Die Rolle von Kontextfaktoren für das Stillen und ihre potentielle Integration in Leitlinien am Beispiel Deutschland, Großbritannien und Ghana

Introduction: Breastfeeding is recognized as an important public health issue with high social and economic implications. According to the WHO, it should be initiated within one hour after birth, exclusive breastfeeding should be practiced for six months, and the entire period should last for two years. However, breastfeeding rates are sub-optimal at a worldwide scale and could be improved. Recommendations are commonly translated into guidelines to be applied in health service delivery. In order to increase the effectiveness of guidelines, these should be adapted to their social and cultural context. The aim of this dissertation therefore was to evaluate whether relevant contextual factors, such as social determinants that affect breastfeeding are addressed in respective guidelines. In order to contrast results, three countries – Germany, the United Kingdom and Ghana – were compared. Methods: The research was carried out in two steps. First, a Realist Review was conducted. This methodological approach is borrowed from Systematic Reviews, but employs a broader search. It aims at verifying which contextual factors take effect on a certain health outcome in what type of context. For this research, context was defined as the social contexts where breastfeeding takes place, with contextual factors defined as social determinants, and the respective outcomes as breastfeeding periods as recommended by the WHO. Retrieved studies were first subject to an overall quality assessment according to criteria from SIGN. They were then were analyzed by Pawson´s Realist Synthesis method. For the second step, two guidelines per country were selected. The first referred to the postnatal period itself, and the second to a health risk related to breastfeeding. Guidelines were then appraised for their quality with the AGREE II tool. Thereafter, they were scrutinized with the BIAS FREE Framework, an instrument for detecting social biases. Results: The search and screening process from the Realist Review resulted in eight studies for Germany, 11 for the United Kingdom and six for Ghana. Findings from the Realist Synthesis revealed that there were clear relationships between social determinants and breastfeeding. For all three countries, young maternal age, a low maternal educational level/SES, as well as social networks proved relevant for all breastfeeding periods. Culture manifested itself differently in the three regions, and was of major importance in the United Kingdom. Work regulation and parental leave in combination with economic constraints were a major challenge to start and continue breastfeeding in the United Kingdom, and led to the interruption of exclusive breastfeeding in Ghana, which is highly problematic in times of HIV. Regarding the guideline analyses, social determinants that were found to be relevant are not taken into account as such. For example, women are addressed as “the mother”, ignoring their socio-demographic characteristics, and also neglecting their social reality, e.g. the influence of family members/peers on the infant feeding decision. One-parent families are underrepresented, and quality assurance limited to medical factors only. Recommendations: The methodological approach of the Realist Review proved suitable for the aim of this research and is therefore highly recommended. The fact that social determinants are not part of breastfeeding-related guidelines indicates a dearth in guideline development and implies a reduced effectiveness. In order to scale up breastfeeding rates, it is therefore recommended to address them accordingly to enhance effectiveness and thus to achieve health equity in mothers and their children.Einleitung: Die Ernährung mit Muttermilch ist eine wichtiger Aspekt der öffentlichen Gesundheit mit starken gesellschaftlichen und ökonomischen Auswirkungen. Die WHO empfiehlt möglichst frühzeitiges Anlegen nach der Geburt, eine Stilldauer des ausschließlichen Stillens von sechs Monaten und eine gesamte Stillperiode von zwei Jahren. Diese Vorgaben werden jedoch weltweit nicht erreicht und Stillraten könnten in allen Ländern optimiert werden. Die Empfehlungen wie die zum Stillen werden in der Regel in Leitlinien umgesetzt. Um die Effektivität dieser Leitlinien zu erhöhen, sollten diese an den jeweiligen sozialen und kulturellen Kontext angepasst werden. Das Ziel dieser Dissertation war es daher herauszufinden, ob relevante kontextuelle Faktoren Bestandteil der entsprechenden Leitlinien sind. Um Ergebnisse besser zu kontrastieren, wurden die drei Länder – Deutschland, Großbritannien und Ghana – verglichen. Methodik: Die Forschungsarbeit wurde in zwei Schritten umgesetzt. Zunächst wurde ein Realist Review durchgeführt. Diese Methodik entstammt dem Systematischen Review, wobei zum Einen eine breitere Suche vorgenommen wird und hat zum Anderen zum Ziel, kontextuelle Faktoren, die einen bestimmten Effekt auf einen gesundheitlichen Endpunkt haben, zu verifizieren. Für das Forschungsvorhaben wurde Kontext definiert als der soziale Kontext, in dem Stillen stattfindet, und als kontextuelle Faktoren soziale Determinanten, die das Stillen beeinflussen. Der Endpunkt waren die jeweiligen Stillperioden, wie sie von der WHO empfohlen werden. Die Studien, die aus dem Realist Review resultierten, wurden zunächst einer Bewertung ihrer Studiengüte/Studienqualität mit SIGN unterzogen und anschließend mit der Realist Synthesis-Methode nach Pawson analysiert. Im zweiten Schritt wurden zwei Leitlinien pro Land ausgesucht, wobei die erste Relevanz für die postnatale Periode, und die zweite für ein Gesundheitsproblem, das durch das Stillen beeinflusst wird, hatte. Die Qualität der Leitlinienerstellung wurde dann mit dem AGREE II-Instrument bewertet. Anschließend wurden sie mit dem BIAS-FREE Framework analysiert, um einen sozialen Bias zu identifizieren. Ergebnisse: Die Literatursuche und der Screening-Prozess resultierten in acht Studien für Deutschland, elf für Großbritannien und sechs für Ghana. Die Analyse mit dem Realist Synthesis belegte, dass einen klaren Zusammenhang zwischen einigen sozialen Determinanten und dem Stillen gibt. Für alle drei Länder waren junges Alter der Mutter, ein niedriger Bildungsgrad der Mutter bzw. SES, und soziale Netzwerke relevant für das Stillen. Kultur manifestierte sich unterschiedlich in den drei Regionen, und war insbesondere für Großbritannien von großer Bedeutung. Die Arbeitsplatzregelung zum Stillen und die Dauer des Mutterschutzes bzw. Elternzeit stellten sich als bedeutsames Hindernis in wirtschaftlich schwierigen Zeiten für das Stillen per se heraus, insbesondere für die Stilldauer in Großbritannien bzw. in Ghana führte es zu einem vorzeitigen Unterbrechen des ausschließlichen Stillens, was als problematisch erachtet werden muss in Zeiten von HIV. Die Analyse der Leitlinien ergab, dass relevante soziale Determinanten an sich nicht berücksichtigt wurden. Zum Beispiel wurden Frauen als “die Mutter“ adressiert ohne Bezugnahme auf ihre soziodemographischen Charakteristika oder ihre sozialen Realität, wie bspw. der Einfluss von Familie bzw. Peers auf die Stillentscheidung. Ein-Eltern-Familien waren unterrepräsentiert, und Maßnahmen zur Qualitätssicherung beziehen sich ausschließlich auf medizinische Inhalte. Empfehlungen: Die methodische Herangehensweise mit dem Realist Review erwies sich als außerordentlich geeignet, um das Forschungsziel zu erreichen und ist daher sehr empfehlenswert für vergleichbare Fragestellungen. Die Tatsache, dass soziale Determinanten nicht Bestandteil von Leitlinien zum Stillen sind, deutet auf eine Lücke in der Leitlinienerstellung hin und impliziert indirekt eine begrenzte Effektivität derselben. Um die Stillraten zu erhöhen und die gesundheitliche Gleichheit von Müttern und ihren Kindern zu verbessern, wird daher empfohlen, diese zu entsprechend einzuarbeiten

Data on the descriptive overview and the quality assessment details of 12 qualitative research papers

This data article presents the supplementary material for the review paper “Role of acceptability barriers in delayed diagnosis of Tuberculosis: Literature review from high burden countries” (Barnabishvili et al., in press) [1]. General overview of 12 qualitative papers, including the details about authors, years of publication, data source locations, study objectives, overview of methods, study population characteristics, as well as the details of intervention and the outcome parameters of the papers are summarized in the first two tables included to the article. Quality assessment process of the methodological strength of 12 papers and the results of the critical appraisal are further described and summarized in the second part of the article. Keywords: Acceptability of Health Care, Access to Health Care, Drug-resistant tuberculosis, High M/XDR-TB burden countries, Quality assessment of qualitative studies, Critical appraisal of qualitative studie

Deletion of Adipose Triglyceride Lipase Links Triacylglycerol Accumulation to a More-Aggressive Phenotype in A549 Lung Carcinoma Cells

Adipose triglyceride lipase (ATGL) catalyzes the rate limiting step in triacylglycerol breakdown in adipocytes but is expressed in most tissues. The enzyme was shown to be lost in many human tumors, and its loss may play a role in early stages of cancer development. Here, we report that loss of ATGL supports a more-aggressive cancer phenotype in a model system in which ATGL was deleted in A549 lung cancer cells by CRISPR/Cas9. We observed that loss of ATGL led to triacylglycerol accumulation in lipid droplets and higher levels of cellular phospholipid and bioactive lipid species (lyso- and ether-phospholipids). Label-free quantitative proteomics revealed elevated expression of the pro-oncogene SRC kinase in ATGL depleted cells, which was also found on mRNA level and confirmed on protein level by Western blot. Consistently, higher expression of phosphorylated (active) SRC (Y416 phospho-SRC) was observed in ATGL-KO cells. Cells depleted of ATGL migrated faster, which was dependent on SRC kinase activity. We propose that loss of ATGL may thus increase cancer aggressiveness by activation of pro-oncogenic signaling via SRC kinase and increased levels of bioactive lipids

Deletion of Adipose Triglyceride Lipase Links Triacylglycerol Accumulation to a More-Aggressive Phenotype in A549 Lung Carcinoma Cells

Adipose triglyceride lipase (ATGL) catalyzes the rate limiting step in triacylglycerol breakdown in adipocytes but is expressed in most tissues. The enzyme was shown to be lost in many human tumors, and its loss may play a role in early stages of cancer development. Here, we report that loss of ATGL supports a more-aggressive cancer phenotype in a model system in which ATGL was deleted in A549 lung cancer cells by CRISPR/Cas9. We observed that loss of ATGL led to triacylglycerol accumulation in lipid droplets and higher levels of cellular phospholipid and bioactive lipid species (lyso- and ether-phospholipids). Label-free quantitative proteomics revealed elevated expression of the pro-oncogene SRC kinase in ATGL depleted cells, which was also found on mRNA level and confirmed on protein level by Western blot. Consistently, higher expression of phosphorylated (active) SRC (Y416 phospho-SRC) was observed in ATGL-KO cells. Cells depleted of ATGL migrated faster, which was dependent on SRC kinase activity. We propose that loss of ATGL may thus increase cancer aggressiveness by activation of pro-oncogenic signaling via SRC kinase and increased levels of bioactive lipids

Deletion of Adipose Triglyceride Lipase Links Triacylglycerol Accumulation to a More-Aggressive Phenotype in A549 Lung Carcinoma Cells

Adipose triglyceride lipase (ATGL) catalyzes the rate limiting step in triacylglycerol breakdown in adipocytes but is expressed in most tissues. The enzyme was shown to be lost in many human tumors, and its loss may play a role in early stages of cancer development. Here, we report that loss of ATGL supports a more-aggressive cancer phenotype in a model system in which ATGL was deleted in A549 lung cancer cells by CRISPR/Cas9. We observed that loss of ATGL led to triacylglycerol accumulation in lipid droplets and higher levels of cellular phospholipid and bioactive lipid species (lyso- and ether-phospholipids). Label-free quantitative proteomics revealed elevated expression of the pro-oncogene SRC kinase in ATGL depleted cells, which was also found on mRNA level and confirmed on protein level by Western blot. Consistently, higher expression of phosphorylated (active) SRC (Y416 phospho-SRC) was observed in ATGL-KO cells. Cells depleted of ATGL migrated faster, which was dependent on SRC kinase activity. We propose that loss of ATGL may thus increase cancer aggressiveness by activation of pro-oncogenic signaling via SRC kinase and increased levels of bioactive lipids

Deletion of Adipose Triglyceride Lipase Links Triacylglycerol Accumulation to a More-Aggressive Phenotype in A549 Lung Carcinoma Cells

Adipose triglyceride lipase (ATGL) catalyzes the rate limiting step in triacylglycerol breakdown in adipocytes but is expressed in most tissues. The enzyme was shown to be lost in many human tumors, and its loss may play a role in early stages of cancer development. Here, we report that loss of ATGL supports a more-aggressive cancer phenotype in a model system in which ATGL was deleted in A549 lung cancer cells by CRISPR/Cas9. We observed that loss of ATGL led to triacylglycerol accumulation in lipid droplets and higher levels of cellular phospholipid and bioactive lipid species (lyso- and ether-phospholipids). Label-free quantitative proteomics revealed elevated expression of the pro-oncogene SRC kinase in ATGL depleted cells, which was also found on mRNA level and confirmed on protein level by Western blot. Consistently, higher expression of phosphorylated (active) SRC (Y416 phospho-SRC) was observed in ATGL-KO cells. Cells depleted of ATGL migrated faster, which was dependent on SRC kinase activity. We propose that loss of ATGL may thus increase cancer aggressiveness by activation of pro-oncogenic signaling via SRC kinase and increased levels of bioactive lipids

Targeted Chemotherapy of Glioblastoma Spheroids with an Iontronic Pump

Successful treatment of glioblastoma multiforme (GBM), the most lethal tumor of the brain, is presently hampered by (i) the limits of safe surgical resection and (ii) "shielding" of residual tumor cells from promising chemotherapeutic drugs such as Gemcitabine (Gem) by the blood brain barrier (BBB). Here, the vastly greater GBM cell-killing potency of Gem compared to the gold standard temozolomide is confirmed, moreover, it shows neuronal cells to be at least 10(4)-fold less sensitive to Gem than GBM cells. The study also demonstrates the potential of an electronically-driven organic ion pump ("GemIP") to achieve controlled, targeted Gem delivery to GBM cells. Thus, GemIP-mediated Gem delivery is confirmed to be temporally and electrically controllable with pmol min(-1) precision and electric addressing is linked to the efficient killing of GBM cell monolayers. Most strikingly, GemIP-mediated GEM delivery leads to the overt disintegration of targeted GBM tumor spheroids. Electrically-driven chemotherapy, here exemplified, has the potential to radically improve the efficacy of GBM adjuvant chemotherapy by enabling exquisitely-targeted and controllable delivery of drugs irrespective of whether these can cross the BBB.Funding Agencies|Ph.D. program Molecular Medicine (MOLMED) of the Medical University of Graz; Austrian Science Fund (FWF)Austrian Science Fund (FWF) [P28701, TAI 245]; FWF projectAustrian Science Fund (FWF) [P28701]; Medical University of Graz through the Ph.D. Program "Molecular Medicine"; DOC Fellowship of the Austrian Academy of Sciences at the Institute of Biophysics at the Gottfried Schatz Research Center, Medical University of Graz; Knut and Alice Wallenberg FoundationKnut &amp; Alice Wallenberg Foundation; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research; Austrian Science Fund (FWF) Doctoral school "DK Metabolic and Cardiovascular disease" [W1266]; SFB "Lipid hydrolysis" [F73]; Austrian ministry of Science, Research and Economy [Omics Center Graz project]</p