Molar pregnancy and co-existent foetus: A report of two cases

Molar pregnancy with a co-existent foetus will lead to preterm labour, severe preeclampsia or bleeding in most of the cases and may need urgent intervention. However, if it does not become complicated with preeclampsia or preterm Labour, the outcome is usually good, with minimal post partum complications and so such pregnancies can be managed with watchful waiting and close observation. The first case was a 29 year-old at 19 weeks of gestation, with hypertension, oedema and severe epigastric pain. Karyotypic assessment of the contents of the uterus revealed a 46-XX foetus with no chromosomal abnormality, as well as the molar placenta also suggesting a complete mole with 46-XX. The second case was a 19 year old woman in labour. A pathological study of the delivered contents of the uterus revealed a complete hydatidiform mole and a normal placenta

Engineered antibody and neuropeptide mediated radionuclide targeting in prostate cancer

PhDProstate cancer (PC) is the most common cancer type in men in the western world and to date no definitive stratergy to image PC is avaliable. This thesis explores the possibility of using Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide Receptor (GRP-R) as biomarkers for the targeting and imaging of PC. The development of an imaging radiopharmaceutical to image all stages of PC growth would improve diagnosis, staging and personalised treatment, as present imaging modalities for PC rely largely on anatomical changes to allow visualisation and have limited sensitivity for imaging metastatic spread of the disease. PSMA was selected due to its up-regulation in advanced carcinoma and metastatic disease and GRP-R due to its high levels of expression in the early stages of PC. The hypothesis is that PC can be imaged by a suitably designed radioligand directed against an appropriate molecular target, such as PSMA and GRP-R. Both of these targets were believed to be appropriate as both are present preferntially in prostate tissue and they both internalise when bound by their ligand. To target PSMA, phage libraries were screened for scFv against both cell-expressed PSMA and recombinant PSMA and diabodies were also generated from high binding clones. Several promising candidates were produced which selectively bound to LNCaP cells and PSMA protein in both FACS and ELISA. Diabodies showed improved binding over corresponding scFv’s. In vivo analysis of tumour-bearing mice failed to reveal tumour uptake of either the scFv or the diabody. In vitro analysis suggested that the affinity of the antibody fragments were not sufficiently high. [99mTc]-Demobesin 4 (DB 4), a radiolabelled GRP-R binding peptide was synthesised. Radioligand binding assays performed on a range of androgen-independent and androgen-dependent PC cell lines showed high GRP-R expression in the androgen dependent LNCaP line but also in the androgen-independent cell lines PC3 and DU145. GRP-R expression, measured by RT-PCR to determine the amount of GRP-R RNA, was similar to that seen using radioligand binding assays and similar patterns were observed in autoradiographic studies. In vivo studies on mice bearing the PC xenografts showed tumour uptake and localisation of [99mTc]-DB 4 within one hour. A limited correlation was observed between results obtained in vivo and in vitro. In conclusion, the results were partly consistant with the hypothesis, whereby initial aims for the PSMA project were successfully achieved with generation of scFv and diabodies that specifically bound, however they proved unsuitable as potential imaging agents, perhaps owing to low binding affinity. GRP-R was shown to be an effective candidate for radioimmaging PC which has the potential to descrininate [99mTc]-DB4 uptake between androgen-independent/dependent cells. Thus this radiopharmaceutical may prove a useful imaging agent for early prostate cancer but that further studies are required to assess its usefulness in the androgen-independent stages of the disease

Melatonin pretreated blastocysts along with calcitonin administration improved implantation by upregulation of heparin binding-epidermal growth factor expression in murine endometrium

Objective: Implantation failure is an obstacle in assisted reproduction techniques (ART). Calcitonin is a molecules involved in uterine receptivity and embryo implantation. Melatonin can promote embryo quality and improve implantation. This study examines the effect of pretreatment of blastocysts with melatonin and calcitonin on heparin binding-epidermal growth factor (HB-EGF) expression in murine endometrium. Materials and Methods: In this experimental study, we collected 2-cell embryos from the oviducts of 1.5 day pregnant NMRI mice. Embryos were cultured to the blastocyst in GTM medium with or without 10-9 M melatonin. Pregnant and pseudo-pregnant mice received intraperitoneal (IP) injections of 2 IU calcitonin. After 24 hours, we transferred the cultured blastocysts into the uteri of pseudo-pregnant mice. Two days later, implantation sites were counted and we assessed the levels of HB-EGF mRNA and protein in the uteri of naturally pregnant and pseudo-pregnant mice by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Statistical analysis was performed with one-way ANOVA followed by the Tukey post hoc test. P<0.05 was considered statistically significant. Results: Melatonin pretreatment of blastocysts along with calcitonin administration significantly increased HB-EGF mRNA and protein (P<0.001) in the endometrium of pseudo-pregnant mice. Administration of calcitonin in naturally pregnant mice significantly increased HB-EGF mRNA and protein levels (P<0.001). Compared with the control group (2.6 ± 0.5), the average number of implantation sites in the melatonin group (4.6 ± 0.5, P<0.05) and calcitonin group (7 ± 1, P<0.001) significantly increased. There was a significant increase in implantation sites in the combined melatonin and calcitonin group (8.6 ± 0.5, P<0.001). Calcitonin significantly enhanced calcitonin receptor mRNA (P<0.001) and protein (P<0.05) in the uteri of naturally pregnant and pseudo-pregnant mice. Conclusion: Melatonin pretreated blastocysts along with calcitonin increased HB-EGF expression in the uteri of pseudopregnant mice. Calcitonin administration upregulated HB-EGF in uteri of naturally pregnant mice

Towards reduction of type II theories on SU(3) structure manifolds

We revisit the reduction of type II supergravity on SU(3) structure manifolds, conjectured to lead to gauged N=2 supergravity in 4 dimensions. The reduction proceeds by expanding the invariant 2- and 3-forms of the SU(3) structure as well as the gauge potentials of the type II theory in the same set of forms, the analogues of harmonic forms in the case of Calabi-Yau reductions. By focussing on the metric sector, we arrive at a list of constraints these expansion forms should satisfy to yield a base point independent reduction. Identifying these constraints is a first step towards a first-principles reduction of type II on SU(3) structure manifolds.Comment: 20 pages; v2: condition (2.13old) on expansion forms weakened, replaced by (2.13new), (2.14new

Impact of a vegan diet on the human salivary microbiota

Abstract Little is known about the effect of long-term diet patterns on the composition and functional potential of the human salivary microbiota. In the present study, we sought to contribute to the ongoing elucidation of dietary effects on the oral microbial community by examining the diversity, composition and functional potential of the salivary microbiota in 160 healthy vegans and omnivores using 16S rRNA gene amplicon sequencing. We further sought to identify bacterial taxa in saliva associated with host inflammatory markers. We show that compositional differences in the salivary microbiota of vegans and omnivores is present at all taxonomic levels below phylum level and includes upper respiratory tract commensals (e.g. Neisseria subflava, Haemophilus parainfluenzae, and Rothia mucilaginosa) and species associated with periodontal disease (e.g. Campylobacter rectus and Porphyromonas endodontalis). Dietary intake of medium chain fatty acids, piscine mono- and polyunsaturated fatty acids, and dietary fibre was associated with bacterial diversity, community structure, as well as relative abundance of several species-level operational taxonomic units. Analysis of imputed genomic potential revealed several metabolic pathways differentially abundant in vegans and omnivores indicating possible effects of macro- and micro-nutrient intake. We also show that certain oral bacteria are associated with the systemic inflammatory state of the host

Robotic assistance during cochlear implantation: the rationale for consistent, controlled speed of electrode array insertion

Cochlear implants (CI) have revolutionized the treatment of patients with severe to profound sensory hearing loss by providing a method of bypassing normal hearing to directly stimulate the auditory nerve. A further advance in the field has been the introduction of “hearing preservation” surgery, whereby the CI electrode array (EA) is carefully inserted to spare damage to the delicate anatomy and function of the cochlea. Preserving residual function of the inner ear allows patients to receive maximal benefit from the CI and to combine CI electric stimulation with acoustic hearing, offering improved postoperative speech, hearing, and quality of life outcomes. However, under the current paradigm of implant surgery, where EAs are inserted by hand, the cochlea cannot be reliably spared from damage. Robotics-assisted EA insertion is an emerging technology that may overcome fundamental human kinetic limitations that prevent consistency in achieving steady and slow EA insertion. This review begins by describing the relationship between EA insertion speed and generation of intracochlear forces and pressures. The various mechanisms by which these intracochlear forces can damage the cochlea and lead to worsened postoperative outcomes are discussed. The constraints of manual insertion technique are compared to robotics-assisted methods, followed by an overview of the current and future state of robotics-assisted EA insertion

A second look at N=1 supersymmetric AdS_4 vacua of type IIA supergravity

We show that a class of type IIA vacua recently found within the N=4 effective approach corresponds to compactification on Ads_4 \times S^3 \times S^3/Z_2^3. The results obtained using the effective method completely match the general ten-dimensional analysis for the existence of N=1 warped compactifications on Ads_4 \times M_6. In particular, we verify that the internal metric is nearly-Kahler and that for specific values of the parameters the Bianchi identity of the RR 2-form is fulfilled without sources. For another range of parameters, including the massless case, the Bianchi identity is satisfied when D6-branes are introduced. Solving the tadpole cancellation conditions in D=4 we are able to find examples of appropriate sets of branes. In the second part of this paper we describe how an example with internal space CP^3 but with non nearly-Kahler metric fits into the general analysis of flux vacua.Comment: Latex file, 35 pages, no figures. Reference added, minor corrections adde

The effect of drinking water pH on the human gut microbiota and glucose regulation:results of a randomized controlled cross-over intervention

Abstract Studies in rodent models have shown that alterations in drinking water pH affect both the composition of the gut microbiota and host glucose regulation. To explore a potential impact of electrochemically reduced alkaline (pH ≈ 9) versus neutral (pH ≈ 7) drinking water (2 L/day) on human intestinal microbiota and host glucose metabolism we conducted a randomized, non-blinded, cross-over study (two 2-week intervention periods, separated by a 3-week wash-out) in 29 healthy, non-smoking Danish men, aged 18 to 35 years, with a body mass index between 20.0 to 27.0 kg m-2. Volunteers were ineligible if they had previously had abdominal surgery, had not been weight stabile for at least two months, had received antibiotic treatment within 2 months, or had a habitual consumption of caloric or artificially sweetened beverages in excess of 1 L/week or an average intake of alcohol in excess of 7 units/week. Microbial DNA was extracted from faecal samples collected at four time points, before and after each intervention, and subjected to 16S rRNA gene amplicon sequencing (Illumina MiSeq, V4 region). Glycaemic regulation was evaluated by means of an oral glucose tolerance test.No differential effect of alkaline versus neutral drinking water was observed for the primary outcome, overall gut microbiota diversity as represented by Shannon’s index. Similarly, neither a differential effect on microbiota richness or community structure was observed. Nor did we observe a differential effect on the abundance of individual operational taxonomic units (OTUs) or genera. However, analyses of within period effects revealed a significant (false discovery rate ≤5%) increase in the relative abundance of 9 OTUs assigned to order Clostridiales, family Ruminococcaceae, genus Bacteroides, and species Prevotella copri, indicating a potential effect of quantitative or qualitative changes in habitual drinking habits. An increase in the concentration of plasma glucose at 30 minutes and the incremental area under the curve of plasma glucose from 0 30 and 0 120 minutes, respectively, was observed when comparing the alkaline to the neutral intervention. However, results did not withstand correction for multiplicity. In contrast to what has been reported in rodents, a change in drinking water pH had no impact on the composition of the gut microbiota or glucose regulation in young male adults. The study is registered at www.clinicaltrials.gov (NCT02917616)