Supporting the Biomedical Science UG Project Research Journey Through Staff-Student Partnerships.

Introduction: Developing research skills enhances graduate attributes and student employability. The UG research project is coined the pedagogy of the 21st century but the diversity of supervisory styles is a source of student perceived inequality of experience. The goal of this study was to provide structure and support to undergraduate (UG) biomedical science research students and supervisors by co-creating research informed resources that are accessible, engaging and student centred. We asked 1) How do UG students experience research supervision? 2) What approaches do supervisors use to support UG project students? 3) How do students as partners benefit from being involved in pedagogical research? Materials and Methods: In Stage One, 3 UG student research partners co-developed questionnaires and followed these up with semi-structured interviews. Fifty two UG project students took part in an interactive poll and 14 supervisors answered a questionnaire. Seven students and 4 supervisors were interviewed. These were analysed by thematic analysis. In Stage Two, the questions were asked of UG project students (n = 79) via an interactive poll and the resource developed in Stage One was trialled with students (n = 68) and supervisors (n = 37). Results: The global theme identified was that students feel strongly that the student-supervisor relationship influences their experience, satisfaction and success. In all polls, >90% of students but <60% of supervisors agree that a good student/supervisor partnership has an effect on the success of the final project. A smaller percentage of students felt strongly that they were able to develop a successful partnership with their supervisor. We co-created a visual model and a list of discussion points of how the student-supervisor partnership can be developed, aimed at making supervision more effective whilst being non-prescriptive. Discussion: The resource can be easily adapted. Students believe it helped them to develop a staff-student partnership and supervisors commented that it helps to clarify roles and manage student expectations. This scalable project will support the practice of future UG biomedical science project research students and supervisors. Working with students as partners enabled the development of richer ideas whilst supporting their employability.

Providing HIV Treatment during community-wide flooding: experiences of clients and Health Care Workers in Malawi.

Background: In Malawi, community wide flooding, especially in high HIV burdened districts, continues to affect continuity of care and access to facilities. We explored the lived experiences of clients and healthcare workers (HCWs) to gain understanding of challenges and to propose interventions for improved ART care delivery. Methods: Participants came six health facilities and surrounding communities impacted by flooding between Dec 2021-Apr 2022 in Chikwawa, Nsanje and Mulanje districts in Malawi. Facilities are supported by Partners in Hope, a local NGO and PEPFAR/USAID partner.We conducted In-depth interviews with (IDIs) ART clients identified through medical chart reviews and focus group discussions (FGDs) with HCWs. IDIs and FGDs were coded using inductive and deductive methods in Atlas.ti. Results: We conducted IDIs with 23 respondents, of which, ten were women, ten experienced treatment interruption (>28 days without medication) and 17 relocated from their homes. The Six FGDs involved 37 HCWs. (21 ART providers; 16 lay cadre).In IDIs, most clients who relocated and lost livestock, possessions and ART medications. They travelling for income generation. Barriers to care included dangerous travel conditions, competing needs for time and fear of ill treatment at facilities. Some outreach clinics did not provide ART. Respondents were motivated to remain on care and motivators included fear of developing illnesses and HIV-status acceptance.All providers said that lack of standardized guidelines affected preparedness and response and they advocated for guidelines, stakeholder coordination and adequate resources. Most also reported personal physical exhaustion, damage to their own houses and property, and drug stock-outs. Documentation due to loss of registers was also mostly mentioned. Discussion: Clients motivated to remain in care but face barriers and challenges. National flooding protocols, adequate resource planning and seasonal 6-month ART dispensing may improve ART outcomes.

Aesthetic crown lengthening and lip repositioning surgery: Pre- and post-operative assessment of smile attractiveness.

AIM: To assess the effect of aesthetic crown lengthening (ACL) and lip repositioning surgery (LRS) on perception of smile attractiveness. MATERIALS AND METHODS: Preoperative and 6-month postoperative smile photographs of ACL- or LRS-treated patients were evaluated by 100 raters (five gender-balanced groups of ten per procedure) of diverse background (dental students, general dentists, periodontists and laypersons with and without any aesthetic concerns about their own smile). Smile attractiveness was rated by visual analogue scale (VAS). Multivariate mixed-effect models were applied to determine the effect of procedure, rater (age, gender and group) and case (gingival display and GD) on smile attractiveness rating. RESULTS: Average preoperative and postoperative VAS scores for ACL patients were 3.8 ± 2.0 and 6.2 ± 1.9, respectively. Corresponding LRS patient values were 4.8 ± 2.0 and 6.4 ± 1.9. Treatment, baseline GD and rater age were significant determinants (p < .001) of smile attractiveness for both procedures. Rater gender was not significant. Rater group was significant (p < .032) only for ACL. Procedure (p < .001), baseline VAS (p < .001), change in GD (p ≤ .002) and rater age (p ≤ .017) were significant determinants of smile attractiveness change from preoperative to postoperative. CONCLUSIONS: ACL and LRS are two periodontal plastic surgery procedures that deliver significant smile attractiveness improvements, in the eyes of both laypersons and dental professionals.

Survival of enterococci during hospital laundry processing.

Much remains to be elucidated about the epidemiology of nosocomial enterococcal infections. Enterococci are, however, known to be relatively thermotolerant, and several studies have shown that under laboratory conditions many strains are able to survive the time/temperature combinations of the UK Department of Health recommendations for the decontamination of used linen (HSG(95)18). We therefore wished to investigate the efficacy of decontamination of enterococci from hospital linen in working hospital laundries. The thermotolerance of 40 strains of Enterococcus faecalis and Enterococcus faecium was first determined. Reduction by a factor of greater than 10(5) was achieved in only two of 40 strains after 3 min at 71 degrees C or 10 min at 65 degrees C, the time/temperature combinations specified by the Department of Health for the disinfection of used linen. During experimental challenge of 10 working hospital laundries, however, we demonstrated successful decontamination of laundry artificially contaminated with enterococci. This was shown to take place during the washing stage. Our study suggests that, despite the relative thermotolerance of enterococci, the time/temperature combinations specified in HSG(95)18 should be adequate for their decontamination in hospital laundries.

Alizarin-beta-D-galactoside: a new substrate for the detection of bacterial beta-galactosidase.

We describe the synthesis of a new substrate for the detection of bacterial beta-galactosidase. This substrate, alizarin-beta-D-galactoside, is readily hydrolysed to release alizarin which complexes with various metal ions to form brightly coloured chelates. A total of 367 strains of Gram-negative bacteria were examined for their ability to hydrolyse three chromogenic substrates: alizarin-beta-D-galactoside (Aliz-gal), cyclohexenoesculetin-beta-D-galactoside (CHE-gal) and 5-bromo-4-chloro-3-indolyl-beta-D-galactoside (X-gal). A total of 182 strains (49.6%) were found to hydrolyse at least one of the three substrates. All of these 182 strains (100%) hydrolysed Aliz-gal whereas only 170 (93.4%) and 173 (95.1%) hydrolysed CHE-gal and X-gal, respectively. We conclude that alizarin-beta-D-galactoside is a highly sensitive substrate for the demonstration of beta-galactosidase.

Evaluation of tube coagulase and a fluorogenic substrate for rapid detection of methicillin-resistant Staphylococcus aureus from selective enrichment broth in an outbreak of EMRSA 15.

We investigated the use of tube coagulase and a fluorescent substrate, N-t-BOC-val-pro-arg-7-amido-4-methylcoumarin for the rapid detection of MRSA in selective broth enrichment cultures during an outbreak. These methods were compared with direct plating of swabs and plating a selective broth enrichment culture using 200 screening swabs collected from forty patients during the investigation of an outbreak of E-MRSA 15. Overall 66 swabs were positive for MRSA following subculture of broth enrichment culture. Direct plating detected 25 (38%) positives, tube coagulase 37 (56%), and fluorescent substrate 49 (74%) respectively, although nine of the 49 turned out to be false reactions. When detection from individual patients was analyzed, selective broth subculture identified 28 patients colonized with MRSA. Direct plating detected only 12 (43%) of these patients. The tube coagulase and fluorescence methods detected MRSA in 17 (60%) and 19 (68%) patients respectively. The tube coagulase method was found to be 100% specific for MRSA suggesting its use as a rapid method for the detection of MRSA from selective enrichment broth.

Sensory urgency: how full is your bladder?

OBJECTIVE: To investigate whether women with sensory urgency have an abnormal perception of bladder fullness. DESIGN: Prospective observational study. SETTING: Urodynamic Unit, St George's Hospital, London. SUBJECTS: 15 women with sensory urgency, 15 women with idiopathic detrusor instability and 15 without symptoms of frequency or urgency (control group). INTERVENTIONS: All the women attended for cystometry. Each was asked to complete a visual analogue score of how full she perceived her bladder to be on a scale from 1 to 10. This was done before filling cystometry and at three times during bladder filling. At each time actual filled volume was noted. MAIN OUTCOME MEASURES: Maximum bladder capacity and individual perception of bladder fullness. RESULTS: Women with sensory urgency and detrusor instability had similar maximum bladder capacity although values in both groups were significantly lower than in the control group; thus percentage of maximum bladder capacity was used for analysis. Linear regression was performed for each group of patients and a predicted visual analogue score at 25, 50 and 75% of capacity calculated. These were compared between groups by rank analysis of variance. There was no significant difference between sensory urgency and detrusor instability. However, at 25, 50 and 75% of capacity, both groups had a significantly higher score than the control group. CONCLUSIONS: This abnormal perception would explain symptoms of frequency and urgency in these two groups. These results also confirm the similarity between detrusor instability and sensory urgency.

Efficient replication, integration, and packaging of retroviral vectors with modified long terminal repeats containing the packaging signal.

Retroviral vectors were modified to contain packaging (psi) signals of varying lengths (nucleotides 211-355, 211-565, or 211-1039 of MoMuLV RNA) between the U3-r and U5 sequences of their 5' long terminal repeat (LTR). For the vector MoTN-PR3, containing the full length 211-1039 nucleotide-long psi signal within the 5' LTR, replication, integration, and packaging were almost as efficient as for the original unmodified vector. This result confirmed that the 211-1039 nucleotide-long sequence from the MoMuLV RNA is sufficient and necessary to allow efficient packaging of RNAs. In addition, an important site was revealed where insertion of foreign DNA sequences of up to 829 nucleotides can be made within the 5' LTR, between U3-r and U5 sequences, without affecting viral replication, integration, or packaging.

The Pyridium pad test for diagnosing urinary incontinence. A comparative study of asymptomatic and incontinent women.

Eighteen women with urodynamically proven genuine stress incontinence awaiting surgery and 23 normal, asymptomatic, continent female volunteers took part in a study to compare the accuracy of a qualitative pad test with a quantitative pad-weighing test in detecting urine loss. Each woman took 600 mg of phenazopyridine hydrochloride (Pyridium, Parke-Davis) in three equally divided doses over 18-24 hours and then underwent a standardized, one-hour pad test as described by the International Continence Society. The Pyridium pad test was regarded as positive if there was any orange staining on the pad. The quantitative pad-weighing test was considered positive if there was a weight gain of 1.0 g or more at the end of the one-hour test period. All 18 patients with genuine stress incontinence had positive Pyridium pad tests, and all had pad weight gains of greater than or equal to 1.0 g (mean, 16.5). The maximum pad weight gain in the asymptomatic, continent volunteers was 0.7 g (mean, 0.1), and none was aware of any urinary leakage during the test; however, 12 (52%) had positive Pyridium pad tests. The Pyridium pad test appears 100% sensitive in detecting urine loss in symptomatic women with genuine stress incontinence, but it has a high false-positive rate in healthy, asymptomatic, continent women. If pad-weighing tests are done, the addition of Pyridium generally will not be useful, and if Pyridium is used by itself, the results may be misleading.

Genetic tagging of tumor cells with retrovirus vectors: clonal analysis of tumor growth and metastasis in vivo.

Retrovirus vector infection was used to introduce large numbers of unique genetic markers into tumor cell populations for the purpose of analyzing comparative changes in the clonal composition of metastatic versus that of nonmetastatic tumors during their progressive growth in vivo. The cell lines used were SP1, a nonmetastatic, aneuploid mouse mammary adenocarcinoma, and SP1HU9L, a metastatic variant of SP1. Cells were infected with delta e delta pMoTN, a replication-defective retrovirus vector which possesses the dominant selectable neo gene and crippled long terminal repeats. G418r colonies were obtained at a frequency of 4 x 10(-3). Southern blot analysis of a number of clones provided evidence of random and heritable integration of one or two copies of the proviral DNA. Clonal evolution of primary tumor growth and the nature of lineage relationships among spontaneous metastases and primary tumors were analyzed by subcutaneously injecting 10(5) cells from a pooled mixture of 3.6 x 10(2) G418r SP1HU9L or 10(4) G418r SP1 colonies into syngeneic CBA/J mice. The most striking finding was the relative clonal homogeneity of advanced primary tumors; they invariably consisted of a small number (less than 10) of distinct clones despite the fact that hundreds or thousands of uniquely marked clones had been injected. In the case of the metastatic SP1HU9L cells, the nature of these "dominant" clones varied from one tumor to another. Analysis of a number of lung metastases revealed that a proportion of them were derived from dominant primary tumor clones and were composed of one, and sometimes two, distinct progenitors. In some animals, all the lung metastases were derived from a common progenitor clone, whereas in others, each metastatic nodule had a different progenitor. The results show the following. (i) Retrovirus vector infection can be used to introduce large numbers of unique and stable clonal markers into tumor cell populations. (ii) The progeny of a very limited number of clones dominate in advanced primary tumors. (iii) Mammary carcinoma metastases are of mono- or biclonal origin. The significance of the results is discussed.

Tissue-specific expression of the newly acquired ecotropic Emv-18 provirus in Fv-2 congenic mice.

Expression of endogenous retroviral sequences in Fv-2 congenic mouse strains was examined by Northern blot analysis. Endogenous ecotropic virus transcripts were observed in total spleen RNA of B6.S (Fv-2ss) mice. Endogenous ecotropic transcripts were not detected in spleen RNA of C57BL/6, the Fv-2rr congenic partner of B6.S, nor in spleens of the C57BL/10 (Fv-2rr) and B10.C (Fv-2ss) congenic strains. Mendelian segregation analysis revealed that only backcross mice segregating the newly acquired Fv-2-linked endogenous ecotropic provirus had endogenous ecotropic transcripts in spleen RNA. Examination of different tissues of B6.S mice showed that Emv-18 transcription was highest in spleen and bone marrow, tissues in which Fv-2 has been shown to function. These results support the conclusion that chromosomal location is an important factor controlling Emv-18 expression in B6.S mice. We also report the presence in the spleen of a novel xenotropic virus transcript detectable only in B6.S mice.

Clonal analysis of the late stages of erythroleukemia induced by two distinct strains of Friend leukemia virus.

We observed striking differences between the tumorigenic colony-forming cells present in the spleens of mice late after infection with the anemia-inducing strain of Friend leukemia virus (strain FV-A) and those present after infection with the polycythemia-inducing strain (strain FV-P). Cells within primary colonies derived from FV-A- and FV-P-transformed cells (CFU-FV-A and CFU-FV-P, respectively) contained hemoglobin and spectrin, indicating that the CFU-FV-A and CFU-FV-P were transformed erythroid progenitor cells. The proportion of cells containing hemoglobin was relatively high (> 25%) in newly isolated cell lines derived from CFU-FV-P colonies, whereas cell lines derived from CFU-FV-A colonies had only low levels (0 to 2%) of hemoglobin-containing cells. A high proportion of the cell lines derived from CFU-FV-A colonies responded to pure erythropoietin and accumulated spectrin and hemoglobin, whereas the cell lines derived from CFU-FV-P colonies did not. A cytogenetic analysis indicated that primary CFU-FV-P colony cells were diploid, whereas chromosomal aberrations were observed in the immediate progeny of CFU-FV-A. The presence of unique chromosomal markers in the majority of the cells within individual colonies derived from CFU-FV-A suggested that these colonies originated from single cells. Finally, leukemic progenitor cells transformed by strain FV-A appeared to have an extensive capacity to self-renew (i.e., form secondary colonies in methylcellulose), whereas a significant proportion of the corresponding cells transformed by strain FV-P did not. In addition, the self-renewal capacity of both CFU-FV-A and CFU-FV-P increased as the disease progressed. From these observations, we propose a model for the multistage nature of Friend disease; this model involves clonal evolution and expansion from a differentiating population with limited proliferative capacity to a population with a high capacity for self-renewal and proliferation.