Independent Midwifery practices in Cape Town: birth outcomes and predictors for medical interventions from 2003-2009

Includes bibliographical references.The midwifery model of care is a safe, effective, inexpensive, holistic, woman and baby centered-approach to maternal and infant health. It is widely used in developing and developed world contexts and has proven to have birth outcomes that are comparable to hospital-based, obstetric models. In many settings however, application of the independent midwifery model of care has become increasingly difficult to maintain. Tensions surrounding perceived skills and competencies of midwives, the increasing acceptance of hospital-based, obstetric models of childbirth, controversy over necessity and use of medical interventions, rising insurance premiums, and competition over clients in private sector scenarios are all factors contributing to both low availability and utilization in many countries, including South Africa. In order to consider the role of this model in maternity services in South Africa and to potentially make this model available on a wider scale, it is necessary to understand the demographics of current utilization of existing independent midwifery services, as well their as birth outcomes. This retrospective cohort study documents the total number of deliveries attended by independent midwives, the socio-demographic and reproductive characteristics of women using independent midwives and the birth outcomes and delivery types in the greater Cape Town region among the 16 independent midwives who have practiced during the six and a half year period of January 2003 - end of June 2009. It identifies factors associated with normal vaginal deliveries, instrumental deliveries and caesarean sections, as well as documents the socio-demographic and professional characteristics of the 16 independent midwives. Ethical approval for this research was granted by the University of Cape Town. Anonymous client data was collected from midwifery practices' Maternity Registers and transferred onto a data abstraction sheet. Midwife data was collected via an interviewer-administered questionnaire. All data was entered into Microsoft Excel and analyzed using Stata. The findings of this study will be used to inform maternal and infant health care policy, as well as provide statistics for independent midwives' quality assurance and auditing of services

Extensive remineralization of peatland‐derived dissolved organic carbon and ocean acidification in the Sunda Shelf Sea, Southeast Asia

Southeast Asia is a hotspot of riverine export of terrigenous organic carbon to the ocean, accounting for ∼10% of the global land-to-ocean riverine flux of terrigenous dissolved organic carbon (tDOC). While anthropogenic disturbance is thought to have increased the tDOC loss from peatlands in Southeast Asia, the fate of this tDOC in the marine environment and the potential impacts of its remineralization on coastal ecosystems remain poorly understood. We collected a multi-year biogeochemical time series in the central Sunda Shelf (Singapore Strait), where the seasonal reversal of ocean currents delivers water masses from the South China Sea first before (during Northeast Monsoon) and then after (during Southwest Monsoon) they have mixed with run-off from peatlands on Sumatra. The concentration and stable isotope composition of DOC, and colored dissolved organic matter spectra, reveal a large input of tDOC to our site during Southwest Monsoon. Using isotope mass balance calculations, we show that 60%–70% of the original tDOC input is remineralized in the coastal waters of the Sunda Shelf, causing seasonal acidification. The persistent CO2 oversaturation drives a CO2 efflux of 2.4–4.9 mol m−2 yr−1 from the Singapore Strait, suggesting that a large proportion of the remineralized peatland tDOC is ultimately emitted to the atmosphere. However, incubation experiments show that the remaining 30%–40% tDOC exhibits surprisingly low lability to microbial and photochemical degradation, suggesting that up to 20%–30% of peatland tDOC might be relatively refractory and exported to the open ocean

Deficiency of MicroRNA-181a results in transcriptome-wide cell-specific changes in the kidney and increases blood pressure

MicroRNA miR-181a is downregulated in the kidneys of hypertensive patients and hypertensive mice. In vitro, miR-181a is a posttranslational inhibitor of renin expression, but pleiotropic mechanisms by which miR-181a may influence blood pressure (BP) are unknown. Here, we determined whether deletion of miR-181a/b-1 in vivo changes BP and the molecular mechanisms involved at the single-cell level. We developed a KO (knockout) mouse model lacking miR-181a/b-1 genes using CRISPR/Cas9 technology. Radiotelemetry probes were implanted in 12-week-old C57BL/6J WT (wild type) and miR-181a/b-1 KO mice. Systolic and diastolic BP were 4- to 5-mm Hg higher in KO compared with WT mice over 24 hours (P<0.01). Compared with WT mice, renal renin was higher in the juxtaglomerular cells of KO mice. BP was similar in WT mice on a high- (3.1%) versus low- (0.3%) sodium diet (+0.4 +/- 0.8 mm Hg), but KO mice showed salt sensitivity (+3.3 +/- 0.8 mm Hg; P<0.001). Since microRNAs can target several mRNAs simultaneously, we performed single-nuclei RNA sequencing in 6699 renal cells. We identified 12 distinct types of renal cells, all of which had genes that were dysregulated. This included genes involved in renal fibrosis and inflammation such as Stat4, Col4a1, Cd81, Flt3l, Cxcl16, and Smad4. We observed upregulation of pathways related to the immune system, inflammatory response, reactive oxygen species, and nerve development, consistent with higher tyrosine hydroxylase in the kidney. In conclusion, downregulation of the miR-181a gene led to increased BP and salt sensitivity in mice. This is likely due to an increase in renin expression in juxtaglomerular cells, as well as microRNA-driven pleiotropic effects impacting renal pathways associated with hypertension

High Diagnostic Yield of Whole Exome Sequencing in Participants With Retinal Dystrophies in a Clinical Ophthalmology Setting

To assess the diagnostic yield and the practicality of implementing whole exome sequencing within a clinical ophthalmology setting

A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing

As genome-scale sequencing is increasingly applied in clinical scenarios, a wide variety of genomic findings will be discovered as secondary or incidental findings, and there is debate about how they should be handled. The clinical actionability of such findings varies, necessitating standardized frameworks for a priori decision making about their analysis

An informatics approach to analyzing the incidentalome

Next-generation sequencing (NGS) has transformed genetic research and is poised to revolutionize clinical diagnosis. However, the vast amount of data and inevitable discovery of incidental findings require novel analytic approaches. We therefore implemented for the first time a strategy that utilizes an a priori structured framework and a conservative threshold for selecting clinically relevant incidental findings

肥満糖尿病ラットにおける胃バイパス後の選択的腸管刺激による糖代謝への影響

研究科: 医学薬学府学位:千大院医薬博甲第医1000号要約博士(医学)千葉大

A standardized, evidence-based protocol to assess clinical actionability of genetic disorders associated with genomic variation

Genome and exome sequencing can identify variants unrelated to the primary goal of sequencing. Detecting pathogenic variants associated with an increased risk of a medical disorder enables clinical interventions to improve future health outcomes in patients and their at-risk relatives. The Clinical Genome Resource, or ClinGen, aims to assess clinical actionability of genes and associated disorders as part of a larger effort to build a central resource of information regarding the clinical relevance of genomic variation for use in precision medicine and research

The type II secretion system and its ubiquitous lipoprotein substrate, SsIE are required for biofilm formation and virulence of enteropathogenic escherichia coli

Enteropathogenic Escherichia coli (EPEC) is a major cause of diarrhea in infants in developing countries. We have identified a functional type II secretion system (T2SS) in EPEC that is homologous to the pathway responsible for the secretion of heat-labile enterotoxin by enterotoxigenic E. coli. The wild-type EPEC T2SS was able to secrete a heat-labile enterotoxin reporter, but an isogenic T2SS mutant could not. We showed that the major substrate of the T2SS in EPEC is SslE, an outer membrane lipoprotein (formerly known as YghJ), and that a functional T2SS is essential for biofilm formation by EPEC. T2SS and SslE mutants were arrested at the microcolony stage of biofilm formation, suggesting that the T2SS is involved in the development of mature biofilms and that SslE is a dominant effector of biofilm development. Moreover, the T2SS was required for virulence, as infection of rabbits with a rabbit-specific EPEC strain carrying a mutation in either the T2SS or SslE resulted in significantly reduced intestinal colonization and milder disease

Deregulation of DUX4 and ERG in acute lymphoblastic leukemia

Chromosomal rearrangements deregulating hematopoietic transcription factors are common in acute lymphoblastic leukemia (ALL).1,2 Here, we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG are hallmarks of a subtype of B-progenitor ALL that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression was present in all cases, and was accompanied by transcriptional deregulation of ERG, expression of a novel ERG isoform, ERGalt, and frequent ERG deletion. ERGalt utilizes a non-canonical first exon whose transcription was initiated by DUX4 binding. ERGalt retains the DNA-binding and transactivating domains of ERG, but inhibits wild-type ERG transcriptional activity and is transforming. These results illustrate a unique paradigm of transcription factor deregulation in leukemia, in which DUX4 deregulation results in loss-of-function of ERG, either by deletion or induction of expression of an isoform that is a dominant negative inhibitor of wild type ERG function