Integrated strategies for investigating endocrine mechanisms in Biomphalaria Glabrata as a test organism for androgenic chemical testing

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London.Endocrine and metabolic disease or dysfunctions are of growing concern in modern societies across the globe, underlining the need for continued focus on the development of pharmaceuticals. Subsequent scientific research has revealed a trend in the increase of such abnormalities and expansion of chemical industries, highlighting concerns that these disorders may, in part, be caused by exposure to environmental pollutants. This has led to changes in legislation concerning chemicals safety testing involving an increasing number of vertebrate animal tests as a part of environmental risk assessment process, at significant financial and ethical costs. A solution that is appropriate and aligned with the three R’s (reduction, refinement and replacement) in relation to animal research is to exploit the use of small invertebrate organisms as possible replacements for mammals. In line with the above approach/solution, this thesis is based on the null hypothesis that common genes, proteins and processes in gastropod molluscs and humans underlie the response of male reproductive organs to androgenic chemicals. Using a freshwater pulmonate snail, Biomphalaria glabrata, physiological effects of two steroid androgens on the development of mollusc secondary sexual organs were studied. Furthermore, an exhaustive investigation on the mollusc nuclear receptor repertoire and reproductive type neuropeptides was conducted. This also included the study of the evolutionary degree of conservation of these genes in non-model molluscs. The results obtained suggest that the snails did not respond to, and were not affected by exposure to the androgens. These results were supported by the absence of the members of subfamily 3C of nuclear receptors, which includes some of the “vertebrate” steroid hormone targets, suggesting that this mollusc may be an inappropriate model for steroid hormone mediated mammalian endocrine function. The nuclear receptor (NR) repertoire of B. glabrata comprised of 39 nuclear receptors representing all the known subfamilies of the NR superfamily. 21 reproductive type neuropeptide genes were identified encoding precursors that are predicted to release over 124 bioactive cleavage products. The consequence of these findings is significant in the context of the development of alternative model organisms for chemical testing as well as elucidating the taxonomic scope of nuclear receptor mediated endocrine disruption

A comparison of buccal versus vaginal misoprostol for induction of labour at term to correlate maternal and foetal outcome

Background: Induction of labour with prostaglandins offers the advantage of promoting cervical ripening with stimulation of myometrial contractility. The use of prostaglandin preparations with or without oxytocin infusion, widely recognized and accepted as a standard method of labour induction, has been shown to reduce induction time and the risk of failed induction. Methods: The present study was a prospective observational study undertaken in the obstetrics and gynaecology department of Adesh Medical College and Hospital, Kurushetra, Haryana, India from 01 June 2023 to 30 November 2023. Total 100 patents were randomly allocated to either group A (n=50) who receive 25 µg misoprostol buccally four hourly upto maximum of four doses, group B (n=50) who receive 25 µg misoprostol vaginally four hourly upto maximum of four doses. Various parameters noted were time interval from induction to vaginally delivery, mode of delivery, maternal adverse effect, and neonatal outcome. Results: The mean induction delivery interval in group I was 14.17 hours and 12.9 hours in group II. The mean number of doses in group I was 1.58±0.36 and 1.26±0.28 in group II. The mode of delivery in group I (buccal) patients was full-term vaginal delivery (FTVD) in 33 of patients, instrumental (forceps) 2 of patients and lower segment caesarean section (LSCS) in 15 of patients. While as in group II (vaginal) patients 35 of patients had FTVD, 1 had instrumental (forceps) and 14 had LSCS. The results of present study were indicated that participants who were treated with buccal misoprostol were suffering from gastrointestinal experiences and tachysystole which was the result of misoprostol dosage. Conclusions: Misoprostol in either buccal or vaginal route has proven to be equally effective for inducing labour in women at term pregnancy. This study found that the women who are treated with buccal misoprostol are suffering from gastrointestinal experiences more than vaginal misoprostol. However, easy intake is observed if the drug is administered buccally outweighs its advantages over the vaginal misoprostol

Diversity and inclusion depend on effective engagement It is everyone’s business to ensure that progress is maintained

Purpose – Highlights some of the things that can be done to ensure that organizations embed diversity and inclusion. Design/methodology/approach – Considers the need for effective engagement, the importance of performance indicators for diversity and inclusion and the key role of sharing stories. Discusses, too, how critical race theory could help to bring about improvements. Findings – Advances the view that a transformational process that supports employees with the knowledge and sustainable skills needed to improve business performance via ethical means will form a significant part of future-proofing organizations. Practical implications – Argues that, to achieve this organizations have to drive home the message that diversity and inclusion are everyone’s business. Social implications – Advances the view that a unified approach to diversity and inclusion, which is embedded in the business ethics of the organization, can have a sustainable positive impact on the health and well-being of individuals, business and society. Originality/value – Considers diversity and inclusion from diverse perspectives and draws conclusions that can help organizations to perform better in these areas

The Nuclear Receptors of Biomphalaria glabrata and Lottia gigantea : Implications for Developing New Model Organisms

Funding: This work was funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Evaluation of ovarian mass in reproductive age group: a 2 years prospective study in a tertiary care hospital in Haryana

Background: In pre-eclampsia, there is increased uteroplacental resistance and reduced fetal perfusion due to inadequate invasion of spiral arterioles by trophoblast cells. This causes impaired fetal growth and fetal hypoxia. The objective was to assess the usefulness of fetal Doppler in predicting adverse perinatal outcome in preeclampsia. Methods: It was a prospective study conducted in Adesh medical college and hospital, Mohri, KKR, Haryana, India during the period of 2 years (2021-2022) on 92 women of reproductive age group from menarche to menopause, attending the hospital with complaints of lower abdomen pain, flatulence, lump in abdomen, changes in urinary and bowel habits and ovarian mass detected on clinical examination, or on ultrasound done for another reason. All details were filled in predesigned Performa. Results: There was a great deal of variation in the occurrence, behaviour, and clinical presentation of ovarian tumors. In addition to physical examination, laboratory investigations such as immunological testing and serum biomarkers and imaging procedures pelvic ultrasonography), can assist to determine the kind of pathology. The diagnosis of non-neoplastic and neoplastic ovarian lesions can be confused due to similar clinical presentations. Ovarian cancers have one of the worst prognoses of any cancer since there is insufficient screening to identify the disease early. Conclusions: It is imperative to raise awareness of this malignancy among Indian women. Because of the diversity of the Indian population, it is necessary to raise awareness of this issue across all linguistic and cultural divides. Not only should early detection be emphasized, but also “how to live well” with the illness should be discussed. All of these sophisticated, more recent diagnostic methods, along with the clinical and histo-morphological factors, can aid in early diagnosis, treatment planning, and prognostic importance.

Impact of simulation-based-teaching in obstetrics and gynecology in under-graduate medical education

Background: Simulation based teaching (SBT) is an evolving teaching-learning method (TLM) that can enhance skill acquisition among students while providing multiple practice sessions, before on-patient implementation helping to improve confidence and competency among medical students. Methods: The study was conducted among 150 students of Phase II MBBS students of Adesh medical college and hospital, KKR, Haryana, from April 2022 to October 2022 on batches of 30 students each during their clinical postings of 4 weeks in the OBG department. They were further divided into batches of 10, and given didactic lecture on the selected topic. Following which, the facilitators demonstrated the skill. The students were allowed to practice individually. There doubts were cleared. An OSCE evaluation of the skill was made, followed by a debriefing session. A feedback form was then filled by both students and facilitators to assess impact of SBT. Results: Among the 150 students of phase II MBBS students, 146 responses were received. Both the medical students and the facilitators showed high levels of satisfaction with SBT. About 60.27% (88) students had a good overall experience with this new TLM. Conclusions: SBT improves retention as well as understanding of the concept. The teachers witnessed improved confidence and enhanced overall performance. The current study concludes that SBT is a highly effective tool and should be firmly inculcated in medical education

A clinical audit of Pap smear test for screening of premalignant and malignant cervical lesions

Background: Cervical cancer, the second most common type of cancer in females, can be easily screened and prevented by Papanicolaou smear test which is a very simple, effective and inexpensive testing modality. The clinical audit aimed to estimate the rate of routine testing as well as the prevalence of various findings of Pap smear tests done at a tertiary level hospital.Methods: It was an analytical cross-sectional study that utilised results of 100 pap smear tests chosen against a set of exclusion and inclusion criteria out of the total 719 pap smears done at Adesh Medical College and Hospital between the duration of 1 January 2022 to 31 May 2022.Results: Only 4.29% of total patients that attended gynaecology OPD got a Pap smear done. A mere 22% patients of those under study came for routine testing. 93% of these 100 patients were negative for intraepithelial lesions, of which 42% were normal, 35% showed non-neoplastic changes and infection was seen in 16% of patients. 7% showed epithelial cell abnormality and 0% had malignant changes.Conclusions: The acceptance of Pap smear for routine screening continues to be low in the Indian setting. There is a massive need to spread awareness among the general public about the importance of Pap smear Test

Russell body cervicitis presenting as endocervical polyp: a case report

Russell body cervicitis has been rarely reported in the literature. Herein, we reported another case of this entity. A 42 years old female patient who presented with postcoital bleeding, a clinical diagnosis of cervical polyp was made which was subsequently biopsied. Histopathological diagnosis of Russell body cervicitis was given followed by positive immunoreactivity for CD138, Kappa and Lambda. Heightened awareness of the existence of this entity may result in reporting of similar cases, which may assist in concluding its pathogenesis and causative agent

Histopathological pattern of endometrial biopsy in abnormal uterine bleeding

Background: Abnormal uterine bleeding is a common complaint in most women of different ages that prompts seeking gynaecologic care. This study aimed to determine the type of endometrial patterns of the different age categories of women who presented as a case of abnormal uterine bleeding. Methods: This was a retrospective study conducted on 72 patients who were presented with abnormal uterine bleeding and had endometrial biopsy done in our hospital. The data on their age, presenting complaints, and comorbidities of all the women were collected. The patterns of endometrial changes were studied and classified in accordance to the FIGO classification. Results: Seventy-two women with abnormal uterine bleeding demonstrated a fluctuating pattern of ten endometrial pathologies distributed among five age groups in the range of 31 to 65 years. Maximum number of cases of AUB were noted in the age group of (36-50) years (56 cases, 77.7%). Most common observed histopathological pattern in this study was normal cyclical patterns including proliferative endometrium (29.16%) and secretory endometrium (22.22%). Conclusions: Histopathological examination of the endometrium shows a clear-cut differentiation between physiological and malignancy changes in the endometrium. Hence, endometrial sampling is considered the golden tool for accurate analysis of the endometrium.

Clinicopathological correlation of abnormal uterine bleeding according to PALM-COEIN classification in reproductive age group in a tertiary care center, North India

Background: AUB is a common problem encountered by women of reproductive age group with increased risk during perimenopausal period. International Federation of Gynecology and Obstetrics (FIGO) has designed a new classification system PALM-COEIN in order to standardize the causes of AUB. Aims and Objectives were to stratify causes of AUB in women of reproductive age group in context to PALM-COEIN classification system. To establish a clinico-pathological correlation among causes of AUB taking aid of radiology wherever required. Methods: All women of reproductive age group presenting with complaints of AUB in department of gynecology from January 2018 to December 2021 were included in the study. The cause were classified based on PALM-COEIN classification both clinically and histopathologically. Radiological investigation was carried out wherever required. Results: Total 560 women of reproductive age group were registered. Majority 321 (57.32%) women were between 41-50 years of age and commonest complaint was heavy menstrual bleeding in 401 (71.60%). PALM and COEIN groups accounted for 40% and 60% respectively. Among structural causes, leiomyoma was the commonest cause 153 (27.32%) of AUB whereas among the functional causes most common was endometrial 188 (33.57%). The clinico-histopathological correlation was statistically significant in cases of AUB-P, AUB-A, AUB-O and AUB-E. Conclusions: The PALM-COEIN classification system helps to understand the causes of AUB and gives simpler terminology, diagnosis and investigations of the causes of AUB and offers better patient management. It can provide better means of quality assurance and appropriateness of treatment