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Real-time captions appear to be an effective tool in assisting deaf and hard of hearing (DHH) college students' access information and communication in certain classroom settings. However, there is limited knowledge of DHH students' direct experiences with real-time captioning services. In this study, we gathered narratives from 15 DHH college students across the United States about their experiences with real-time captioning services in college. We analyzed the stories using thematic narrative analysis and uncovered 4 types that students told about their experiences. The story types were (a) stories of overcoming obstacles, (b) stories of resignation, (c) pragmatic stories, and (d) stories of personal connection. These story types reveal that although many students eventually experience effective communication access through real-time captioning services, they can initially struggle to overcome barriers to using the services successfully. Making time and space to listen to DHH students' narratives can teach educators and professionals how to support these students and resolve barriers before they arise., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cardiac fibrosis is defined by the excessive accumulation of extracellular matrix (ECM) material resulting in cardiac tissue scarring and dysfunction. While it is commonly accepted that myofibroblasts are the major contributors to ECM deposition in cardiac fibrosis, their origin remains debated. By combining lineage tracing and RNA sequencing, our group made the paradigm-shifting discovery that a subpopulation of resident vascular stem cells residing within the aortic, carotid artery, and femoral aartery adventitia (termed AdvSca1-SM cells) originate from mature vascular smooth muscle cells (SMCs) through an in situ reprogramming process. SMC-to-AdvSca1-SM reprogramming and AdvSca1-SM cell maintenance is dependent on induction and activity of the transcription factor, KLF4. However, the molecular mechanism whereby KLF4 regulates AdvSca1-SM phenotype remains unclear. In the current study, leveraging a highly specific AdvSca1-SM cell reporter system, single-cell RNA-sequencing (scRNA-seq), and spatial transcriptomic approaches, we demonstrate the profibrotic differentiation trajectory of coronary artery-associated AdvSca1-SM cells in the setting of Angiotensin II (AngII)-induced cardiac fibrosis. Differentiation was characterized by loss of stemness-related genes, including Klf4 , but gain of expression of a profibrotic phenotype. Importantly, these changes were recapitulated in human cardiac hypertrophic tissue, supporting the translational significance of profibrotic transition of AdvSca1-SM-like cells in human cardiomyopathy. Surprisingly and paradoxically, AdvSca1-SM-specific genetic knockout of Klf4 prior to AngII treatment protected against cardiac inflammation and fibrosis, indicating that Klf4 is essential for the profibrotic response of AdvSca1-SM cells. Overall, our data reveal the contribution of AdvSca1-SM cells to myofibroblasts in the setting of AngII-induced cardiac fibrosis. KLF4 not only maintains the stemness of AdvSca1-SM cells, but also orchestrates their response to profibrotic stimuli, and may serve as a therapeutic target in cardiac fibrosis.

We previously reported that deletion of a 44-nucleotide element in the 3' untranslated region (UTR) of the Chikungunya virus (CHIKV) genome enhances the virulence of CHIKV infection in mice. Here, we find that while this 44-nucleotide deletion enhances CHIKV fitness in murine embryonic fibroblasts in a manner independent of the type I interferon response, the same mutation decreases viral fitness in C6/36 mosquito cells. Further, the fitness advantage conferred by the UTR deletion in mammalian cells is maintained in vivo in a mouse model of CHIKV dissemination. Finally, SHAPE-MaP analysis of the CHIKV 3' UTR revealed this 44-nucleotide element forms a distinctive two-stem-loop structure that is ablated in the mutant 3' UTR without altering additional 3' UTR RNA secondary structures.

We previously established that vascular smooth muscle-derived adventitial progenitor cells (AdvSca1-SM) preferentially differentiate into myofibroblasts and contribute to fibrosis in response to acute vascular injury. However, the role of these progenitor cells in chronic atherosclerosis has not been defined. Using an AdvSca1-SM cell lineage tracing model, scRNA-Seq, flow cytometry, and histological approaches, we confirmed that AdvSca1-SM-derived cells localized throughout the vessel wall and atherosclerotic plaques, where they primarily differentiated into fibroblasts, smooth muscle cells (SMC), or remained in a stem-like state. Krüppel-like factor 4 (Klf4) knockout specifically in AdvSca1-SM cells induced transition to a more collagen-enriched fibroblast phenotype compared with WT mice. Additionally, Klf4 deletion drastically modified the phenotypes of non-AdvSca1-SM-derived cells, resulting in more contractile SMC and atheroprotective macrophages. Functionally, overall plaque burden was not altered with Klf4 deletion, but multiple indices of plaque composition complexity, including necrotic core area, macrophage accumulation, and fibrous cap thickness, were reduced. Collectively, these data support that modulation of AdvSca1-SM cells through KLF4 depletion confers increased protection from the development of potentially unstable atherosclerotic plaques.

Background: In recent years, fate-mapping lineage studies in mouse models have led to major advances in vascular biology by allowing investigators to track specific cell populations in vivo. One of the most frequently used lineage tracing approaches involves tamoxifen-inducible Cre ERT -LoxP systems. However, tamoxifen treatment can also promote effects independent of Cre recombinase activation, many of which have not been fully explored., Methods: To elucidate off-target effects of tamoxifen, male and female mice were either unmanipulated or injected with tamoxifen or corn oil. All mice received PCSK9 (proprotein convertase subtilisin/kexin type 9)-AAV (adeno-associated virus) injections and a modified Western diet to induce hypercholesterolemia. After 2 weeks, serum cholesterol and liver morphology were assessed. To determine the duration of any tamoxifen effects in long-term atherosclerosis experiments, mice received either 12 days of tamoxifen at baseline or 12 days plus 2 sets of 5-day tamoxifen boosters; all mice received PCSK9-AAV injections and a modified Western diet to induce hypercholesterolemia. After 24 weeks, serum cholesterol and aortic sinus plaque burden were measured., Results: After 2 weeks of atherogenic treatment, mice injected with tamoxifen demonstrated significantly reduced serum cholesterol levels compared with uninjected- or corn oil-treated mice. However, there were no differences in PCSK9-mediated knockdown of LDL (low-density lipoprotein) receptors between the groups. Additionally, tamoxifen-treated mice exhibited significantly increased hepatic lipid accumulation compared with the other groups. Finally, the effects of tamoxifen remained for at least 8 weeks after completion of injections, with mice demonstrating persistent decreased serum cholesterol and impaired atherosclerotic plaque formation., Conclusions: In this study, we establish that tamoxifen administration results in decreased serum cholesterol, decreased plaque formation, and increased hepatic lipid accumulation. These alterations represent significant confounding variables in atherosclerosis research, and we urge future investigators to take these findings into consideration when planning and executing their own atherosclerosis experiments., Competing Interests: Disclosures None.

Rapid-cycling bipolar disorder (RCBD) is a phase of bipolar disorder defined by the presence of ≥ 4 mood episodes in a year. It is a common phenomenon characterized by greater severity, a predominance of depression, higher levels of disability, and poorer overall outcomes. It is resistant to treatment by conventional pharmacotherapy. The existing literature underlines the scarcity of evi-dence and the gaps in knowledge about the optimal treatment strategies for RCBD. However, most reviews have considered only pharmacological treatment options for RCBD. Given the treatment-refractory nature of RCBD, nonpharmacological interventions could augment medications but have not been adequately examined. This review carried out an updated and comprehensive search for evidence regarding the role of nonpharmacological therapies as adjuncts to medications in RCBD. We identified 83 reviews and meta-analyses concerning the treatment of RCBD. Additionally, we found 42 reports on adjunctive nonpharmacological treatments in RCBD. Most of the evidence favoured concomitant electroconvulsive therapy as an acute and maintenance treatment. There was pre-liminary evidence to suggest that chronotherapeutic treatments can provide better outcomes when combined with medications. The research on adjunctive psychotherapy was particularly scarce but suggested that psychoeducation, cognitive behavioural therapy, family interventions, and supportive psychotherapy may be helpful. The overall quality of evidence was poor and suffered from several methodological shortcomings. There is a need for more methodologically sound research in this area, although clinicians can use the existing evidence to select and individualize nonpharmacological treatment options for better management of RCBD. Patient summaries are included to highlight some of the issues concerning the implementation of adjunctive nonpharmacological treatments., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Vascular smooth muscle-derived Sca1+ adventitial progenitor (AdvSca1-SM) cells are tissue-resident, multipotent stem cells that contribute to progression of vascular remodeling and fibrosis. Upon acute vascular injury, AdvSca1-SM cells differentiate into myofibroblasts and are embedded in perivascular collagen and the extracellular matrix. While the phenotypic properties of AdvSca1-SM-derived myofibroblasts have been defined, the underlying epigenetic regulators driving the AdvSca1-SM-to-myofibroblast transition are unclear. We show that the chromatin remodeler Smarca4/Brg1 facilitates AdvSca1-SM myofibroblast differentiation. Brg1 mRNA and protein were upregulated in AdvSca1-SM cells after acute vascular injury, and pharmacological inhibition of Brg1 by the small molecule PFI-3 attenuated perivascular fibrosis and adventitial expansion. TGF-β1 stimulation of AdvSca1-SM cells in vitro reduced expression of stemness genes while inducing expression of myofibroblast genes that was associated with enhanced contractility; PFI blocked TGF-β1-induced phenotypic transition. Similarly, genetic knockdown of Brg1 in vivo reduced adventitial remodeling and fibrosis and reversed AdvSca1-SM-to-myofibroblast transition in vitro. Mechanistically, TGF-β1 promoted redistribution of Brg1 from distal intergenic sites of stemness genes and recruitment to promoter regions of myofibroblast-related genes, which was blocked by PFI-3. These data provide insight into epigenetic regulation of resident vascular progenitor cell differentiation and support that manipulating the AdvSca1-SM phenotype will provide antifibrotic clinical benefits.

Introduction: Patients with functional neurological disorders (FND) present with weakness, sensory or movement disorder without corresponding brain pathology. The current classificatory systems suggest an inclusionary approach to diagnose FND. Hence, there is a need to systematically evaluate the diagnostic accuracy of clinical signs and electrophysiological investigations in view of the lack of gold standard tests to diagnose FND., Methods: PubMed and SCOPUS databases were searched for studies published from Jan 1950 to Jan 2022 which reported the diagnostic accuracy of clinical signs and electrophysiological investigations in patients with FND. The Newcastle Ottawa scale was used to assess the quality of the studies., Results: Twenty-one studies (727 cases and 932 controls), of which 16 reported clinical signs and, five reported electrophysiological investigations, were included in the review. Two studies were of good quality, 17 of moderate quality, and two of poor quality. We identified 46 clinical signs (24 in weakness, 3 in sensory, and 19 in movement disorders) and 17 investigations (all in movement disorders). Specificity values for signs and investigations were comparatively high compared to the wide variance in sensitivity values., Conclusion: Electrophysiological investigations appear to have a promising role in diagnosing FND, particularly functional movement disorders. The combined use of individual clinical signs and electrophysiological investigations may support and improve diagnostic certainty of FND. Future research can focus on improving the methodology and validating the existing clinical signs and electrophysiological investigations to enhance the validity of the composite diagnostic criterias for FND diagnosis., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: An essential part of pediatric dentistry in recent times is age estimation for various purposes such as orthodontics, forensic dentistry, human anthropology, and bioarchaeology. Assessment of calcification of dental tissue is another physiologic method for skeletal growth assessment., Aims: This study aims to evaluate the correlation between dental calcification stages and skeletal maturity indicators and their application in age estimation purposes., Methods: Tooth calcification was assessed by Demirjian's method and hand-wrist assessment was done by Fishman's method. Spearman's rank-order correlation coefficient was applied to measure the association between skeletal maturational indicators and dental calcification stages of individual teeth, and the statistical significance of the correlation was tested., Results: Spearman's significant coefficients for canine, first premolar, second premolar, and molar are 0.11, 0.09, 0.09, and 0.13, respectively, which are not significant., Conclusion: Fishman's method of hand-wrist radiograph assessment is quite accurate as a maturity indicator but its association with dental calcification stages cannot be established., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Kumari et al.)

Competing Interests: The authors have no conflicts of interest or financial disclosures to report.

Cardiovascular diseases are characterized by chronic vascular dysfunction and provoke pathological remodelling events, such as neointima formation, atherosclerotic lesion development, and adventitial fibrosis. While lineage-tracing studies have shown that phenotypically modulated smooth muscle cells (SMCs) are the major cellular component of neointimal lesions, the cellular origins and microenvironmental signalling mechanisms that underlie remodelling along the adventitial vascular layer are not fully understood. However, a growing body of evidence supports a unique population of adventitial lineage-restricted progenitor cells expressing the stem cell marker, stem cell antigen-1 (Sca1; AdvSca1 cells) as important effectors of adventitial remodelling and suggests that they are at least partially responsible for subsequent pathological changes that occur in the media and intima. AdvSca1 cells are being studied in murine models of atherosclerosis, perivascular fibrosis, and neointima formation in response to acute vascular injury. Depending on the experimental conditions, AdvSca1 cells exhibit the capacity to differentiate into SMCs, endothelial cells, chondrocytes, adipocytes, and pro-remodelling cells, such as myofibroblasts and macrophages. These data indicate that AdvSca1 cells may be a targetable cell population to influence the outcomes of pathologic vascular remodelling. Important questions remain regarding the origins of AdvSca1 cells and the essential signalling mechanisms and microenvironmental factors that regulate both maintenance of their stem-like, progenitor phenotype and their differentiation into lineage-specified cell types. Adding complexity to the story, recent data indicate that the collective population of adventitial progenitor cells is likely composed of several smaller, lineage-restricted subpopulations, which are not fully defined by their transcriptomic profile and differentiation capabilities. The aim of this review is to outline the heterogeneity of Sca1+ adventitial progenitor cells, summarize their role in vascular homeostasis and remodelling, and comment on their translational relevance in humans., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Freestyle skiers must optimize their aerial performance by maintaining the strength and coordination to propel themselves in the air and adapt to landings and take-offs on uneven surfaces. The purpose of this study was to investigate the differences in areal bone mineral density (aBMD) and body composition in freestyle skiers and non-freestyle skiing controls. We hypothesized that the unique demands and summation of forces experienced by freestyle athletes would manifest as greater femoral neck aBMD, lower percent body fat, and lower Body Mass Index (BMI) than non-freestyle skiing controls. This is a retrospective cohort study., Methods: Eighteen freestyle skiers (14 M 4 F, [27.56±5.22 years]) and 15 controls (7 M 8 F, [26.93±3.54 years]) were measured with dual energy X-ray absorptiometry (DXA) to determine total body composition, hip and lumbar spine aBMD, and bone mineral composition (BMC). Height and weight were measured with an in-office stadiometer and scale. Questionnaires were used to determine physical activity and pertinent medical history. Between-group variations were analyzed with an analysis of variance (ANOVA) and stratified by sex., Results: Percent body fat, hip and lumbar spine aBMD, BMC, and area were all similar between freeski and non-freeski athletes (P<0.05 for all). BMI was significantly lower in male freeski athletes (23.97 kg/m 2 , 95% CI: 22.75-25.18) compared to non-freestyle skiing controls (26.64 kg/m 2 , 95% CI: 24.43-28.86) (P=0.03)., Conclusions: Freestyle skiers have a lower BMI than non-freestyle skiers. All skiers in this study have similar percent body fat, aBMD, and BMC. This pilot study supports that there are unique musculoskeletal adaptations based on type of skiing. Skiers endure a variety of intense physical forces yet remain understudied despite high orthopedic injury rates. This study serves to broaden the current sports health literature and explore the physical demands and subsequent physiology of freestyle skiers.

Competing Interests: Declaration of Conflicting Interests: The authors declare no potential conflicts of interest concerning the research, authorship, and publication of this article.

Competing Interests: There are no conflicts of interest.

The risk of neutropenia decreases significantly after the first year of clozapine initiation, and indefinite hematological monitoring is increasingly questioned. Despite comparable risks of neutropenia, the guidelines for antithyroid drugs - carbimazole and propylthiouracil do not recommend routine hematological monitoring. Assuming a similar pathogenic mechanism, data from antithyroid drugs indicate that neutropenia develops rapidly, and indefinite hematological monitoring misses a large majority of cases in the pre-symptomatic phase. Hence, a more pragmatic strategy of intensive hematological monitoring in the first year of clozapine initiation followed by selective haematological monitoring in case of febrile illnesses or pharyngitis needs to be explored., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Resident vascular adventitial SCA1+ progenitor (AdvSca1) cells are essential in vascular development and injury. However, the heterogeneity of AdvSca1 cells presents a unique challenge in understanding signaling pathways orchestrating their behavior in homeostasis and injury responses. Using smooth muscle cell (SMC) lineage-tracing models, we identified a subpopulation of AdvSca1 cells (AdvSca1-SM) originating from mature SMCs that undergo reprogramming in situ and exhibit a multipotent phenotype. Here we employed lineage tracing and RNA-sequencing to define the signaling pathways regulating SMC-to-AdvSca1-SM cell reprogramming and AdvSca1-SM progenitor cell phenotype. Unbiased hierarchical clustering revealed that genes related to hedgehog/WNT/beta-catenin signaling were significantly enriched in AdvSca1-SM cells, emphasizing the importance of this signaling axis in the reprogramming event. Leveraging AdvSca1-SM-specific expression of GLI-Kruppel family member GLI1 (Gli1), we generated Gli1-CreERT2-ROSA26-YFP reporter mice to selectively track AdvSca1-SM cells. We demonstrated that physiologically relevant vascular injury or AdvSca1-SM cell-specific Kruppel-like factor 4 (Klf4) depletion facilitated the proliferation and differentiation of AdvSca1-SM cells to a profibrotic myofibroblast phenotype rather than macrophages. Surprisingly, AdvSca1-SM cells selectively contributed to adventitial remodeling and fibrosis but little to neointima formation. Together, these findings strongly support therapeutics aimed at preserving the AdvSca1-SM cell phenotype as a viable antifibrotic approach.

Objective: Our recent work demonstrates that PTEN (phosphatase and tensin homolog) is an important regulator of smooth muscle cell (SMC) phenotype. SMC-specific PTEN deletion promotes spontaneous vascular remodeling and PTEN loss correlates with increased atherosclerotic lesion severity in human coronary arteries. In mice, PTEN overexpression reduces plaque area and preserves SMC contractile protein expression in atherosclerosis and blunts Ang II (angiotensin II)-induced pathological vascular remodeling, suggesting that pharmacological PTEN upregulation could be a novel therapeutic approach to treat vascular disease. Approach and Results: To identify novel PTEN activators, we conducted a high-throughput screen using a fluorescence based PTEN promoter-reporter assay. After screening ≈3400 compounds, 11 hit compounds were chosen based on level of activity and mechanism of action. Following in vitro confirmation, we focused on 5-azacytidine, a DNMT1 (DNA methyltransferase-1) inhibitor, for further analysis. In addition to PTEN upregulation, 5-azacytidine treatment increased expression of genes associated with a differentiated SMC phenotype. 5-Azacytidine treatment also maintained contractile gene expression and reduced inflammatory cytokine expression after PDGF (platelet-derived growth factor) stimulation, suggesting 5-azacytidine blocks PDGF-induced SMC de-differentiation. However, these protective effects were lost in PTEN-deficient SMCs. These findings were confirmed in vivo using carotid ligation in SMC-specific PTEN knockout mice treated with 5-azacytidine. In wild type controls, 5-azacytidine reduced neointimal formation and inflammation while maintaining contractile protein expression. In contrast, 5-azacytidine was ineffective in PTEN knockout mice, indicating that the protective effects of 5-azacytidine are mediated through SMC PTEN upregulation., Conclusions: Our data indicates 5-azacytidine upregulates PTEN expression in SMCs, promoting maintenance of SMC differentiation and reducing pathological vascular remodeling in a PTEN-dependent manner.

Electroconvulsive therapy (ECT) is an effective modality of treatment for a variety of psychiatric disorders. However, it has always been accused of being a coercive, unethical, and dangerous modality of treatment. The dangerousness of ECT has been mainly attributed to its claimed ability to cause brain damage. This narrative review aims to provide an update of the evidence with regard to whether the practice of ECT is associated with damage to the brain. An accepted definition of brain damage remains elusive. There are also ethical and technical problems in designing studies that look at this question specifically. Thus, even though there are newer technological tools and innovations, any review attempting to answer this question would have to take recourse to indirect methods. These include structural, functional, and metabolic neuroimaging; body fluid biochemical marker studies; and follow-up studies of cognitive impairment and incidence of dementia in people who have received ECT among others. The review of literature and present evidence suggests that ECT has a demonstrable impact on the structure and function of the brain. However, there is a lack of evidence at present to suggest that ECT causes brain damage., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Psychiatry.)

Objective: This study was designed to assess the impact of public health policy in Australia in response to the coronavirus disease identified in 2019 (COVID-19) pandemic on the delivery of neurosurgical services. Being essential services, we postulated that there would not be a decrease in elective and emergency neurosurgical presentations and surgeries., Methods: This is a prospective, observational, epidemiologic study in strict adherence to the "STROBE" (Strengthening The Reporting of OBservational studies in Epidemiology) guidelines. It is a cross-sectional, multicentric study involving 5 tertiary neurosurgical centers to capture all public neurosurgical admissions in Queensland during the past 3 months (February-April, 2020) of significant public health policy changes to combat COVID-19., Results: An analysis of the 1298 admissions for the Queensland population of 5.07 million Australians demonstrated a decrease in the number of elective and emergency admissions. The decline in elective admissions, particularly degenerative spine, benign neoplasms, and vascular pathologies, was a direct response of government strategy to curb activity to urgent surgical interventions only. Moreover, a trend toward fewer emergency admissions was also noted, partly explained by less trauma and also a decline in vascular pathologies including subarachnoid hemorrhage., Conclusions: In comparison with Europe and North America, this study demonstrates the impact of proactive public health measures in Australia that successfully flattened the COVID-19 curve while facilitating ongoing care of acutely unwell neurosurgical patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Pathological vascular remodeling and excessive perivascular fibrosis are major contributors to reduced vessel compliance that exacerbates cardiovascular diseases, for instance, promoting clinically relevant myocardial remodeling. Inflammation plays a significant role in both pathological vascular remodeling and fibrosis. We previously demonstrated that smooth muscle cell-specific PTEN depletion promotes significant vascular fibrosis and accumulation of inflammatory cells. In the current study, we aimed to determine the beneficial role of systemic PTEN elevation on Ang II (angiotensin II)-induced vascular fibrosis and remodeling. Approach and Results: Transgenic mice carrying additional copies of the wild-type Pten gene (super PTEN [sPTEN]) and WT littermates were subjected to Ang II or saline infusion for 14 or 28 days. Compared with WT, Ang II-induced vascular fibrosis was significantly blunted in sPTEN mice, as shown by histochemical stainings and label-free second harmonic generation imaging. The protection against Ang II was recapitulated in sPTEN mice bearing WT bone marrow but not in WT mice reconstituted with sPTEN bone marrow. Ang II-induced elevation of profibrotic and proinflammatory gene expression observed in WT mice was blocked in aortic tissue of sPTEN mice. Immunofluorescent staining and flow cytometry both indicated that perivascular infiltration of T cells and macrophages was significantly inhibited in sPTEN mice. In vitro induction of PTEN expression suppressed Ang II-induced Ccl2 expression in vascular smooth muscle cells., Conclusions: Systemic PTEN elevation mediates protection against Ang II-induced vascular inflammation and fibrosis predominantly through effects in resident vascular cells. Our data highly support that pharmacological upregulation of PTEN could be a novel and viable approach for the treatment of pathological vascular fibrosis.

Objective: To recruit South Asian pregnant women, living in the UK, into a clinicoepidemiological study for the collection of lifestyle survey data and antenatal blood and to retain the women for the later collection of cord blood and meconium samples from their babies for biochemical analysis., Design: A longitudinal study recruiting pregnant women of South Asian and Caucasian origin living in the UK., Setting: Recruitment of the participants, collection of clinical samples and survey data took place at the 2 sites within a single UK Northern Hospital Trust., Participants: Pregnant women of South Asian origin (study group, n=98) and of Caucasian origin (comparison group, n=38) living in Leeds, UK., Results: Among the participants approached, 81% agreed to take part in the study while a 'direct approach' method was followed. The retention rate of the participants was a remarkable 93.4%. The main challenges in recruiting the ethnic minority participants were their cultural and religious conservativeness, language barrier, lack of interest and feeling of extra 'stress' in taking part in research. The chief investigator developed an innovative participant retention method, associated with the women's cultural and religious practices. The method proved useful in retaining the participants for about 5 months and in enabling successful collection of clinical samples from the same mother-baby pairs. The collection of clinical samples and lifestyle data exceeded the calculated sample size required to give the study sufficient power. The numbers of samples obtained were: maternal blood (n=171), cord blood (n=38), meconium (n=176), lifestyle questionnaire data (n=136) and postnatal records (n=136)., Conclusions: Recruitment and retention of participants, according to the calculated sample size, ensured sufficient power and success for a clinicoepidemiological study. Results suggest that development of trust and confidence between the participant and the researcher is the key to the success of a clinical and epidemiological study involving ethnic minorities., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Patients with chronic gastro-oesophageal reflux disease experience the reflux of acid and bile into the distal oesophagus. The secondary bile salt sodium deoxycholate (NDC) is implicated in the induction of mucosal injury during reflux episodes. This study hypothesized that NDC damages DNA in oesophageal cells by an oxidative mechanism. In the oesophageal cell line HET1-A, increased production of nitric oxide (NO) was measured in NDC-treated cells. Protection from DNA strand breaks induced by NDC (10 microm) was observed in cells coincubated with the nitric oxide scavenger C-PTIO (p<0.012) or pre-incubated with the NO synthase inhibitor L-NAME (p<0.009) or the NFkappaB inhibitor, TPCK (p<0.036). Collectively these data implicate the involvement of NFkappaB and nitric oxide synthase in the DNA damage induced by NDC in oesophageal cells. In conclusion, NDC-driven NO production may play an important role in inducing DNA damage during episodes of gastro-oesophageal reflux and thereby contribute to reflux-related carcinogenesis.

Barrett's oesophagus is an acquired precancerous condition that develops from mucosal injury incurred due to chronic gastro-oesophageal reflux. The aim of this study was to determine if bile and/or acid components of the refluxate can induce DNA damage in vitro. The oesophageal cell lines FLO-1 and HET1-A were exposed to primary bile salts, individually or as a mixture, and the secondary bile salt sodium deoxycholate, in neutral or acidified media. Cells were then examined in the comet assay to measure DNA strand breaks. Cell viability was also monitored. Acidified media induced DNA damage in a pH- and time-dependent manner. The primary bile compounds sodium glycocholate, glycocholic acid, sodium taurocholate and taurochenodeoxycholate, as an equimolar mixture (100 microM), caused a small but significant (P < 0.028) elevation in DNA damage, but only at neutral pH in FLO-1 cells. Sodium deoxycholate (100 microM) caused a significant (P < 0.008) elevation in DNA damage in both cell lines, but again only at neutral pH. These data suggest that specific components of gastro-oesophageal refluxate are capable of causing DNA damage and may participate in the genesis and progression of Barrett's oesophagus via this mechanism.