Abstract The aim of this study was to evaluate the treatment, course and outcome of pregnancy in Finland using two cohorts of diabetic women. The clinical cohort consisted of data from all 210 women with Type 1 diabetes and their 296 pregnancies managed between 1986 and 1995 in the two northernmost provinces of Finland. The register-based study population included all 1442 mothers with a singleton birth who had insulin treatment during pregnancy in 1991-1995 according to the Medical Birth Register. Of these mothers, 954 (66%) had pre-existing diabetes. Insulin-treated diabetes complicated 4.5/1000 births in Finland in 1991-1995, the prevalence of Type 1 diabetes being 2.9/1000 in the whole country and 3.3/1000 in Northern Finland. In the 1990's the care of these women shifted from tertiary level only to include the secondary level hospitals as well, and was more often carried out on an out-patient basis. This care policy in association with the self-monitoring of blood glucose levels contributed to an obvious improvement in glycaemic control during pregnancy. Despite that, the high proportion (73%) of women entering pregnancy with unsatisfactory glycaemic control did not decrease during the study period. Retinopathy complicated 134 (45.3%) diabetic pregnancies, while clinical nephropathy was found in 23 (7.8%) cases. Although retinopathy was more often aggravated during the first pregnancy, the occurrence of retinopathy or its severe form was not increased at the beginning of consecutive pregnancies. Of the mothers, 50 (16.9%) had pre-eclampsia during pregnancy, and in 28% of these cases it was classified as superimposed. It was found more often among primiparous than multiparous (25.6% vs. 11.0%, respectively), and its occurrence rose with the severity of diabetes. In both cohorts, the rates of preterm deliveries, Caesarean sections and large for gestational age (LGA) infants were significantly (p < 0.001) higher in Type 1 diabetic pregnancies than in the background population. The rates of congenital anomalies (CA) were 540-629/10000 in two study populations, both being 2-3-fold as compared to the background population. Cardiac malformations were most common, with anomalies in the genitourinary tract and the musculoskeletal organs being next in frequency. Sixty-three percent of malformed infants were boys. Though pregnancy itself was not found to worsen the prognosis of diabetes, at least in the short term, pregnancy in diabetic women still remains a high risk state with an increased rate of prematurity, operative deliveries, CAs and peri- and neonatal mortality. In order to decrease the mortality rate in diabetic births, attention should be directed at both the prevention of CA and at identifying the foetuses at risk for intrauterine death. The postneonatal mortality rate is also high, reflecting a shift in the deaths from the early neonatal period to a later age. Therefore, a combined mortality, including induced abortions, stillborns and infant deaths, would give a more realistic idea of the outcomes in diabetic pregnancies.

Thesis (MPH.) -- University of Limpopo, 2017. / Background: Ante natal care (ANC) service is a very important intervention to track the progress and to identify complications that might arise during pregnancy. The first ANC visit at a health facility is even more important as health providers are able to identify whether there are any risks to the mother and the unborn child and it should be initiated at the 1st trimester of pregnancy. Objectives: The study aim was to establish the knowledge and perceptions about ANC services among pregnant women in the Julesburg Local Area in the Mopani District of Limpopo Province. Methods: A quantitative cross-sectional research approach was used at six primary health care facilities in the Julesburg Local Area of the Mopani District in Limpopo Province. Stratified random sampling was used. Data were collected from 293 pregnant women using a self-administered questionnaire. . Data analysis was done using the International Business Management Statistical Package for Social Sciences 23 (SPSS 23). Results: The results reveal that a high percentage of pregnant women have adequate knowledge with regard to ANC services. The results further show that knowledge level of pregnant women has no association with educational level (P=0.488). With regard to perception, half of the respondents have positive perceptions of ANC services, while a further half have negative perceptions of these services. Conclusion: ANC service is of great importance to further reduce maternal and neonatal deaths as most of these deaths are avoidable. There is a need to strengthen the training programme of staff by providing further training exposure and health information to pregnant women with regard to the important of early ANC initiation and frequency of ANC visit need to be intensified. Keywords: Health care workers, antenatal care, knowledge, perception, initiation, utilization.

Background: Hypertension during pregnancy is a leading cause of birthing parent mortality and adverse pregnancy outcomes. Since non-metropolitan communities face higher rates of several risk factors for hypertension in pregnancy and shortages in obstetrical services, persons residing in non-metropolitan areas may be at increased risk for adverse outcomes compared to those living in metropolitan areas. Our study objectives were to examine by county of birthing parent residence (1) the prevalence of chronic hypertension (cHTN) and hypertensive disorders of pregnancy (HDP), and (2) the prevalence of adverse birthing parent and neonatal outcomes associated with hypertension. Methods: Using U.S. birth certificate data from 2016 to 2018, we described the prevalence of cHTN and HDP and the association of each with several birthing parent and neonatal outcomes, stratified by non-metropolitan versus metropolitan county of birthing parent residence. Multivariable Poisson regression models were used to calculate adjusted prevalence ratios for birthing parent and neonatal outcomes among individuals with cHTN or HDP who lived in non-metropolitan versus metropolitan U.S. counties. Results: The prevalence of cHTN and HDP for US live births was 2.2% and 7.4%, respectively, among non-metropolitan pregnant individuals and 1.8% and 6.6%, respectively, among metropolitan pregnant individuals. After adjusting for several sociodemographic characteristics among those with HDP, the prevalence ratio for an APGAR score < 7 at 5 minutes (aPR 1.34, 95% CI 1.29-1.38) and neonatal death (aPR 1.36, 95% CI 1.15-1.62) was increased among offspring born to women who resided in non-metropolitan counties. Similar results were seen among those with cHTN. Conclusion: The prevalence of cHTN and HDP is modestly more prevalent in non-metropolitan areas, but most pregnancy outcomes were similar among those residing in non-metropolitan areas compared to metropolitan areas. Further research should investigate the robustness of these findings using alternate definitions of rural and urban areas and the possible link between low APGAR score, low NICU admission, and neonatal death in non-metropolitan counties.

Background: Community engagement—the collaborative process of addressing issues that impact the well-being of a community—is a strategic effort to address community issues. The Gulf States Health Policy Center (GS-HPC) formed the Hattiesburg Area Health Coalition (HAHC) in November 2014 for the purpose of addressing policies impacting the health of Forrest and Lamar counties in Mississippi. Objectives: To chronicle the community-based participatory research (CBPR) process used by HAHC’s identification of infant and maternal health as a policy area, domestic violence in pregnancy as a priority area within infant and maternal health, and a community action plan (CAP) regarding this priority area. Methods: HAHC reviewed data and identified infant and maternal health as a priority area. They then conducted a policy scan of local prenatal health care to determine the policy area of domestic violence in pregnancy. Results: HAHC developed a CAP identifying three goals with regard to domestic violence and pregnancy that together informed policy. Changes included the development of materials specific to resources available in the area. The materials and recommended changes will first be implemented by Southeast Mississippi Rural Health Initiative (SeMRHI) through a screening question for all pregnant patients, and the adoption of policies for providing information and referrals. Conclusions: The lack of community-level data was a challenge to HAHC in identifying focus and priority areas, but this was overcome by shared leadership and community engagement. After completion of the CAP, 100% of expecting mothers receiving prenatal care in the area will be screened for domestic violence.

Preeclampsia (PE) is a disorder affecting 2-10% of pregnancies worldwide. Clinical signs include high blood pressure (HBP) and proteinuria in the mother after the 20th week of pregnancy. Currently, the only cure for PE is delivery of the fetus, which is often necessary preterm and thus dangerous for both mother and fetus. Maternal symptoms of PE are caused by excess anti-angiogenic proteins of placental origin called soluble Flt1s (sFlt1s). sFlt1 mRNA isoforms are produced by alternative polyadenylation (APA) of full-length Flt1 (fl-Flt1) pre- mRNA. While fl-Flt1 encodes a transmembrane protein, sFlt1s encode truncated proteins that are soluble. Multiple sFlt1 isoforms exist, and their respective contribution to the pathophysiology of PE is unclear. Furthermore, it is unknown whether there is a genome-wide role for APA in PE. In my thesis research, I developed a polyadenylation site sequencing method, and used this method to simultaneously quantify transcriptome-wide polyadenylation site usage and gene expression levels in normal, early-onset PE, and late-onset PE human placentae. I observed distinct expression profiles amongst the three groups, with differential expression of genes in several functional categories, including angiogenesis. I found that three sFlt1 isoforms account for >94% of all placental FLT1 transcripts, and that increased transcription of the entire FLT1 locus drives upregulation of both fl-Flt1 and sFlt1 in PE. I found that APA does not contribute substantially to PE pathophysiology. I also identified siRNAs that knock down sFlt1 mRNA efficiently in cell lines that pave the way for further development of novel RNAi based therapeutics to alleviate PE.

BACKGROUND: Pregnancy-induced hypertension (PIH) and gestational diabetes mellitus (GDM) are among the leading causes of disability and death for women and their babies. Identifying risk factors for these pregnancy-related complications is essential to their prevention. Studies identifying preventive models for PIH and GDM are few. OBJECTIVES: This study was designed to evaluate lifestyle and personal predictors of PIH and GDM in a cohort of nearly 20,000 pregnant women. METHODS: The exposure data for the study were derived from a combination of a telephone interview and a questionnaire completed approximately 2 months after conception during the period from 1984 to 1987. The initial questionnaires asked for information on three periods: 3 months before conception, at conception, and 2 months after conception. Subjects included 19,312 women, aged 18-<45 years, who did not have excessive intakes of alcohol or food, were neither underweight (BMI >18.5) nor extremely overweight (BMI <40), and did not use illegal drugs during the first trimester of pregnancy. Outcome data on the mother and baby were collected approximately one year after the expected data of delivery. Logistic regression models were used to estimate the odds ratios (OR), and 95% confidence intervals (CI), as well as receiver operating characteristic (ROC) curves predicting PIH and GDM. Akaike Information Criteria (AIC) were used to select the best predictors of these two outcomes. Factors found not to affect PIH or GDM (based on a two-unit decrease in the AIC) were excluded from the final models. RESULTS: Based on the outcome data collected, there were 204 PIH cases, 358 GDM cases, and 538 who had PIH and/or GDM. After selecting the outcome predictors using AIC values, we identified three predictive models—one each for PIH, GDM, and either PIH or GDM. Factors found to predict PIH included age, previous hypertension or type 1 or 2 diabetes, pre-pregnancy BMI, parity, exercise, red meat consumption, margarine consumption, cigarette smoking, and weight change at 2 months. The final AIC value for PIH was 2084.12 and the AUC value was 0.76. GDM was predicted by age, previous GDM (in an earlier pregnancy), pre-pregnant BMI, height, exercise, race, dairy consumption, and cigarette smoking, with an AIC value of 3288.74 and an AUC value of 0.70. The combined model (predicting either PIH or GDM) was best predicted by age, history of GDM in a previous pregnancy, pre-pregnant BMI, previous history of hypertension, height, exercise, dairy consumption, red meat consumption, parity numbers, cigarette smoking, and weight change at 2 months with an AIC value of 3288.74 and an AUC value of 0.71. CONCLUSIONS: In these analyses, separate models predicting PIH and GDM were better than a combined model predicting PIH or GDM. These final models indicate that we can reasonably identify women who are at increased risk for adverse maternal outcomes associated with hypertensive disorders or diabetes during pregnancy.

The purpose of this hermeneutic phenomenological study was to understand the essence of the lived experience of women after having an abnormal prenatal ultrasound. One hundred years ago, health disciplines had limited therapies for prenatal and neonatal disorders. During this period, the eugenics movement influenced leaders to involuntarily sterilize individuals who were sought to be "unfit" to prevent disorders in offspring. ... One of these contemporary reproductive genetic technologies is the use of ultrasound and serum bio-medical markers for detection of congenital, chromosome, and genetic disorders. When ultrasounds reveal abnormal findings, the perceived perfect pregnancy vanishes and gives way to feelings of shock, disbelief, fear, guilt, loss, and threats to self and their unborn baby. Twelve women who had an abnormal ultrasound were interviewed within the context of their cultural values and beliefs. The method of van Manen's hermeneutic phenomenology illuminated the meaning for these women in their life worlds. ... They endured this experience through their own coping mechanisms, but often felt uncertainty and emotional turmoil until the birth. The women also sought comfort through their cultural values, beliefs, and traditions. In coping with the risks found on this abnormal ultrasound, women often selected silence or blocking perceived threats. With these coping methods, they were alone in their suffering. ... Health providers, in not recognizing these women's misunderstandings and emotional fears, abandoned them in their psychosocial and cultural needs. The significance reveals that nurses and health providers need to infuse human caring ways of being, knowing, and doing within advanced technological environments. / by Jeanne Chatham Gottlieb. / Thesis (Ph.D.)--Florida Atlantic University, 2013. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

Thesis (MSc)--Stellenbosch University, 2003. / ENGLISH ABSTRACT: Introduction Worldwide, up to 25% of women are assaulted during pregnancy, with estimates varying between populations. Violence has been associated with adverse pregnancy outcome, including preterm birth, abruptio placentae and low birth weight. Among the Coloured population of the Western Cape the incidence of spontaneous preterm birth is 20%, compared to the global figure of 10%. Overall, the rate of preterm labour has not dropped over the past 40 years and no clearer answer as to a specific cause has been found. The objective of this study was to determine whether patients who deliver preterm experience more domestic violence than those who deliver at term. Methods Two groups of patients were assessed. Firstly, patients who spontaneously delivered between 24 and 33 weeks (24wOd - 33w6d), who were admitted for suppression of active labour after 24 weeks, or who experienced placental abruption before 34 weeks, were screened for domestic violence using the "Abuse Assessment Screen". A second group of women, attending a local Midwife Obstetric Unit with uncomplicated pregnancies, completed the same questionnaire. The questionnaires were all administered by the same person (J.S.) after written informed consent was given. Results A total of 229 patients were interviewed, 99 in the low risk (LR) and 130 in the preterm labour (PTL) group, which included 23 women with abruptio placentae. The PTL group experienced significantly more violence throughout their lives than the LR group (59.7% vs. 40.4%, p = 0.038). Experiences of violence within the last year or during the pregnancy did not reach statistical significance between the two groups, although the numbers were higher for the PTL group. The PTL group smoked significantly more cigarettes per day (p = 0.009), used more alcohol (p < 0.001) and had a higher incidence of syphilis than the LR group (p = 0.005). These differences remained the same when the abruptio's were analyzed as a separate group. Conclusions: Women who delivered preterm did experience more violence at some point in their lives and were also more likely to engage in high-risk behaviour. Violence alone does not seem to cause PTL directly, but is part of a low socioeconomic lifestyle. The fact that the alcohol use is so high among these women is a problem that needs to be addressed, but once again, it is possibly the result of deeper social problems. The need for education on values and respect, family planning use and low risk sexual behaviour is once again challenged. / AFRIKAANSE OPSOMMING: GEWELD TEEN VROUE -IMPAK OP REPRODUKTIEWE GESONDHEID EN UITKOMS VAN SWANGERSKAP Inleiding Daar word beraam dat tot 25% van alle swanger vroue aangerand word, maar die insidensie wissel tussen verskillende populasies. Ervarings van geweld kan 'n direkte of indirekte oorsaak wees van swak verloskundige uitkoms wat voortydse kraam, abruptio placentae en lae geboortegewig insluit. In die Wes- Kaap, onder die Kleurlingbevolking, is die insidensie van voortydse kraam 20%, wat swak vergelyk met die wêreldwye insidensie van 10%. Gedurende die laaste 40 jaar het die voorkoms van voortydse kraam nie verminder nie en geen deurbrake is gemaak t.o.v die oorsaak van die probleem nie. Die doel van hierdie studie was om te bepaal of vroue wat prematuur verlos moontlik meer geweld ervaar as vroue wat op normale swangerskapsduur verlos. Metodes Twee groepe vroue is bestudeer. Die eerste groep het vroue ingesluit wat spontaan verlos het tussen 24 en 33 weke (24wOd - 33w6d) of vroue wat na 24 weke swangerskapsduur toegelaat is vir onderdrukking van kraam. Vroue met plasentale loslating (abruptio placentae) voor 34 weke, sonder onderliggende hipertensiewe toestande, was ook ingesluit in die groep. Daar is m.b.v. 'n vraelys ("Abuse Assessment Screen") bepaal watter van die vroue gesinsgeweld ervaar het. Die tweede groep het vroue ingesluit met ongekompliseerde swangerskappe en wat by 'n nabygeleë kliniek voorgeboortesorg ontvang het. Hulle is ook gevra om die vraelys te voltooi en is opgevolg om die uitkoms van hulle swangerskappe te noteer. Die vraelyste is almal deur een persoon (J.S.) aan die vroue voorgelê nadat hulle ingeligte, skriftelike toestemming gegee het. Resultate 'n Totaal van 229 vroue was ingesluit, 99 in die lae risiko (LR) groep en 130 in die voortydse kraam (VK) groep, waarvan 23 abruptio placentae gehad het. In vergelyking met die LR groep, het die VK groep het betekenisvol meer geweld in hulle leeftyd ervaar (59.7% teenoor 40.4%, p = 0.038). Geweld wat tydens die afgelope jaar of tydens die swangerskap ervaar is, het nie betekenisvol verskil tussen die twee groepe nie, alhoewel die getalle hoër was vir die VK groep. Die VK groep het betekenisvol meer sigarette per dag gerook (p = 0.009), meer alkohol gebruik (p < 0.001) en het 'n hoër insidensie van sifilis gehad as die LR groep (p = 0.005). Hierdie verskille was steeds beduidend nadat dié met abruptio placentae as 'n aparte groep geanaliseer is. Gevolgtrekking Die vroue wat prematuur verlos het, het meer emosionele en fisiese geweld in hulle leeftyd ervaar en is meer geneig om 'n ongesonde leefstyl te handhaaf. Geweld blyk nie 'n direkte oorsaak van voortydse kraam te wees nie, maar gaan gepaard met 'n lae sosio-ekonomiese lewensstyl. Die hoë insidensie van alkoholgebruik onder swanger vroue is 'n probleem wat aangespreek moet word, maar dit is waarskynlik die manifestasie van dieper emosionele probleme. Opvoeding in terme van waardes en respek, gesinsbeplanning en veilige seksuele gedrag is gevolglik 'n noodsaaklikheid.

Thesis (MMed (Obstetrics and Gynaecology))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: Study objective: To investigate whether an educational intervention in the Gynaecology Department of Tygerberg Hospital (TBH) was effective in improving the accuracy of the diagnosis and appropriateness of treatment options offered to women with suspected Ectopic Pregnancy (EP). Methods: A retrospective cross-sectional before-and-after study was performed, including 335 consecutive patients with suspected EP before (1/3 - 30/6/2008) and after (1/9 - 31/12/2008) “the intervention”. From the gynaecological admissions register all pregnant patients with symptoms potentially compatible with EP were selected and these were cross referenced with beta-hCG requests, entries in the theatre register for surgery for possible EP and methotrexate prescriptions for EP in these time periods. “The intervention” consisted of a formal lecture presented to the registrars and consultants regarding the latest evidence-based guidelines concerning the diagnosis and management of EP. An algorithm based on this information was introduced in the emergency unit and ultrasound unit together with a prescribed ultrasound reporting form containing all the pertinent information required to follow the algorithm. Clinical decisions were left to the registrar and consultant on duty. Primary outcomes: Time from presentation to treatment, number and appropriateness of special investigations, surgical procedures or medical management. Secondary outcomes: Number of in-patient days and visits, adherence to the algorithm. Results: There was a non-significant trend towards improved reporting of the uterine content and significantly less reports of definite signs of an intrauterine pregnancy (IUP) (p<0.001, RR 0.46, 95% CI 0.31-0.70) due to stricter ultrasound criteria being followed. There was a significant change in the spectrum of uterine findings (p=0.001), the spectrum of adnexal findings (p=0.006) and the spectrum of free fluid noted (p=0.05). There was a reduction in the total number of beta-hCG levels requested at presentation (patients with no beta-hCG: 24 vs 34, p=0.05, RR 1.60, 95% CI 0.99-2.59) with a significant reduction in the number of inappropriate beta-hCG requests (77 vs 40, p<0.001, RR 0.60, 95% CI 0.43-0.81). There was a significant difference in the spread of the number of beta-hCG tests per patient with less repeat tests in the study group (p=0.021). Significantly less manual vacuum aspirations (MVAs) were performed (47 vs 21, p=0.003, RR 0.51, 95% CI 0.32-0.81) but there was no change in the other treatment modalities offered nor in the time from presentation to treatment, number of visits or in-patient days. Adherence to the algorithm was poor (59 %). Conclusions: Except for a significant decrease in the MVAs performed, with possibly less interrupted early intrauterine pregnancies, the improvement in the use of special investigations after “the intervention” did not translate into fewer inappropriate diagnoses and management. This could be due to frequent non-adherence to the algorithm, and widespread implementation of the algorithm as well as continuous audits would be necessary before a future study could be attempted to assess the efficacy of the algorithm. / AFRIKAANSE OPSOMMING: Studiedoelwit: Die hoofdoel van hierdie studie is om te ondersoek of „n opvoedkundige intervensie in die Ginekologiese afdeling van Tygerberg Hospitaal (TBH) doeltreffend sou wees in die verbetering van die akkuraatheid van diagnose en die gepastheid van behandelingsopsies wat aan vroue gebied word met „n vermoedelike ektopiese swangerskap (ES). Metodes: „n Retrospektiewe, kruisdeursnee voor-en-na studie rakende 335 opeenvolgende pasiënte wat ‟n vermoedelike ES het voor (1/3/2008 – 30/6/2008) en na (1/9/2008 – 31/12/2008) “die intervensie”. Swanger pasiënte is uit die ginekologiese toelatingsregister geselekteer indien hulle simptome gehad het wat moontlik verbind kon word met ES. Hulle is kruisverwys met die beta-hCG‟s aangevra, inskrywings in die teaterregister vir chirurgie vir moontlike ES en ginekologie-pasiënte wat metotrexate vir ES binne hierdie tydperke ontvang het. “Die intervensie” het bestaan uit „n formele lesing aan die kliniese assistente en konsultante ten opsigte van die jongste bewysgebaseerde riglyne rakende die diagnose en hantering van ES. „n Algoritme gegrond op hierdie inligting is in die noodeenheid en ultraklank-afdeling ten toon gestel asook „n voorgeskrewe ultraklank rapporteringsvorm met al die toepaslike inligting wat vereis word om die algoritme te volg. Kliniese besluite is aan die kliniese assistent en konsultant aan diens oorgelaat. Primêre uitkomste: Tydsduur vanaf aanmelding tot behandeling, aantal en gepastheid van spesiale ondersoeke, chirurgiese prosedures en mediese hantering. Sekondêre uitkomste: Die aantal binnepasiëntdae en besoeke, nakoming van die algoritme. Resultate: Daar was „n nie-betekenisvolle neiging tot beter rapportering van die uteriene-inhoud en betekenisvol minder rapportering van definitiewe tekens van „n intra-uteriene swangerskap (IUS) (p<0.001, RR 0.46, 95% CI 0.31-0.70) as gevolg van strenger ultraklankstandaarde gevolg. Daar was „n betekenisvolle verandering in die spektrum van uteriene bevindinge (p=0.001), die spektrum van die adneksale bevindinge (p=0.006) en die spektrum van die vrye vog aangeteken (p=0.05). Daar was „n vermindering in die totale aantal beta-hCG-vlakke aangevra met aanmelding (pasiënte met geen hCG: 24 vs 34, p=0.05, RR 1.60, 95% CI 0.99-2.59) met „n betekenisvolle vermindering in die aantal onvanpaste beta-hCGs aangevra (77 vs 40, p<0.001, RR0.60, 95% CI 0.43-0.81). Daar was „n betekenisvolle verskil in die verspreiding van die aantal beta-hCG-toetse per pasiënt, met minder herhalende toetse in die studiegroep (p=0.021). Betekenisvol minder manuele vakuum aspirasies (MVAs) is uitgevoer (47 vs 21, p=0.003, RR 0.51, 95% CI 0.32-0.81), maar geen verskil in ander behandelingsmodaliteite is aangebied nie, asook geen verskil in die tydsduur vanaf aanmelding, die aantal besoeke of die aantal binnepatiëntdae nie. Nakoming van die algoritme was swak (59%). Gevolgtrekkings: Behalwe vir „n betekenisvolle afname in die MVAs uitgevoer, met moontlik minder onderbroke vroeë IUS, het die verbetering in die gebruik van spesiale ondersoeke ná “die intervensie” nie minder onvanpaste diagnoses en hantering tot gevolg gehad nie. Dit kan die gevolg wees van gereelde nie-nakoming van die algoritme, en uitgebreide implementering van die algoritme asook voortdurende oudits sal nodig wees voor „n verdere studie aangepak kan word om die doeltreffendheid van die algoritme te bepaal.

Prostate and breast cancer are the leading causes of cancer-related death in men and women, respectively, and metastasis is the primary factor underlying the high mortality rates.1 Snail transcription factor is an important molecule that drives prostate and breast cancer metastasis through the process of epithelial mesenchymal transition (EMT). Proteolytic enzymes that promote invasion and metastasis such as the lysosomal cysteine protease cathepsin L (Cat L) have been shown to degrade E-cadherin, promoting the epithelial mesenchymal transition (EMT).2 It has also been shown that silencing Cat L can inhibit transforming growth factor-beta (TGF-β)-mediated EMT by suppressing Snail transcription factor.3 Several recent studies have highlighted an additional unexpected localization and site of action for Cat L within the nucleus in breast, colon and prostate cancer.4 Natural products have been shown to be efficacious in prevention and possible treatment of cancer.5 Specifically, we have been studying Muscadine Grape Skin Extract (MSKE) as a possible candidate to inhibit Snail signaling. MSKE has previously been shown to promote prostate cancer apoptosis.6 We hypothesized that Snail promotes nuclear localization of Cat L, which promotes EMT associated with increased migration and invasion, and that antagonizing Snail-Cat L signaling would lead to mesenchymal epithelial transition (MET). We showed for the first time that MSKE promotes apoptosis through induction of endoplasmic reticulum stress response and autophagy. Additionally, MSKE could inhibit Snail-mediated EMT via scavenging reactive oxygen species. Moreover, Snail could promote nuclear localization of Cat L, which then promoted cleavage of CDP/Cux, increased Snail transcription and decreased E-cadherin transcription by direct promoter binding of cleaved CDP/Cux, leading to EMT associated with increased migration and invasion. Interestingly, Z-FY-CHO, a small molecule specific inhibitor of Cat L, as well as MSKE could antagonize this signaling by promoting nuclear to cytoplasmic re-localization of Cat L. Therefore, we have dissected novel mechanisms of action of Snail and how it can be antagonized by MSKE natural product.