Experiences and mediating factors in nurses' responses to electronic device alarms: A phenomenological study.

AIM: This study aims to explore the experiences and mediating factors of nurses' responses to electronic device alarms in critical care units (CCUs). BACKGROUND: Alarm fatigue occasionally has adverse consequences for patient safety. METHODS: This qualitative study was designed and analysed following Giorgi's descriptive phenomenological approach. Seventeen nurses were theoretically sampled, reaching information saturation. Semistructured interviews were used to collect the data. RESULTS: Three central themes explained nurses' experiences: general perceptions about alarms (basic equipment of the CCU), strategies to reduce false alarms (training in the configuration of monitors, customization of the alarms to fit he patient's condition. teamwork and taking advantage of the development of technology) and key elements of the response to alarms (information about patient's condition, nurses' clinical experience, type of CCU, 'cry-wolf' phenomenon and nurse/patient ratio). CONCLUSIONS: To reduce false alarms, nurses need further postgraduate training, training on monitors and customizing alarms to fit the patient's health status. The complex process of deciding to respond to an alarm includes environmental, professional variables and patient status. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should ensure that nurses have sufficient experience and training in the CCU, improve the nurse/patient ratio, promote teamwork and ensure that the devices are the latest generation.

Pre- and post-junctional bradykinin B2 receptors regulate smooth muscle tension to the pig intravesical ureter.

AIMS: Neuronal and non-neuronal bradykinin (BK) receptors regulate the contractility of the bladder urine outflow region. The current study investigates the role of BK receptors in the regulation of the smooth muscle contractility of the pig intravesical ureter. METHODS: Western blot and immunohistochemistry were used to show the expression of BK B1 and B2 receptors and myographs for isometric force recordings. RESULTS: B2 receptor expression was consistently detected in the intravesical ureter urothelium and smooth muscle layer, B1 expression was not detected where a strong B2 immunoreactivity was observed within nerve fibers among smooth muscle bundles. On ureteral strips basal tone, BK induced concentration-dependent contractions, were potently reduced by extracellular Ca(2+) removal and by B2 receptor and voltage-gated Ca(2+) (VOC) channel blockade. BK contraction did not change as a consequence of urothelium mechanical removal or cyclooxygenase and Rho-associated protein kinase inhibition. On 9,11-dideoxy-9a,11a-methanoepoxy prostaglandin F2α (U46619)-precontracted samples, under non-adrenergic non-cholinergic (NANC) and nitric oxide (NO)-independent NANC conditions, electrical field stimulation-elicited frequency-dependent relaxations which were reduced by B2 receptor blockade. Kallidin, a B1 receptor agonist, failed to increase preparation basal tension or to induce relaxation on U46619-induced tone. CONCLUSIONS: The present results suggest that BK produces contraction of pig intravesical ureter via smooth muscle B2 receptors coupled to extracellular Ca(2+) entry mainly via VOC (L-type) channels. Facilitatory neuronal B2 receptors modulating NO-dependent or independent NANC inhibitory neurotransmission are also demonstrated.

Fatty acid and phospholipid biosynthetic pathways are regulated throughout mammary epithelial cell differentiation and correlate to breast cancer survival.

This work combined gene and protein expression, gas chromatography-flame ionization detector, and hydrophilic interaction liquid chromatography-tandem mass spectrometry to compare lipid metabolism changes in undifferentiated/proliferating vs. functionally differentiated mammary epithelial cells (MECs) and to study their correlation to breast cancer survival. Sixty-eight genes involved in lipid metabolism were changed in MEC differentiation. Differentiated cells showed induction of Elovl6 (2-fold), Scd1 (4-fold), and Fads2 (2-fold), which correlated with increased levels of C16:1 n-7 and C18:1 n-9 (1.5-fold), C20:3 n-6 (2.5-fold), and C20:4 n-6 (6-fold) fatty acids (FAs) and more phospholipids (PLs) containing these species. Further, increased expression (2- to 3-fold) of genes in phosphatidylethanolamine (PE) de novo biosynthesis resulted in a 20% PE increase. Proliferating/undifferentiated cells showed higher C16:0 (1.7-fold) and C18:2 n-6 (4.2-fold) levels and more PLs containing C16:0 FAs [PC(16:0/16:1), PG(16:0/18:2), PG(16:0/18:1), and SM(16:0/18:0)]. Kaplan-Meier analysis of data from 3455 patients with breast cancer disclosed a positive correlation for 59% of genes expressed in differentiated MECs with better survival. PE biosynthesis and FA oxidation correlated with better prognosis in patients with breast cancer, including the basal-like subtype. Therefore, genes involved in mammary gland FA and PL metabolism and their resulting molecular species reflect the cellular proliferative ability and differentiation state and deserve further studies as potential markers of breast cancer progression

Powerful relaxation of phosphodiesterase type 4 inhibitor rolipram in the pig and human bladder neck.

INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors act as effective drugs for the treatment of lower urinary tract symptom (LUTS). There is a poor information, however, about the role of the PDE4 inhibitors on the bladder outflow region contractility. AIM: To investigate PDE4 expression and the relaxation induced by the PDE4 inhibitor rolipram versus that induced by the PDE5 blockers sildenafil and vardenafil, in the pig and human bladder neck. METHODS: Immunohistochemistry for PDE4 expression, myographs for isometric force recordings and fura-2 fluorescence for simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i ) and tension for rolipram in bladder neck samples were used. MAIN OUTCOME MEASURES: PDE4 expression and relaxations to PDE4 and PDE5 inhibitors and simultaneous measurements of [Ca2+]i and tension. RESULTS: PDE4 expression was observed widely distributed in the smooth muscle layer of the pig and human bladder neck. On urothelium-denuded phenylephrine (PhE)-precontracted strips of pig and human, rolipram, sildenafil and vardenafil produced concentration-dependent relaxations with the following order of potency: rolipram> > sildenafil>vardenafil. In pig, the adenylyl cyclase activator forskolin potentiated rolipram-elicited relaxation, whereas protein kinase A (PKA) blockade reduced such effect. On potassium-enriched physiological saline solution (KPSS)-precontracted strips, rolipram evoked a lower relaxation than that obtained on PhE-stimulated preparations. Inhibition of large (BKCa ) and intermediate (IKCa ) conductance Ca2+ -activated K+ channels, neuronal voltage-gated Ca2+ channels, nitric oxide (NO) and hydrogen sulfide (H2 S) synthases reduced rolipram responses. Rolipram inhibited the contractions induced by PhE without reducing the PhE-evoked [Ca2+]i increase. CONCLUSIONS: PDE4 is present in the pig and human bladder neck smooth muscle, where rolipram exerts a much more potent relaxation than that elicited by PDE5 inhibitors. In pig, rolipram-induced response is produced through the PKA pathway involving BKCa and IKCa channel activation and [Ca2+]i desensitization-dependent mechanisms, this relaxation also being due to neuronal NO and H2S release.

Neuronal and non-neuronal bradykinin receptors are involved in the contraction and/or relaxation to the pig bladder neck smooth muscle.

AIMS: The current study investigates the role played by bradykinin (BK) receptors in the contractility to the pig bladder neck smooth muscle. METHODS: Bladder neck strips were mounted in myographs for isometric force recordings and BK receptors expression was also determined by immunohistochemistry. RESULTS: B2 receptor expression was observed in the muscular layer and urothelium whereas B1 expression was consistent detected in urothelium. A strong B2 immunoreactivity was also observed within nerve fibers among smooth muscle bundles. On urothelium-denuded preparations basal tone, BK induced concentration-dependent contractions which were reduced in urothelium-intact samples, by extracellular Ca(2+) removal and by blockade of B2 receptors and voltage-gated Ca(2+) (VOC) and non-VOC channels, and increased by cyclooxygenase (COX) inhibition. On phenylephrine-precontracted denuded strips, under non-adrenergic non-cholinergic (NANC) conditions, electrical field stimulation-elicited frequency-dependent relaxations which were reduced by B2 receptor blockade. In urothelium-intact samples, the B1 receptor agonist kallidin promoted concentration-dependent relaxations which were reduced by blockade of B1 receptors, COX, COX-1 and large-conductance Ca(2+) -activated K(+) (BKCa ) channels and abolished in urothelium-denuded samples and in K(+) -enriched physiological saline solution-precontracted strips. CONCLUSIONS: These results suggest that BK produces contraction of pig bladder neck via smooth muscle B2 receptors coupled to extracellular Ca(2+) entry via VOC and non-VOC channels with a minor role for intracellular Ca(2+) mobilization. Facilitatory neuronal B2 receptors modulating NANC inhibitory neurotransmission and urothelial B1 receptors producing relaxation via the COX-1 pathway and BKCa channel opening are also demonstrated. Neurourol. Urodynam. 33:558-565, 2014. © 2013 Wiley Periodicals, Inc.

Biomechanical Factors Predisposing to Knee Injuries in Junior Female Basketball Players.

This cross-sectional observational study aims to determine isokinetic normality data at different speeds, and isometric data of ankle and knee joints, in healthy basketball players aged 15-16 years old. The participants were recruited through non-probabilistic convenience sampling. Sociodemographic, anthropometric, and biomechanical variables were collected. The study involved 42 participants. Right-leg dominance was higher in women (85.7%) than in men (78.6%). Men had a higher weight, height, and body mass index compared to women. Statistically significant differences were observed between sex and height (p < 0.001). Significant differences were found between sexes in knee flexor and extensor strength at different isokinetic speeds (30°, 120°, and 180°/s), except for the maximum peak strength knee flexion at 180°/s in the right leg. In the ankle, the variables inversion, eversion, and work strength values at different isokinetic speeds and full RoM, by sex, were not significantly different, except for the right (p = 0.004) and the left (p = 0.035) ankle full RoM. The study found lower knee extensor strength in women, indicating the need to improve knee flexor/extensor strength in women to match that of men, as seen in other joints. The results can guide the development of preventive and therapeutic interventions for lower limb injuries in basketball players.

CLMP is required for intestinal development, and loss-of-function mutations cause congenital short-bowel syndrome.

BACKGROUND & AIMS: Short-bowel syndrome usually results from surgical resection of the small intestine for diseases such as intestinal atresias, volvulus, and necrotizing enterocolitis. Patients with congenital short-bowel syndrome (CSBS) are born with a substantial shortening of the small intestine, to a mean length of 50 cm, compared with a normal length at birth of 190-280 cm. They also are born with intestinal malrotation. Because CSBS occurs in many consanguineous families, it is considered to be an autosomal-recessive disorder. We aimed to identify and characterize the genetic factor causing CSBS. METHODS: We performed homozygosity mapping using 610,000 K single-nucleotide polymorphism arrays to analyze the genomes of 5 patients with CSBS. After identifying a gene causing the disease, we determined its expression pattern in human embryos. We also overexpressed forms of the gene product that were and were not associated with CSBS in Chinese Hamster Ovary and T84 cells and generated a zebrafish model of the disease. RESULTS: We identified loss-of-function mutations in Coxsackie- and adenovirus receptor-like membrane protein (CLMP) in CSBS patients. CLMP is a tight-junction-associated protein that is expressed in the intestine of human embryos throughout development. Mutations in CLMP prevented its normal localization to the cell membrane. Knock-down experiments in zebrafish resulted in general developmental defects, including shortening of the intestine and the absence of goblet cells. Because goblet cells are characteristic for the midintestine in zebrafish, which resembles the small intestine in human beings, the zebrafish model mimics CSBS. CONCLUSIONS: Loss-of-function mutations in CLMP cause CSBS in human beings, likely by interfering with tight-junction formation, which disrupts intestinal development. Furthermore, we developed a zebrafish model of CSBS.

Hydrogen sulfide mediated inhibitory neurotransmission to the pig bladder neck: role of KATP channels, sensory nerves and calcium signaling.

PURPOSE: Because neuronal released endogenous H2S has a key role in relaxation of the bladder outflow region, we investigated the mechanisms involved in H2S dependent inhibitory neurotransmission to the pig bladder neck. MATERIALS AND METHODS: Bladder neck strips were mounted in myographs for isometric force recording and simultaneous measurement of intracellular Ca(2+) and tension. RESULTS: On phenylephrine contracted preparations electrical field stimulation and the H2S donor GYY4137 evoked frequency and concentration dependent relaxation, which was reduced by desensitizing capsaicin sensitive primary afferents with capsaicin, and the blockade of adenosine 5'-triphosphate dependent K(+) channels, cyclooxygenase and cyclooxygenase-1 with glibenclamide, indomethacin and SC560, respectively. Inhibition of vanilloid, transient receptor potential A1, transient receptor potential vanilloid 1, vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide and calcitonin gene-related peptide receptors with capsazepine, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively, also decreased electrical field stimulation and GYY4137 responses. H2S relaxation was not changed by guanylyl cyclase, protein kinase A, or Ca(2+) activated or voltage gated K(+) channel inhibitors. GYY4137 inhibited the contractions induced by phenylephrine and by K(+) enriched (80 mM) physiological saline solution. To a lesser extent it decreased the phenylephrine and K(+) induced increases in intracellular Ca(2+). CONCLUSIONS: H2S produces pig bladder neck relaxation via activation of adenosine 5'-triphosphate dependent K(+) channel and by smooth muscle intracellular Ca(2+) desensitization dependent mechanisms. H2S also promotes the release of sensory neuropeptides and cyclooxygenase-1 pathway derived prostanoids from capsaicin sensitive primary afferents via transient receptor potential A1, transient receptor potential vanilloid 1 and/or related ion channel activation.

Endogenous hydrogen sulfide has a powerful role in inhibitory neurotransmission to the pig bladder neck.

PURPOSE: We investigated the possible involvement of H2S in nitric oxide independent inhibitory neurotransmission to the pig bladder neck. MATERIALS AND METHODS: We used immunohistochemistry to determine the expression of the H2S synthesis enzymes cystathionine γ-lyase and cystathionine ß-synthase. We also used electrical field stimulation and myographs for isometric force recordings to study relaxation in response to endogenously released or exogenously applied H2S in urothelium denuded, phenylephrine precontracted bladder neck strips under noradrenergic, noncholinergic, nonnitrergic conditions. RESULTS: Cystathionine γ-lyase and cystathionine ß-synthase expression was observed in nerve fibers in the smooth muscle layer. Cystathionine γ-lyase and cystathionine ß-synthase immunoreactive fibers were also identified around the small arteries supplying the bladder neck. Electrical field stimulation (2 to 16 Hz) evoked frequency dependent relaxation, which was decreased by DL-propargylglycine and abolished by tetrodotoxin (blockers of cystathionine γ-lyase and neuronal voltage gated Na(+) channels, respectively). The cystathionine ß-synthase inhibitor O-(carboxymethyl)hydroxylamine did not change nerve mediated responses. The H2S donor GYY4137 (0.1 nM to 10 µM) induced potent, concentration dependent relaxation, which was not modified by neuronal voltage gated Na(+) channels, or cystathionine γ-lyase or cystathionine ß-synthase blockade. CONCLUSIONS: Results suggest that endogenous H2S synthesized by cystathionine γ-lyase and released from intramural nerves acts as a powerful signaling molecule in nitric oxide independent inhibitory transmission to the pig bladder neck.

Rectal Bezoar: A Rare Cause of Intestinal Obstruction.

Bezoars are conglomerates of undigested contents that accumulate in the gastrointestinal tract. They can have different compositions, such as fibers, seeds, vegetables (phytobezoars), hair (trichobezoars), and medication (pharmacobezoars). Bezoars are typically caused by an impaired grinding mechanism of the stomach or interdigestive migrating motor complex, but the composition of ingested material can also play a role in their formation. Gastric dysmotility, previous gastric surgery, and gastroparesis are some of the risk factors that can increase the likelihood of developing bezoars. While bezoars are usually asymptomatic and found in the stomach, they can sometimes migrate to the small intestine or colon and cause complications such as intestinal obstruction or perforation. Endoscopy is essential for diagnosis and etiology, and treatment depends on the composition, which can include chemical dissolution or surgical intervention. We present a case of an 86-year-old woman, who had a bezoar located in an unusual location (rectum), most likely due to migration. This condition led to symptoms of intermittent intestinal obstruction and rectal bleeding. However, due to anal stenosis, the patient was unable to expel the bezoar. Its removal was not possible through various endoscopic techniques. Therefore, it was removed via fragmentation, using an anoscope and forceps, due to its hard/stone-like consistency. This case highlights the importance of considering bezoars in the differential diagnosis of gastrointestinal bleeding and illustrates the importance of prompt diagnosis and appropriate techniques for the removal of bezoars.

Biomechanical analysis of barefoot walking and three different sports footwear in children aged between 4 and 6 years old.

The technological transformation and advertising utilized in the footwear industry significantly impact purchasing decisions. The gait properties, barefoot and with shoes, change depending on the footwear structure. The aim of this work is the biomechanical analysis of walking barefoot and with different sports shoes in a controlled group of 12 children between 4 and 6 years old. Kinematic and spatiotemporal variables were analyzed using a BTS motion capture analysis system with the Helen Hayes protocol. Previously, a survey was carried out with 262 families with children between 4 and 6 years old to justify the choice of footwear for this study. No significant differences were found between any of the measured conditions. The kinematic results showed significant differences in the ankle (right sagittal plane p = 0.04, left p < 0.01; right frontal plane p < 0.01, left p < 0.01), knee (right and left sagittal plane p < 0.01) and hip (right sagittal plane p < 0.01, left p = 0.04; right frontal plane p = 0.03). Additionally, the post hoc analysis revealed significant differences between barefoot gait and different footwear. The footwear used for this study and each one's various characteristics are not preponderant in the spatiotemporal and kinematic parameters of the children's gait. Thus, the footwear purchase may be conditioned by its design or composition and other properties may not be relevant.

Mechanisms involved in endothelin-1-induced contraction of the pig urinary bladder neck.

AIMS: There is no information about the signaling pathways involved in the endothelin-1 (ET-1)-induced contraction of bladder neck. The current study investigates the mechanisms involved in the ET-1-elicited contraction in the pig bladder neck. METHODS: Bladder neck strips were mounted in organ baths containing physiological saline solution at 37°C and gassed with 95% O(2) and 5% CO(2) , for isometric force recording to endothelin receptor agonists, noradrenaline (NA), and electrical field stimulation. Endothelin ET(A) receptor expression was also determined, by both immunohistochemistry and Western blot. RESULTS: ET(A) receptor expression (Western blot) was observed in the muscular layer and urothelium. A strong ET(A) -immunoreactivity (ET(A) -IR) was identified within nerve fibers among smooth muscle bundles. ET-1 and ET-2 evoked similar concentration-dependent contractions of urothelium-denuded preparations. ET-3 produced a slight response, whereas the ET(B) receptor agonist BQ3020 failed to promote contraction. BMS182874, an ET(A) receptor antagonist, reduced ET-1-induced contraction whereas BQ788, an ET(B) antagonist, did not change such responses. ET-1 contractions were reduced by extracellular Ca(2+) removal and by inhibition of voltage-gated Ca(2+) (VOC) (L-type) and non-VOC channels, Rho/Rho-kinase pathway, and neuronal VOC channels. NA produced contractions which were enhanced by ET-1 threshold concentrations. ET(A) receptor blockade enhanced nitric oxide-dependent nerve-mediated relaxations. CONCLUSIONS: These results suggest that ET-1 produces contraction via muscular ET(A) receptors coupled to extracellular Ca(2+) entry via VOC (L-type) and non-VOC channels. Intracellular Ca(2+) mobilization and a Rho/Rho-kinase pathway could also be involved in these responses. ET-1-evoked potentiation on noradrenergic contraction, and neuronal ET(A) receptors modulating nitrergic inhibitory neurotransmission, are also demonstrated.

Cadherin-3 is a novel oncogenic biomarker with prognostic value in glioblastoma.

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. The prognosis of patients is very poor, with a median overall survival of ~ 15 months after diagnosis. Cadherin-3 (also known as P-cadherin), a cell-cell adhesion molecule encoded by the CDH3 gene, is deregulated in several cancer types, but its relevance in GBM is unknown. In this study, we investigated the functional roles, the associated molecular signatures, and the prognostic value of CDH3/P-cadherin in this highly malignant brain tumor. CDH3/P-cadherin mRNA and protein levels were evaluated in human glioma samples. Knockdown and overexpression models of P-cadherin in GBM were used to evaluate its functional role in vitro and in vivo. CDH3-associated gene signatures were identified by enrichment analyses and correlations. The impact of CDH3 in the survival of GBM patients was assessed in independent cohorts using both univariable and multivariable models. We found that P-cadherin protein is expressed in a subset of gliomas, with an increased percentage of positive samples in grade IV tumors. Concordantly, CDH3 mRNA levels in glioma samples from The Cancer Genome Atlas (TCGA) database are increased in high-grade gliomas. P-cadherin displays oncogenic functions in multiple knockdown and overexpression GBM cell models by affecting cell viability, cell cycle, cell invasion, migration, and neurosphere formation capacity. Genes that were positively correlated with CDH3 are enriched for oncogenic pathways commonly activated in GBM. In vivo, GBM cells expressing high levels of P-cadherin generate larger subcutaneous tumors and cause shorter survival of mice in an orthotopic intracranial model. Concomitantly, high CDH3 expression is predictive of shorter overall survival of GBM patients in independent cohorts. Together, our results show that CDH3/P-cadherin expression is associated with aggressiveness features of GBM and poor patient prognosis, suggesting that it may be a novel therapeutic target for this deadly brain tumor.

Mechanisms involved in the adenosine-induced vasorelaxation to the pig prostatic small arteries.

Benign prostatic hypertrophy has been related with glandular ischemia processes and adenosine is a potent vasodilator agent. This study investigates the mechanisms underlying the adenosine-induced vasorelaxation in pig prostatic small arteries. Adenosine receptors expression was determined by Western blot and immunohistochemistry, and rings were mounted in myographs for isometric force recording. A(2A) and A(3) receptor expression was observed in the arterial wall and A(2A)-immunoreactivity was identified in the adventitia-media junction and endothelium. A(1) and A(2B) receptor expression was not obtained. On noradrenaline-precontracted rings, P1 receptor agonists produced concentration-dependent relaxations with the following order of potency: 5'-N-ethylcarboxamidoadenosine (NECA) = CGS21680 > 2-Cl-IB-MECA = 2-Cl-cyclopentyladenosine = adenosine. Adenosine reuptake inhibition potentiated both NECA and adenosine relaxations. Endothelium removal and ZM241385, an A(2A) antagonist, reduced NECA relaxations that were not modified by A(1), A(2B), and A(3) receptor antagonists. Neuronal voltage-gated Ca(2+) channels and nitric oxide (NO) synthase blockade, and adenylyl cyclase activation enhanced these responses, which were reduced by protein kinase A inhibition and by blockade of the intermediate (IK(Ca))- and small (SK(Ca))-conductance Ca(2+)-activated K(+) channels. Inhibition of cyclooxygenase (COX), large-conductance Ca(2+)-activated-, ATP-dependent-, and voltage-gated-K(+) channel failed to modify these responses. These results suggest that adenosine induces endothelium-dependent relaxations in the pig prostatic arteries via A(2A) purinoceptors. The adenosine vasorelaxation, which is prejunctionally modulated, is produced via NO- and COX-independent mechanisms that involve activation of IK(Ca) and SK(Ca) channels and stimulation of adenylyl cyclase. Endothelium-derived NO playing a regulatory role under conditions in which EDHF is non-functional is also suggested. Adenosine-induced vasodilatation could be useful to prevent prostatic ischemia.

Radiation exposure awareness from patients undergoing nuclear medicine diagnostic 99mTc-MDP bone scans and 2-deoxy-2-(18F) fluoro-D-glucose PET/computed tomography scans.

INTRODUCTION: Medical imaging is on average the largest source of artificial radiation exposure worldwide. This study seeks to understand patient's awareness of radiation exposure derived from nuclear medicine diagnostic scans and assess if current information provided by leaflets is adequate. METHODS: Single-centre cross-sectional questionnaire study applied to bone scan and FDG PET/computed tomography patients, at a nuclear medicine and PET/computed tomography department over a 15-week period in 2018. Questionnaires on dose comparators were designed in collaboration with patients, public, and experts in radiation exposure. Qualitative data were analysed using thematic analysis and quantitative data using SPSS (V. 24). RESULTS: A total of 102 questionnaires were completed (bone scan = 50; FDG PET/computed tomography = 52). Across both groups, 33/102 (32.4%) patients reported having a reasonable understanding of nuclear medicine and 21/102 (20.6%) reported a reasonable knowledge of ionising radiations. When asked to compare the exposure dose of respective scans with common comparators 8/50 (16%) of bone scan patients and 11/52 (21.2%) FDG PET/computed tomography answered correctly. On leaflet information, 15/85 (17.6%) patients reported the leaflets do not provide enough information on radiation exposure and of these 10/15 (66.7%) commented the leaflets should incorporate more information on radiation exposure dose. CONCLUSION: More observational and qualitative studies in collaboration with patients are warranted to evaluate patients' understanding and preferences in communication of radiation exposure from nuclear medicine imaging. This will ensure communication tools and guidelines developed to comply with ionising radiation (medical exposure) regulation 2017 are according to patients needs and preferences.

Evaluation of AAV-mediated delivery of shRNA to target basal-like breast cancer genetic vulnerabilities.

Adeno-associated viral vectors (AAV) for gene therapy applications are gaining momentum, with more therapies moving into later stages of clinical development and towards market approval, namely for cancer therapy. The development of cytotoxic vectors is often hampered by side effects arising when non-target cells are infected, and their production can be hindered by toxic effects of the transgene on the producing cell lines. In this study, we evaluated the potential of rAAV-mediated delivery of short hairpin RNAs (shRNA) to target basal-like breast cancer genetic vulnerabilities. Our results show that by optimizing the stoichiometry of the plasmids upon transfection and time of harvest, it is possible to increase the viral titers and quality. All rAAV-shRNA vectors obtained efficiently transduced the BLBC cell lines MDA-MB-468 and HCC1954. In MDA-MB-468, transduction with rAAV-shRNA vector targeting PSMA2 was associated with significant decrease in cell viability and apoptosis induction. Importantly, rAAV2-PSMA2 also slowed tumor growth in a BLBC mouse xenograft model, thus potentially representing a therapeutic strategy against this type of cancer.

Silk-based anisotropical 3D biotextiles for bone regeneration.

Bone loss in the craniofacial complex can been treated using several conventional therapeutic strategies that face many obstacles and limitations. In this work, novel three-dimensional (3D) biotextile architectures were developed as a possible strategy for flat bone regeneration applications. As a fully automated processing route, this strategy as potential to be easily industrialized. Silk fibroin (SF) yarns were processed into weft-knitted fabrics spaced by a monofilament of polyethylene terephthalate (PET). A comparative study with a similar 3D structure made entirely of PET was established. Highly porous scaffolds with homogeneous pore distribution were observed using micro-computed tomography analysis. The wet state dynamic mechanical analysis revealed a storage modulus In the frequency range tested, the storage modulus values obtained for SF-PET scaffolds were higher than for the PET scaffolds. Human adipose-derived stem cells (hASCs) cultured on the SF-PET spacer structures showed the typical pattern for ALP activity under osteogenic culture conditions. Osteogenic differentiation of hASCs on SF-PET and PET constructs was also observed by extracellular matrix mineralization and expression of osteogenic-related markers (osteocalcin, osteopontin and collagen type I) after 28 days of osteogenic culture, in comparison to the control basal medium. The quantification of convergent macroscopic blood vessels toward the scaffolds by a chick chorioallantoic membrane assay, showed higher angiogenic response induced by the SF-PET textile scaffolds than PET structures and gelatin sponge controls. Subcutaneous implantation in CD-1 mice revealed tissue ingrowth's accompanied by blood vessels infiltration in both spacer constructs. The structural adaptability of textile structures combined to the structural similarities of the 3D knitted spacer fabrics to craniofacial bone tissue and achieved biological performance, make these scaffolds a possible solution for tissue engineering approaches in this area.

Modulating cell adhesion to polybutylene succinate biotextile constructs for tissue engineering applications.

Textile-based technologies are powerful routes for the production of three-dimensional porous architectures for tissue engineering applications because of their feasibility and possibility for scaling-up. Herein, the use of knitting technology to produce polybutylene succinate fibre-based porous architectures is described. Furthermore, different treatments have been applied to functionalize the surface of the scaffolds developed: sodium hydroxide etching, ultraviolet radiation exposure in an ozone atmosphere and grafting (acrylic acid, vinyl phosphonic acid and vinyl sulphonic acid) after oxygen plasma activation as a way to tailor cell adhesion. A possible effect of the applied treatments on the bulk properties of the textile scaffolds has been considered and thus tensile tests in dry and hydrated states were also carried out. The microscopy results indicated that the surface morphology and roughness were affected by the applied treatments. The X-ray photoelectron spectroscopy and contact angle measurements showed the incorporation of oxygen-containing groups and higher surface free energy as result of the surface treatments applied. The DNA quantification and scanning electron microscopy analysis revealed that these modifications enhanced cell adhesion and altered cell morphology. Generally, sodium hydroxide treatment altered most significantly the surface properties, which in turn resulted in a high number of cells adherent to these surfaces. Based on the results obtained, the proposed surface treatments are appropriate to modify polybutylene succinate knitting scaffolds, influencing cell adhesion and its potential for use in tissue engineering applications. Copyright © 2016 John Wiley & Sons, Ltd.

Impaired Excitatory Neurotransmission in the Urinary Bladder from the Obese Zucker Rat: Role of Cannabinoid Receptors.

Metabolic syndrome (MS) is a known risk factor for lower urinary tract symptoms. This study investigates whether functional and expression changes of cannabinoid CB1 and CB2 receptors are involved in the bladder dysfunction in an obese rat model with insulin resistance. Bladder samples from obese Zucker rat (OZR) and their respective controls lean Zucker rat (LZR) were processed for immunohistochemistry and western blot for studying the cannabinoid receptors expression. Detrusor smooth muscle (DSM) strips from LZR and OZR were also mounted in myographs for isometric force recordings. Neuronal and smooth muscle CB1 and CB2 receptor expression and the nerve fiber density was diminished in the OZR bladder. Electrical field stimulation (EFS) and acetylcholine (ACh) induced frequency- and concentration-dependent contractions of LZR and OZR DSM. ACh contractile responses were similar in LZR and OZR. EFS-elicited contractions, however, were reduced in OZR bladder. Cannabinoid receptor agonists and antagonists failed to modify the DSM basal tension in LZR and OZR In LZR bladder, EFS responses were inhibited by ACEA and SER-601, CB1 and CB2 receptor agonists, respectively, these effects being reversed by ACEA plus the CB1 antagonist, AM-251 or SER-601 plus the CB2 antagonist, AM-630. In OZR bladder, the inhibitory action of ACEA on nerve-evoked contractions was diminished, whereas that SER-601 did not change EFS responses. These results suggest that a diminished function and expression of neuronal cannabinoid CB1 and CB2 receptors, as well as a lower nerve fiber density is involved in the impaired excitatory neurotransmission of the urinary bladder from the OZR.

Influence of different surface modification treatments on silk biotextiles for tissue engineering applications.

Biotextile structures from silk fibroin have demonstrated to be particularly interesting for tissue engineering (TE) applications due to their high mechanical strength, interconnectivity, porosity, and ability to degrade under physiological conditions. In this work, we described several surface treatments of knitted silk fibroin (SF) scaffolds, namely sodium hydroxide (NaOH) solution, ultraviolet radiation exposure in an ozone atmosphere (UV/O3) and oxygen (O2) plasma treatment followed by acrylic acid (AAc), vinyl phosphonic acid (VPA), and vinyl sulfonic acid (VSA) immersion. The effect of these treatments on the mechanical properties of the textile constructs was evaluated by tensile tests in dry and hydrated states. Surface properties such as morphology, topography, wettability and elemental composition were also affected by the applied treatments. The in vitro biological behavior of L929 fibroblasts revealed that cells were able to adhere and spread both on the untreated and surface-modified textile constructs. The applied treatments had different effects on the scaffolds' surface properties, confirming that these modifications can be considered as useful techniques to modulate the surface of biomaterials according to the targeted application.