometry values. RESULTS: Twenty-one patients were included. Tracheal narrowing was inversely correlated with X5% (r -0.442, p 0.045) and positively correlated with FEV1/PEF (r 0.467, p 0.033). The stenosis length was inversely correlated with PEF and PEF% (r -0.729, p=0.001 and r -0.707, p=0.002, respectively). There was a strong correlation between spirometric and IOS values. We did not find any significant differences between pre- and post-intervention IOS values for patients assessed after interventional bronchoscopy. CONCLUSIONS: Our study showed a weak correlation between X5% and tracheal narrowing making it unclear whether IOS can be used for physiological assessment of patients with tracheal stenosis. Stenosis length correlated with PEF making it a potential predictor of successful surgical approach. The correlation between IOS and spirometric values makes IOS a potential alternative in patients with suspected tracheal stenosis who are not able to perform spirometry. Larger scale studies should clarify the role of IOS in this pathology.

Transbronchial lung cryobiopsy: Associated complications.

INTRODUCTION: Transbronchial lung cryobiopsy (TBC) has emerged as a diagnostic alternative to surgical lung biopsy in interstitial lung disease (ILD). Despite its less invasive nature, some associated complications have been described. OBJECTIVE: To evaluate complications of TBC and associated factors. METHODS: Prospective evaluation of all patients with ILD submitted to TBC in our centre. Clinicodemographic variables and factors associated to TBC complications were analyzed. The effect of the variables on the complication risk was evaluated by a logistic regression model. RESULTS: Ninety patients were included (mean age 60±13 years; 58.9% male). Twenty-two patients presented pneumothorax, 18 (81.8%) of which were treated with chest tube drainage [median air leak time: 1 day (IQR=2)]. Grade 2 and 3 bleeding was observed in 13 (14.4%) cases. Presence of visceral pleura in the sample accounted for almost more than 10 times the odds of pneumothorax (OR=9.59, 95% CI 2.95-31.17, p<0.001). Increased body mass index (BMI) was associated with bleeding (16% additional odds for each BMI unit increase (OR=1.16, 95% CI 1.01-1.34, p=0.049). CONCLUSION: The most frequent complication of TBC was pneumothorax, although rapidly reversible. There was a positive association between pneumothorax and the presence of pleura in the biopsy samples as well as between bleeding and increased BMI. More studies about TBC complications are needed to improve the selection of the candidates for this procedure.

Idiopathic pulmonary fibrosis in the era of antifibrotic therapy: Searching for new opportunities grounded in evidence.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease that up to now has been associated with a poor prognosis. However, the results of the INPULSIS and ASCEND trials and the approval of nintedanib and pirfenidone have marked the beginning of a new era for IPF patients. Questions remain, however. Should these drugs be used earlier? What effect will they have on more severe disease? Will their effects last beyond the trial period? This manuscript is the outcome of a multidisciplinary meeting between pulmonology, radiology, and pathology clinicians on the use of antifibrotic agents in IPF. In our opinion, the existing data show that pirfenidone and nintedanib slow functional decline in early stages of disease. These drugs also appear to result in therapeutic benefits when administered to patients with advanced disease at diagnosis and maintain effective over time. The data also suggest that continuing antifibrotic therapy after disease progression may confer benefits, but more evidence is needed. Early diagnosis and treatment are crucial for reducing functional decline, slowing disease progression, and improving quality of life.

Prevention of DNA damage and anticarcinogenic activity of Activia® in a preclinical model.

Colorectal cancer is a global public health issue. Studies have pointed to the protective effect of probiotics on colorectal carcinogenesis. Activia® is a lacto probiotic product that is widely consumed all over the world and its beneficial properties are related, mainly, to the lineage of traditional yoghurt bacteria combined with a specific bacillus, DanRegularis, which gives the product a proven capacity to intestinal regulation in humans. The aim of this study was to evaluate the antigenotoxic, antimutagenic, and anticarcinogenic proprieties of the Activia product, in response to damage caused by 1,2-dimethylhydrazine (DMH) in Swiss mice. Activia does not have shown antigenotoxic activity. However, the percent of DNA damage reduction, evaluated by the antimutagenicity assay, ranged from 69.23 to 96.15% indicating effective chemopreventive action. Activia reduced up to 79.82% the induction of aberrant crypt foci by DMH. Facing the results, it is inferred that Activia facilitates the weight loss, prevents DNA damage and pre-cancerous lesions in the intestinal mucosa.

Endobronchial ultrasound-guided transbronchial needle aspiration for nodal staging in non-small cell lung carcinoma.

INTRODUCTION: Lung cancer staging has recently evolved to include endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for nodal assessment. AIM: Evaluate the performance and safety of EBUS-TBNA as a key component of a staging algorithm for non-small cell lung carcinoma (NSCLC) and as a single investigation technique for diagnosis and staging of NSCLC. METHODS: Patients undergoing EBUS-TBNA for NSCLC staging at our institution between April 1, 2010 and December 31, 2014 were consecutively included with prospective data collection. EBUS-TBNA was performed under general anesthesia through a rigid scope. RESULTS: A total of 122 patients, 84.4% males, mean age 64.2 years. Histological type: 78 (63.9%) adenocarcinoma, 33 (27.0%) squamous cell carcinoma, 11 (8.9%) undifferentiated/other NSCLC. A total of 435 lymph node stations were punctured. Median number of nodes per patient was 4. EBUS-TBNA nodal staging: 63 (51.6%) N0; 8 (6.5%) N1; 34 (27.9%) N2, and 17 (13.9%) N3. EBUS-TBNA was the primary diagnostic procedure in 27 (22.1%) patients. EBUS-TBNA NSCLC staging had a sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy rate of 83.3, 100, 100, 86.1, and 91.8%, respectively. No complications were attributable to the procedure. CONCLUSION: A comprehensive lung cancer staging strategy that includes EBUS-TBNA seems to be safe and effective. Our EBUS-TBNA performance and safety in this particular setting was in line with previously published reports. Additionally, our study showed that, in selected patients, lung cancer diagnosis and staging are achievable with a single endoscopic technique.

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.

Discrimination of fast click-series produced by tagged Risso's dolphins (Grampus griseus) for echolocation or communication.

Early studies that categorized odontocete pulsed sounds had few means of discriminating signals used for biosonar-based foraging from those used for communication. This capability to identify the function of sounds is important for understanding and interpreting behavior; it is also essential for monitoring and mitigating potential disturbance from human activities. Archival tags were placed on free-ranging Grampus griseus to quantify and discriminate between pulsed sounds used for echolocation-based foraging and those used for communication. Two types of rapid click-series pulsed sounds, buzzes and burst pulses, were identified as produced by the tagged dolphins and classified using a Gaussian mixture model based on their duration, association with jerk (i.e. rapid change of acceleration) and temporal association with click trains. Buzzes followed regular echolocation clicks and coincided with a strong jerk signal from accelerometers on the tag. They consisted of series averaging 359±210 clicks (mean±s.d.) with an increasing repetition rate and relatively low amplitude. Burst pulses consisted of relatively short click series averaging 45±54 clicks with decreasing repetition rate and longer inter-click interval that were less likely to be associated with regular echolocation and the jerk signal. These results suggest that the longer, relatively lower amplitude, jerk-associated buzzes are used in this species to capture prey, mostly during the bottom phase of foraging dives, as seen in other odontocetes. In contrast, the shorter, isolated burst pulses that are generally emitted by the dolphins while at or near the surface are used outside of a direct, known foraging context.

What are the most important factors determining different vegetation types in the Chapada Diamantina, Brazil? / Quais são os fatores mais importantes na determinação de diferentes tipos de vegetação na Chapada Diamantina, Brasil?

Abstract A transect was used to examine the environmental and biological descriptors of a compact vegetation mosaic in the Chapada Diamantina in northeastern Brazil, including the floristic composition, spectrum of plant life forms, rainfall, and soil properties that defined areas of cerrado (Brazilian savanna), caatinga (seasonally dry tropical forest thorny, deciduous shrub/arboreal vegetation) and cerrado-caatinga transition vegetation. The floristic survey was made monthly from April/2009 to March/2012. A dendrogram of similarity was generated using the Jaccard Index based on a matrix of the species that occurred in at least two of the vegetation types examined. The proportions of life forms in each vegetation type were compared using the chi-square test. Composite soil samples were analyzed by simple variance (ANOVA) to examine relationships between soil parameters of each vegetation type and the transition area. The monthly precipitation levels in each vegetation type were measured and compared using the chi-square test. A total of 323 species of angiosperms were collected distributed in 193 genera and 54 families. The dendrogram demonstrated strong difference between the floristic compositions of the cerrado and caatinga, sharing 2% similarity. The chi-square test did not demonstrate any significant statistical differences between the monthly values of recorded rainfall. The organic matter and clay contents of the soilsin the caatinga increased while sand decreased, and the proportions of therophyte, hemicryptophyte, and chamaephyte life forms decreased and phanerophytes increased. We can therefore conclude that the floristic composition and the spectrum of life forms combined to define the cerrado and caatinga vegetation along the transect examined, with soil being the principal conditioning factor determining the different vegetation types, independent of precipitation levels.

Resumo Foi estabelecida uma transecção para examinar descritores ambientais e biológicos em uma área compacta de vegetação em mosaico na Chapada Diamantina, Nordeste do Brasil. A composição florística, espectro de formas de vida, precipitação e propriedades do solo foram avaliadas na transecção entre cerrado (savana brasileira) e caatinga (floresta tropical sazonalmente seca espinhosa, vegetação arbustivo-arbórea decídua), separados por vegetação de transição cerrado-caatinga. O levantamento florístico foi realizado mensalmente de abril de 2009 a março de 2012. Foi feita análise de agrupamento a fim de determinar a similaridade entre as fisionomias de cerrado, a caatinga e a transição cerrado-caatinga. As proporções de formas de vida foram comparadas utilizando o teste qui-quadrado. Amostras compostas de solo foram analisadas por variância simples (ANOVA) testando a existência de diferenças entre os solos de cada tipo de vegetação. A precipitação mensal em cada tipo de vegetação foi mensurada e os resultados comparados com o teste qui-quadrado. Coletamos 323 espécies de angiospermas pertencentes a 193 gêneros e 54 famílias. A análise de agrupamento demostrou diferença entre a composição florística do cerrado e da caatinga, com apenas 2% de similaridade. O teste qui-quadrado não demonstrou diferença estatística entre os valores registrados para cada mês. À medida que os conteúdos de matéria orgânica e argila aumentaram e o de areia diminuiu na caatinga, a proporção das formas de vida terófito, hemicriptófito e caméfito diminuiu e a de fanerófitos aumentou. Podemos considerar que a composição florística e o espectro de formas de vida delimitaram o cerrado e a caatinga na transecção estudada e que o solo foi o principal fator condicionante para determinação dos diferentes tipos de vegetação, independentemente da precipitação.

What are the most important factors determining different vegetation types in the Chapada Diamantina, Brazil?

A transect was used to examine the environmental and biological descriptors of a compact vegetation mosaic in the Chapada Diamantina in northeastern Brazil, including the floristic composition, spectrum of plant life forms, rainfall, and soil properties that defined areas of cerrado (Brazilian savanna), caatinga (seasonally dry tropical forest thorny, deciduous shrub/arboreal vegetation) and cerrado-caatinga transition vegetation. The floristic survey was made monthly from April/2009 to March/2012. A dendrogram of similarity was generated using the Jaccard Index based on a matrix of the species that occurred in at least two of the vegetation types examined. The proportions of life forms in each vegetation type were compared using the chi-square test. Composite soil samples were analyzed by simple variance (ANOVA) to examine relationships between soil parameters of each vegetation type and the transition area. The monthly precipitation levels in each vegetation type were measured and compared using the chi-square test. A total of 323 species of angiosperms were collected distributed in 193 genera and 54 families. The dendrogram demonstrated strong difference between the floristic compositions of the cerrado and caatinga, sharing 2% similarity. The chi-square test did not demonstrate any significant statistical differences between the monthly values of recorded rainfall. The organic matter and clay contents of the soilsin the caatinga increased while sand decreased, and the proportions of therophyte, hemicryptophyte, and chamaephyte life forms decreased and phanerophytes increased. We can therefore conclude that the floristic composition and the spectrum of life forms combined to define the cerrado and caatinga vegetation along the transect examined, with soil being the principal conditioning factor determining the different vegetation types, independent of precipitation levels.