Influence of levofloxacin and clarithromycin on the structure of DPPC monolayers

Research on lipid/drug interactions at the nanoscale underpins the emergence of synergistic mechanisms for topical drug administration. The structural understanding of bio-mimetic systems employing 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as a lung surfactant model mixed with antibiotics, as well as their biophysical properties, is of critical importance to modulate the effectiveness of therapeutic agents released directly to the airways. In this paper, we investigate the structural details of the interaction between Levofloxacin, ‘a respiratory quinolone’, and the macrolide Clarithromycin, with DPPC monolayers at the air-water interface, using a combination of Brewster angle microscopy, polarization modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS), surface pressure isotherms and neutron reflectometry (NR) to describe the structural details of this interaction. The results allowed association of changes in the π-A isotherm profile with changes in the molecular organization and the co-localization of the antibiotics within the lipid monolayer by NR measurements. Overall, both antibiotics are able to increase the thickness of the acyl tails in DPPC monolayers with a corresponding reduction in tail tilt as well as to interact with the phospholipid headgroups as shown by PM-IRRAS experiments. The effects on the DPPC monolayers are correlated with the physical-chemical properties of each antibiotic and dependent on its concentration

Differential cellular FGF-2 upregulation in the rat facial nucleus following axotomy, functional electrical stimulation and corticosterone: a possible therapeutic target to Bell's palsy

<p>Abstract</p> <p>Background</p> <p>The etiology of Bell's palsy can vary but anterograde axonal degeneration may delay spontaneous functional recovery leading the necessity of therapeutic interventions. Corticotherapy and/or complementary rehabilitation interventions have been employed. Thus the natural history of the disease reports to a neurotrophic resistance of adult facial motoneurons leading a favorable evolution however the related molecular mechanisms that might be therapeutically addressed in the resistant cases are not known. Fibroblast growth factor-2 (FGF-2) pathway signaling is a potential candidate for therapeutic development because its role on wound repair and autocrine/paracrine trophic mechanisms in the lesioned nervous system.</p> <p>Methods</p> <p>Adult rats received unilateral facial nerve crush, transection with amputation of nerve branches, or sham operation. Other group of unlesioned rats received a daily functional electrical stimulation in the levator labii superioris muscle (1 mA, 30 Hz, square wave) or systemic corticosterone (10 mgkg^-1). Animals were sacrificed seven days later.</p> <p>Results</p> <p>Crush and transection lesions promoted no changes in the number of neurons but increased the neurofilament in the neuronal neuropil of axotomized facial nuclei. Axotomy also elevated the number of GFAP astrocytes (143% after crush; 277% after transection) and nuclear FGF-2 (57% after transection) in astrocytes (confirmed by two-color immunoperoxidase) in the ipsilateral facial nucleus. Image analysis reveled that a seven days functional electrical stimulation or corticosterone led to elevations of FGF-2 in the cytoplasm of neurons and in the nucleus of reactive astrocytes, respectively, without astrocytic reaction.</p> <p>Conclusion</p> <p>FGF-2 may exert paracrine/autocrine trophic actions in the facial nucleus and may be relevant as a therapeutic target to Bell's palsy.</p

Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis

Introduction: The PI3K/AKT pathway is activated in 43-70% of breast cancer (BC)-patients and promotes the metastatic potential of BC cells by increasing cell proliferation, invasion and radioresistance. Therefore, AKT1-inhibition in combination with radiotherapy might be an effective treatment option for triple-negative breast cancer (TNBC)-patients with brain metastases. Methods: The impact of AKT1-knockout (AKT1_KO) and AKT-inhibition using Ipatasertib on MDA-MB-231 BR cells was assessed using in vitro cell proliferation and migration assays. AKT1-knockout in MDA-MB-231BR cells was performed using CRISPR/Cas9. The effect of AKT1-knockout on radiosensitivity of MDA-MB-231BR cell lines was determined via colony formation assays after cell irradiation. To detect genomic variants in AKT1_KO MDA-MB-231BR cells, whole-genome sequencing (WGS) was performed. Results: Pharmacological inhibition of AKT with the pan-AKT inhibitor Ipatasertib led to a significant reduction of cell viability but did not impact cell migration. Moreover, only MDA-MB-231BR cells were sensitized following Ipatasertib-treatment. Furthermore, specific AKT1-knockout in MDA-MB-231BR showed reduced cell viability in comparison to control cells, with significant effect in one of two analyzed clones. Unexpectedly, AKT1 knockout led to increased cell migration and clonogenic potential in both AKT1_KO clones. RNAseq-analysis revealed the deregulation of CTSO, CYBB, GPR68, CEBPA, ID1, ID4, METTL15, PBX1 and PTGFRN leading to the increased cell migration, higher clonogenic survival and decreased radiosensitivity as a consequence of the AKT1 knockout in MDA-MB-231BR. Discussion; Collectively, our results demonstrate that Ipatasertib leads to radiosensitization and reduced cell proliferation of MDA-MB-231BR. AKT1-inhibition showed altered gene expression profile leading to modified cell migration, clonogenic survival and radioresistance in MDA-MB-231BR. We conclude, that AKT1-inhibition in combination with radiotherapy contribute to novel treatment strategies for breast cancer brain metastases

As atitudes dos alunos para com a Matemática: Um estudo em duas turmas do 6.º ano do Ensino Básico

O presente artigo irá incidir sobre um estudo realizado ao longo do ano letivo de 2017/2018, no âmbito da “Prática de Ensino Supervisionada II” do Mestrado em Ensino do 1.º Ciclo do Ensino Básico e de Matemática e Ciências Naturais no 2.º Ciclo do Ensino Básico. Este estudo teve como objetivo conhecer as atitudes dos alunos de uma turma do 6.º ano do ensino básico para com a Matemática antes e após o período de intervenção, de modo a compará-las e a compreender que aspetos da prática interventiva podem ter influenciado eventuais mudanças de atitude. Para tal, optou-se por uma metodologia quantitativa e, como método de recolha de dados, foram aplicados questionários, com itens fechados e abertos, antes e após o período de intervenção, assim como foram realizadas entrevistas aos alunos que mais diferenças mostraram entre estes dois períodos. Embora não se tenha verificado uma diferença significativa nas atitudes dos alunos para com a disciplina, em termos gerais o grupo evoluiu no que diz respeito a este domínio. Os resultados, para além de mostrarem que os alunos se sentem mais apoiados quando estão mais professoras presentes na sala de aula, também evidenciam que o tipo de atividades que foram desenvolvidas durante o período de intervenção – atividades exploratórias com recurso a materiais manipuláveis – constitui uma motivação extra para que os discentes se envolvam no trabalho matemático em sala de aula.Abstract This article will focus on a study carried out during 2017/2018 academic year, within the scope of the “Supervised Teaching Practice II” of the Master in Teaching in the 1st Cycle of Basic Education and Maths and Science in the 2nd Cycle of Basic Education. This study aimed to know the attitudes of students in a 6th grade class of basic education towards mathematics before and after the intervention period, in order to compare them and to understand which aspects of the interventional practice may have influenced possible changes in attitudes. To this end, a quantitative methodology was chosen and, as a method of data collection, questionnaires were applied, with closed and open items, before and after the intervention period, as well as interviews with students that most showed differences between these two periods. Although there was no significant difference in the students' attitudes towards the discipline, in general terms the group has evolved with respect to this domain. The results, in addition to showing that students feel more supported when there are more teachers present in the classroom, also show that the type of activities that were developed during the intervention period - exploratory activities using manipulable materials - constitutes extra motivation for students to get involved in mathematical work in the classroom.Résumé Cet article se concentrera sur une étude réalisée au cours de l'année académique 2017/2018, dans le cadre de la «Pratique pédagogique supervisée II» du Master en enseignement du 1er cycle de l'enseignement de base et des mathématiques et sciences naturelles du 2e Cycle d'éducation de base. Cette étude visait à connaître les attitudes des élèves d'une classe de base de 6e année à l'égard des mathématiques avant et après la période d'intervention, afin de les comparer et de comprendre quels aspects de la pratique interventionnelle ont pu influencer possibles changements d'attitude. À cette fin, une méthodologie quantitative a été choisie et, comme méthode de collecte des données, des questionnaires ont été appliqués, avec des éléments fermés et ouverts, avant et après la période d'intervention, ainsi que des entretiens avec des étudiants qui ont le plus montré des différences entre cettes deux périodes. Bien qu'il n'y ait pas de différence significative dans les attitudes des étudiants vis-à vis de la discipline, en général le groupe a évolué par rapport à ce domaine. Les résultats, en plus de montrer que les élèves se sentent plus soutenus lorsqu'ils sont plus d'enseignants présents dans la salle de classe, montrent également que le type d'activités développées au cours de la période d'intervention - activités exploratoires utilisant du matériel manipulable - constitue également motivation supplémentaire pour les élèves à s'impliquer dans des travaux mathématiques en classe.info:eu-repo/semantics/publishedVersio

Perceptions of Tenure and Tenure Reform in Academic Pharmacy

Objectives. To determine the academic pharmacy community’s perceptions of and recommendations for tenure and tenure reform

Comparison Between Spectral-Domain and Swept-Source Optical Coherence Tomography Angiographic Imaging of Choroidal Neovascularization

PURPOSE. The purpose of this study was to compare imaging of choroidal neovascularization (CNV) using swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA). METHODS. Optical coherence tomography angiography was performed using a 100-kHz SS-OCT instrument and a 68-kHz SD-OCTA instrument (Carl Zeiss Meditec, Inc.). Both 3 x 3-and 6 x 6-mm(2) scans were obtained on both instruments. The 3 x 3-mm(2) SS-OCTA scans consisted of 300 A-scans per B-scan at 300 B-scan positions, and the SD-OCTA scans consisted of 245 A-scans at 245 B-scan positions. The 6 x 6-mm(2) SS-OCTA scans consisted of 420 A-scans per B-scan at 420 B-scan positions, and the SD-OCTA scans consisted of 350 A-scans and 350 B-scan positions. B-scans were repeated four times at each position in the 3 x 3-mm(2) scans and twice in the 6 x 6-mm(2) scans. Choroidal neovascularization was excluded if not fully contained within the 3 x 3-mm(2) scans. The same algorithm was used to detect CNV on both instruments. Two graders outlined the CNV, and the lesion areas were compared between instruments. RESULTS. Twenty-seven consecutive eyes from 23 patients were analyzed. For the 3 x 3-mm(2) scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.17 and 1.01 mm(2), respectively (P = 0.047). For the 6 x 6-mm(2) scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.24 and 0.74 mm(2) (P = 0.003). CONCLUSIONS. The areas of CNV tended to be larger when imaged with SS-OCTA than with SD-OCTA, and this difference was greater for the 6 x 6-mm(2) scans.Carl Zeiss Meditec, Inc.National Eye InstituteResearch to Prevent Blindness, Inc. (New York, NY)National Eye Institute Center Core GrantCAPES Foundation, Ministry of Education of Brazil (Brasilia, Brazil)German Research FoundationUniv Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilUniv Washington, Dept Bioengn, Seattle, WA 98195 USACarl Zeiss Meditec Inc, Adv Dev, Dublin, CA USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilNational Eye Institute: R01EY024158National Eye Institute Center Core Grant: P30EY014801German Research Foundation: SCHA 1869/1-1Web of Scienc

Automated Quantitation of Choroidal Neovascularization: A Comparison Study Between Spectral-Domain and Swept-Source OCT Angiograms

PURPOSE. To compare the lesion sizes of choroidal neovascularization (CNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) and measured using an automated detection algorithm. METHODS. Patients diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 x 3-mm and 6 x 6-mm scans. The complex optical microangiography (OMAG(C)) algorithm was used to generate the OCTA images. Optical coherence tomography A datasets for imaging CNV were derived by segmenting from the outer retina to 8 mu m below Bruch's membrane. An artifact removal algorithm was used to generate angiograms free of retinal vessel projection artifacts. An automated detection algorithm was developed to quantify the size of the CNV. Automated measurements were compared with manual measurements. Measurements from SD-OCTA and SS-OCTA instruments were compared as well. RESULTS. Twenty-seven eyes from 23 subjects diagnosed with CNV were analyzed. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 x 3-mm (P = 0.61, paired t-test) and 6 x 6-mm (P = 0.09, paired t-test) scans and the SS-OCTA 3 x 3-mm (P = 0.41, paired t-test) and 6 x 6-mm (P = 0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 3 3-mm scans (P = 0.011, paired sample t-test) and the 6 x 6-mm scans (P = 0.021, paired t-test). CONCLUSIONS. The automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements.Carl Zeiss Meditec, Inc. (Dublin, CA)National Eye InstituteResearch to Prevent Blindness, Inc., New York, New YorkNational Eye Institute Center Core GrantCAPES Foundation, Ministry of Education of Brazil, Brasilia-BrazilGerman Research Foundation (DFG)Research to Prevent BlindnessUniv Washington, Dept Bioengn, 3720 NE 15th Ave, Seattle, WA 98195 USAUniv Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilCarl Zeiss Meditec Inc, Adv Dev, Dublin, CA USAUniv Washington, Dept Ophthalmol, 3720 NE 15th Ave, Seattle, WA 98195 USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilNational Eye Institute: R01EY024158National Eye Institute Center Core Grant: P30EY014801German Research Foundation (DFG): SCHA 1869/1-1Web of Scienc

Anterior anal sphincter repair can be of long term benefit: a 12-year case cohort from a single surgeon

BACKGROUND: Early surgical results of anterior sphincter repair for faecal incontinence can be good, but in the longer term are often disappointing. This study aimed to determine the short and long term outcomes from anterior sphincter repair and identify factors predictive of long term success. METHODS: Patients who underwent anterior sphincter repair between 1989 and 2001 in one institution were identified. Postal questionnaires were sent to patients, which included validated scoring systems for symptom severity and quality of life assessments for faecal incontinence. Patient demographics and risk factors were recorded as were the results of anorectal physiology studies and endoanal ultrasound. RESULTS: Eighty-five patients underwent repair by one consultant. The length of follow up ranged from 1 to 12 years. Most patients (96%) had early symptom improvement postoperatively. Of the 47 patients assessed long term (≥ 5 years), 28 (60%) maintained this success. Significant improvements in quality of life were observed (P < 0.001). Neither patient, surgical nor anorectal physiology study parameters were predictive of outcome. CONCLUSION: There were no predictive factors of outcome success and no changes in anal manometry identified, however anterior sphincter repair remains worthwhile. Changes in compliance of the anorectum may be responsible for symptom improvement

Cross-cultural conceptualization of a good end of life with dementia:A qualitative study

Background: Research on the nature of a “good death” has mostly focused on dying with cancer and other life-limiting diseases, but less so on dementia. Conceptualizing common cross-cultural themes regarding a good end of life in dementia will enable developing international care models. Methods: We combined published qualitative studies about end of life with dementia, focus group and individual interviews with the researchers, and video-conferencing and continuous email discussions. The interviews were audio-recorded and transcribed verbatim. The data were analyzed thematically, and the researchers developed common themes referring to their original studies. Results: Fourteen qualitative researchers representing 14 cross-cultural studies covering qualitative data of 121 people with dementia and 292 family caregivers. The researchers and data were from eight countries UK, The Netherlands, Japan, Portugal, Germany, Canada, Brazil, and Ireland. Three focus groups, five individual interviews, and video-conferencing were conducted and feedback on multiple iterations was gained by 190 emails between May 2019 and April 2020 until consensus was achieved. Nine cross-culturally common themes emerged from the discussions and shared interpretation of the data of persons with dementia and family caregivers. Three represent basic needs: “Pain and Symptoms Controlled,” “Being Provided Basic Care,” and “A Place like Home.” Other themes were “Having Preferences Met,” “Receiving Respect as a Person,” “Care for Caregivers,” “Identity Being Preserved,” “Being Connected,” and “Satisfaction with Life and Spiritual Well-being.” “Care for Caregivers” showed the greatest difference in emphasis across cultures. Good relationships were essential in all themes. Conclusions: The common cross-cultural themes comprise a framework underpinned by value placed on personhood and dignity, emphasizing that interdependency through relationships is essential to promote a good end of life with dementia. These themes and valuing the importance of relationships as central to connecting the themes could support care planning and further development of a dementia palliative care model.info:eu-repo/semantics/publishedVersio