Mapping of oxidative stress responses of human tumor cells following photodynamic therapy using hexaminolevulinate

<p>Abstract</p> <p>Background</p> <p>Photodynamic therapy (PDT) involves systemic or topical administration of a lesion-localizing photosensitizer or its precursor, followed by irradiation of visible light to cause singlet oxygen-induced damage to the affected tissue. A number of mechanisms seem to be involved in the protective responses to PDT, including activation of transcription factors, heat shock proteins, antioxidant enzymes and apoptotic pathways.</p> <p>Results</p> <p>In this study, we address the effects of a destructive/lethal hexaminolevulinate (HAL) mediated PDT dose on the transcriptome by using transcriptional exon evidence oligo microarrays. Here, we confirm deviations in the steady state expression levels of previously identified early defence response genes and extend this to include unreported PDT inducible gene groups, most notably the metallothioneins and histones. HAL-PDT mediated stress also altered expression of genes encoded by mitochondrial DNA (mtDNA). Further, we report PDT stress induced alternative splicing. Specifically, the ATF3 alternative isoform (deltaZip2) was up-regulated, while the full-length variant was not changed by the treatment. Results were independently verified by two different technological microarray platforms. Good microarray, RT-PCR and Western immunoblotting correlation for selected genes support these findings.</p> <p>Conclusion</p> <p>Here, we report new insights into how destructive/lethal PDT alters the transcriptome not only at the transcriptional level but also at post-transcriptional level via alternative splicing.</p

Lutte étagée ciblée et pulvérisation à très bas volume. Une protection insecticide du cotonnier moins onéreuse et plus respectueuse de l'environnement

La lutte étagée ciblée consiste à évaluer le niveau des populations de ravageurs la veille du traitement. Les insectes observés sont les chenilles des capsules ou des feuilles, les acariens, les aleurodes et les pucerons. Les niveaux de population sont confrontés à des seuils d'intervention et les résultats obtenus guident les choix des doses et des types d'insecticides utilisés. En 1995, 1 519 postes d'observateurs saisonniers ont été créés, pour une rémunération globale de 56 millions de francs CFA. Prévulgariséesur 407 ha en 1990, la lutte étagée ciblée a été vulgarisée sur 85 000 ha en 1995. Cette innovation nécessite la mise en oeuvre d'importants moyens dans le domaine de la formation et du suivi. La pulvérisation à très bas volume (TBV) épand 10 litres de bouillie aqueuse par hectare. Les insecticides utilisés sont des concentrés émulsionnables, moins chers que les insecticides pour ultra bas volume. A dose de matière active égale, un traitement TBV est 20 % moins cher qu'un traitement ULV. Les anciens appareils de traitement ultra bas volume ont été adaptés pour la pulvérisation TBV par un changement de buse et l'adjonction d'un réservoir auxiliaire. L'utilisation de la pulvérisation TBV a réduit les risques d'intoxication des opérateurs par inhalation (nuage de pulvérisation moins volatile) et par contact (bouillies insecticides aqueuses et moins concentrées). En permettant des économies de matières actives atteignant 30 à 40 %, la lutte étagée ciblée a permis de limiter les effets néfastes potentiels de la protection insecticide sur l'environnement. En 1992, la protection insecticide coûtait 9 005 francs CFA à l'hectare. En 1995, malgré la dévaluation, elle a coûté 10 700 francs CFA à l'hectare. En francs CFA constants, le coût de la protection insecticide a chuté de 41 % entre 1992 et 1995. Pour la campagne agricole 1995, l'économie réalisée a dépassé 900 millions de francs CFA

Comorbidities treated in primary care in children with chronic fatigue syndrome

Background: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a complex condition. Causal factors are not established, although underlying psychological or immunological susceptibility has been proposed. We studied primary care diagnoses for children with CFS/ME, with children with another hospital diagnosis (type 1 diabetes mellitus [T1DM]) and the general child population as comparison groups. Methods: All Norwegian children born 1992–2012 constituted the study sample. Children with CFS/ME (n = 1670) or T1DM (n = 4937) were identified in the Norwegian Patient Register (NPR) (2008-2014). Children without either diagnosis constituted the general child population comparison group (n = 1337508). We obtained information on primary care diagnoses from the Norwegian Directorate of Health. For each primary care diagnosis, the proportion and 99 % confidence interval (CI) within the three groups was calculated, adjusted for sex and age by direct standardization. Results: Children with CFS/ME were more often registered with a primary care diagnosis of weakness/general tiredness (89.9 % [99 % CI 88.0 to 91.8 %]) than children in either comparison group (T1DM: 14.5 % [99 % CI: 13.1 to 16.0 %], general child population: 11.1 % [99 % CI: 11.0 to 11.2 %]). Also, depressive disorder and anxiety disorder were more common in the CFS/ME group, as were migraine, muscle pain, and infections. In the 2 year period prior to the diagnoses, infectious mononucleosis was registered for 11.1 % (99 % CI 9.1 to 13.1 %) of children with CFS/ ME and for 0.5 % (99 % CI (0.2 to 0.8 %) of children with T1DM. Of children with CFS/ME, 74.6 % (1292/1670) were registered with a prior primary care diagnosis of weakness / general tiredness. The time span from the first primary care diagnosis of weakness / general tiredness to the specialist health care diagnosis of CFS/ME was 1 year or longer for 47.8 %. Conclusions: This large nationwide registry linkage study confirms that the clinical picture in CFS/ME is complex. Children with CFS/ME were frequently diagnosed with infections, supporting the hypothesis that infections may be involved in the causal pathway. The long time span often observed from the first diagnosis of weakness / general tiredness to the diagnosis of CFS/ME might indicate that the treatment of these patients is sometimes not optimal.publishedVersio

Genome wide single cell analysis of chemotherapy resistant metastatic cells in a case of gastroesophageal adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Metastatic progression due to development or enrichment of therapy-resistant tumor cells is eventually lethal. Molecular characterization of such chemotherapy resistant tumor cell clones may identify markers responsible for malignant progression and potential targets for new treatment. Here, in a case of stage IV adenocarcinoma of the gastroesophageal junction, we report the successful genome wide analysis using array comparative genomic hybridization (CGH) of DNA from only fourteen tumor cells using a bead-based single cell selection method from a bone metastasis progressing during chemotherapy.</p> <p>Case presentation</p> <p>In a case of metastatic adenocarcinoma of the gastroesophageal junction, the progression of bone metastasis was observed during a chemotherapy regimen of epirubicin, oxaliplatin and capecitabine, whereas lung-, liver and lymph node metastases as well as the primary tumor were regressing. A bone marrow aspirate sampled at the site of progressing metastasis in the right iliac bone was performed, and single cell molecular analysis using array-CGH of Epithelial Specific Antigen (ESA)-positive metastatic cells, and revealed two distinct regions of amplification, 12p12.1 and 17q12-q21.2 amplicons, containing the KRAS (12p) and ERBB2 (HER2/NEU) (17q) oncogenes. Further intrapatient tumor heterogeneity of these highlighted gene copy number changes was analyzed by fluorescence in situ hybridization (FISH) in all available primary and metastatic tumor biopsies, and ErbB2 protein expression was investigated by immunohistochemistry.</p> <p>ERBB2 was heterogeneously amplified by FISH analysis in the primary tumor, as well as liver and bone metastasis, but homogenously amplified in biopsy specimens from a progressing bone metastasis after three initial cycles of chemotherapy, indicating a possible enrichment of erbB2 positive tumor cells in the progressing bone marrow metastasis during chemotherapy. A similar amplification profile was detected for wild-type KRAS, although more heterogeneously expressed in the bone metastasis progressing on chemotherapy. Correspondingly, the erbB2 protein was found heterogeneously expressed by immunohistochemical staining of the primary tumor of the gastroesophageal junction, while negative in liver and bone metastases, but after three initial cycles of palliative chemotherapy with epirubicin, oxaliplatin and capecetabine, the representative bone metastasis stained strongly positive for erbB2.</p> <p>Conclusion</p> <p>Global analysis of genetic aberrations, as illustrated by performing array-CGH analysis on genomic DNA from only a few selected tumor cells of interest sampled from a progressing bone metastasis, can identify relevant therapeutic targets and genetic aberrations involved in malignant progression, thus emphasizing the importance and feasibility of this powerful tool on the road to more personalized cancer therapies in the future.</p

Muligheter og utfordringer: En intervjustudie av hvordan fosterhjemskonsulenter opplever sitt handlingsrom til å involvere barn av fosterforeldre

Forskningen på barn av fosterforeldre er beskjeden, og studiene som foreligger belyser i hovedsak hvordan fosterforeldre og deres barn opplever fosterhjemsoppdraget og samarbeidet med barnevernet. Denne masteroppgaven undersøker hvordan barnevernet involverer fosterforeldrenes egne barn i fosterhjemsarbeidet. Problemstillingen er som følger: Hvordan opplever fosterhjemskonsulenter sitt handlingsrom til å involvere barn av fosterforeldre? Oppgavens empiriske grunnlag er syv semi-strukturerte intervju og ett fokusgruppeintervju med totalt 14 fosterhjemskonsulenter. Analysene baserer seg på teorier om barns deltakelse og barneperspektivet. Deltakelse forstås her i bred betydning, både slik det er definert i lovverket og innenfor sosiokulturell teori. I tillegg til teori om deltakelse, har jeg inkludert begrepet «grensearbeid» og elementer fra Lipsky sin teori om bakkebyråkratene. Studien viser at i matchingsprosessen har fosterhjemskonsulentene et utenfra perspektiv på barn av fosterforeldre. Alderssammensetningen mellom barna begrunnes ut fra stabilitet, men også ut fra hva som er til det beste for barn av fosterforeldre. Vurderingene er basert på tidligere erfaringer, og ikke samtaler med de konkrete barna. De fleste informantene snakket med barn av fosterforeldre i forberedelsesfasen, både for å forberede og avklare at barna var positiv til å bli fosterfamilie. Flere beskriver imidlertid utfordringer med å forbedre barna tilstrekkelig på det som skal skje. Analysene viser at involveringen av barn av fosterforeldre blir mer tilfeldig og variert etter at fosterbarnet har flyttet inn. På oppfølgingsbesøk er det først og fremst fosterbarnet og fosterforeldrene barnevernet snakker med. Planlagte samtaler med barn av fosterforeldre ser først ut til å bli en prioritet i det fosterforeldre ber om det fordi ting har blitt «vanskelig». Denne praksisen begrunnes ut fra tre forhold; hensynet til barnets familieliv, antakelsen om at fosterforeldre er kompetente nok til å ivareta egne barn, samt mangel på tid og ressurser. Samtidig er det noen eksempler i studien på at ikke alle opplever tid og ressurser som en barriere for å involvere barna. Felles for disse informantene er at de har vært på kurs eller hatt praksiserfaringer som har endret deres måte å tenke om barn av fosterforeldre sin rolle i fosterhjemsarbeidet. Det kan synes som at disse informantene har erfart at det ikke nødvendigvis trenger å være ressurskrevende å gi barn av fosterforeldre oppmerksomhet, og derigjennom bidra til at de blir sett og inkludert

Barnevern i krisetid. Barneverntjenestens arbeid med vold og overgrep under koronapandemiens første fase

Notatet undersøker hvordan barneverntjenesten ivaretok arbeidet med vold og overgrep under den første fasen av koronapandemien, fra den såkalte «nedstengningen» av samfunnet 12. mars og frem mot gradvis normalisering sommeren 2020. Vi beskriver hvordan korona påvirket organisering, saksarbeid og tverrfaglig samarbeid, og vi kommer med forslag til hvordan tjenesten kan lære av disse erfaringene. Studien er basert på intervjuer med ledere ved 20 barneverntjenester. Den er finansiert av Bufdir

Youth and acne - a survey among 14- and 15-year-olds

Acne is a condition which can give both physical and psychological scars. Young persons are vulnerable to the negative effects of acne. Our survey investigates whether the knowledge about causes and treatment of acne is satisfactory among 14- and 15-year-olds. How does acne effect their self-esteem and well-being in school? Is there a need for information and how is their help-seeking behaviour? Our survey included 304 students from 5 different schools. The response rate was 99%. The results show that 57,6% found acne a troublesome condition, 27,1% reported a negative impact on their self-esteem and 11,5% reduced well-being in school. The knowledge of causes was scored on a scale from 0-10. The average was 5,43, which defines a need for distribution of information. 63,8% still think that chocolate is a cause of acne. Among options of treatment Clearasil is best known, despite being less effective than other products not on prescription. It is worrysome that 62,8 % think bad hygiene is a cause of acne, highlighting the harmful prejudice that acne is a filthy disease. 59,7% reported washing their face more frequently to avoid acne. Our survey confirms that most young people are affected by acne, but very few contact a doctor (3,9%). There is a need for information about causes and effective treatment to help battle the stigma of a condition which is easy to treat. It is important to lower the threshold for seeking medical help

Evaluering av Los-ordningen for ungdom

Denne rapporten er en evaluering av Barne-, ungdoms- og familiedirektoratets tilskuddsordning «Støtte til oppfølgings- og losfunksjoner for ungdom». Målsettingen har vært å undersøke i hvilken grad og hvordan losfunksjonen bidrar i kommuner og bydelers arbeid med å få til tett oppfølging av ungdom som står i fare for å falle ut av ordinær skolegang, og til bedre samordning av kommunale tjenester rettet mot målgruppen. Evalueringen bygger på intervjuer med loser, deres ledere, samarbeidspartnere og ungdom, og spørreundersøkelse til loser og deres ledere i kommuner og bydeler