Community-based oral health interventions for people experiencing homelessness: a scoping review.

OBJECTIVE: To determine the characteristics of community-based oral health interventions for people experiencing homelessness. BASIC RESEARCH DESIGN: A scoping review was conducted, adhering to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses: Scoping Reviews) checklist. A search strategy was developed using MeSH terms and key words, and used to search the following electronic databases: Medline/PubMed, CINAHL, ProQuest Assia, Scopus, Web of Science and PsychNet. Key journals and reference lists were also hand-searched. Two reviewers then read the abstracts of all papers, excluding duplicates and papers that did not meet the eligibility criteria. The reviewers then read to full-texts of the studies to be included in the review. RESULTS: Eighteen studies met the inclusion criteria and were included in the study. These studies were predominantly evaluations of community-based dental services or other oral health interventions. Several recommendations were extracted. Interventions should involve co-design with homeless service users; multidisciplinary working, collaboration with dental practitioners, and working with educational establishments. The location of community-based services was also found to be of importance. CONCLUSION: This review has highlighted several recommendations, as well as gaps in the literature. These gaps suggest a need for more non-clinical oral health interventions for the homeless population, and a closer look at the role that non-dental practitioners can play in the delivery of oral health care.

Stereotactic Body Radiotherapy for Large Unresectable Hepatocellular Carcinomas - A Single Institution Phase II Study.

AIMS: To evaluate the safety and efficacy of liver stereotactic body radiotherapy (SBRT) in the treatment of unresectable hepatocellular carcinomas (HCC) measuring >5 cm. MATERIALS AND METHODS: Between November 2013 and February 2016, 13 patients with unresectable HCC (>5 cm), ineligible for other local treatments, with a Child-Pugh score (CPS) ≤ B7, were enrolled into a single-institution phase II study. SBRT was delivered by volumetric-modulated arc radiotherapy. Radiological response was reported using modified Response Evaluation Criteria in Solid Tumours criteria and toxicities graded by Common Terminology Criteria for Adverse Events v4 criteria. RESULTS: Sixteen hepatomas (median size 7.5 cm, range 5.1-9.7 cm) were treated in 13 patients. The baseline CPS was A5/6 in nine patients (69%) and B7 in four patients (31%). Five patients (38%) received previous liver-directed treatment. The median prescribed dose was 45 Gy (range 40-45 Gy) in five fractions. The median follow-up was 17.7 months. The 1-year local control rate was 92%. The median overall survival was 17.7 months and the 1-year overall survival was 62%. The median time to local progression was not reached. Five patients (39%) had an increase in CPS by two or more points at 3 months. Overall, there were 10 grade 3 acute toxicities occurring in seven patients, of which six were haematological. Quality of life remained clinically stable or improved at 3 months in 61.5% and 53.8% of patients based on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Global Health Score and Functional Assessment of Cancer Therapy - Hepatobiliary version 4 score, respectively. CONCLUSIONS: In our cohort, SBRT to unresectable large HCC tumours provided excellent local control with acceptable toxicities. Regional recurrence remained the major cause of failure. Further studies are warranted to examine the role for SBRT in combination with other modalities to maximise disease control in the liver.

In the Era After the European Organisation for Research and Treatment of Cancer 'Boost' Study, is the Additional Radiotherapy to the Breast Tumour Bed Still Beneficial for Young Women?

AIMS: The European Organisation for Research and Treatment of Cancer (EORTC) 22,881-10,882 trial showed significant benefit of a radiotherapy boost (RTB) in women ≤40 years in a pre-hormone therapy (HT) era. We determined how the use of HT and RTB changed in response to clinical guidelines and whether the benefit of routine RTB was still observed in the HT era. MATERIALS AND METHODS: Between 1996 and 2004, a provincial database identified all women ≤40 years with breast cancer who met the inclusion criteria of the EORTC trial. In total, 411 patients were classified into three eras defined by the guidelines: era 1 (discretionary HT, discretionary RTB); era 2 (routine HT, discretionary RTB); era 3 (routine HT, routine RTB). HT use, RTB use and cumulative incidence of local recurrence were calculated and compared across eras. RESULTS: HT use increased after the first policy change from 13% to 75% for oestrogen receptor-positive patients (P < 0.01). RTB use also increased from 33% to 76% following the second policy change (P < 0.01). At 10 years, the cumulative incidence of local recurrence was 12% in era 1, 6% in era 2 and 6% in era 3 (era 2 versus era 3, P = 0.92). For patients in the routine HT era (eras 2 and 3 combined) there was no significant difference in local recurrence between RTB and 'no RTB' patients (6% versus 7%, P = 0.81). CONCLUSIONS: The routine use of HT and RTB increased significantly after new practice guidelines. Introduction of the HT guideline was associated with a 6% improvement in local recurrence at 10 years. No improvement in local recurrence was associated with the introduction of the RTB guideline in the HT era. The routine use of a boost in unselected young women with negative margins should be re-evaluated in the current HT era.

Whole Brain Radiotherapy Versus Stereotactic Radiosurgery in Poor-Prognosis Patients with One to 10 Brain Metastases: A Randomised Feasibility Study.

AIMS: A significant proportion of patients with brain metastases have a poor prognosis, with a life expectancy of 3-6 months. To determine the optimal radiotherapeutic strategy for brain metastases in this population, we conducted a randomised feasibility study of whole brain radiotherapy (WBRT) versus stereotactic radiosurgery (SRS). MATERIALS AND METHODS: Patients with a life expectancy of 3-6 months and between one and 10 brain metastases with a diameter ≤4 cm were enrolled at six Canadian cancer centres. Patients were randomly assigned (1:1) to receive either WBRT (20 Gy in five fractions) or SRS (15 Gy in one fraction). The primary end point was the rate of accrual per month. Secondary feasibility and clinical end points included the ratio of accrued subjects to screened subjects. This trial is registered with ClinicalTrials.gov (number NCT02220491). RESULTS: In total, 210 patients were screened to enrol 22 patients into the trial; 20 patients were randomised between the two arms. Two patients did not receive treatment because one patient died and another patient withdrew consent after being enrolled. Patients were accrued between January 2015 and November 2017; the accrual rate was 0.63 patients/month. The most common reasons for exclusion were anticipated median survival outside the required range (n = 40), baseline Karnofsky Performance Score below 70 (n = 28) and more than 10 brain metastases (n = 28). The median follow-up was 7.0 months and the median survival was 7.0 months for all patients in the trial. The median intracranial progression-free survival was 1.8 months in the SRS arm and 9.2 months in the WBRT arm. There were five grade 3+ toxicities in the SRS arm and one grade 3+ toxicity in the WBRT arm; no grade 5 toxicities were observed. The cumulative rates of retreatment were 40% in the SRS arm and 40% in the WBRT arm. CONCLUSIONS: A randomised trial evaluating WBRT versus SRS in patients with one to 10 metastases and a poor prognosis is feasible. A slower than expected accrual rate and difficulties with accurate prognostication were identified as issues in this feasibility study. A larger phase III randomised trial is planned to determine the optimal treatment in this patient population.

Stereotactic Body Radiotherapy for Small Unresectable Hepatocellular Carcinomas.

AIMS: Stereotactic body radiotherapy (SBRT) is an option for the treatment of hepatocellular carcinoma (HCC) in patients ineligible for standard local therapies. This study reports on the safety and efficacy of SBRT in small HCC tumours (≤5 cm) in the province of British Columbia. MATERIALS AND METHODS: Between March 2011 and July 2015, 31 patients with Child-Pugh Class A or B, with small HCCs measuring ≤5 cm were treated with SBRT at our institution. Primary end points were local control, progression-free survival, overall survival and toxicity. RESULTS: Thirty-four hepatomas (median size 3.3 cm, range 1.3-5.0 cm) were treated. The median follow-up was 18.3 months. Twenty-six patients (84%) had received previous liver-directed treatments. Most patients (88%) were treated with 45 Gy in three or five fractions. Six patients (19%) had worsened Child-Pugh score by two or more points during follow-up; overall 32% of patients experienced ≥ grade 3 + toxicities. One-year local control and overall survival were 94 and 84%, respectively. One-year progression-free survival was 49%; 81% of patients with disease progression received further HCC therapy. On univariate analysis, small tumour size predicted for improved overall survival (P = 0.01) whereas prescription biological equivalent dose (BED10) ≥100Gy10 approached significance (P = 0.06). CONCLUSION: SBRT provides high local control to small inoperable HCC. SBRT can be delivered safely even after previous liver-directed therapies and further liver therapies can follow treatment with SBRT. Although overall 32% of patients experienced ≥ grade 3 + toxicities, and 19% had a deterioration in Child-Pugh score of two or more points, these changes were mainly transient with minimal clinical impact. Despite excellent local control, disease progression outside of the irradiated site remains prominent. Further studies are warranted to examine combined therapy approaches to maximise disease control.

Decreased event-related theta power and phase-synchrony in young binge drinkers during target detection: An anatomically-constrained MEG approach.

BACKGROUND: The prevalence of binge drinking has risen in recent years. It is associated with a range of neurocognitive deficits among adolescents and young emerging adults who are especially vulnerable to alcohol use. Attention is an essential dimension of executive functioning and attentional disturbances may be associated with hazardous drinking. The aim of the study was to examine the oscillatory neural dynamics of attentional control during visual target detection in emerging young adults as a function of binge drinking. METHOD: In total, 51 first-year university students (18 ± 0.6 years) were assigned to light drinking ( n = 26), and binge drinking ( n = 25) groups based on their alcohol consumption patterns. A high-density magnetoencephalography signal was combined with structural magnetic resonance imaging in an anatomically constrained magnetoencephalography model to estimate event-related source power in a theta (4-7 Hz) frequency band. Phase-locked co-oscillations were further estimated between the principally activated regions during task performance. RESULTS: Overall, the greatest event-related theta power was elicited by targets in the right inferior frontal cortex and it correlated with performance accuracy and selective attention scores. Binge drinkers exhibited lower theta power and dysregulated oscillatory synchrony to targets in the right inferior frontal cortex, which correlated with higher levels of alcohol consumption. CONCLUSIONS: These results confirm that a highly interactive network in the right inferior frontal cortex subserves attentional control, revealing the importance of theta oscillations and neural synchrony for attentional capture and contextual maintenance. Attenuation of theta power and synchronous interactions in binge drinkers may indicate early stages of suboptimal integrative processing in young, highly functioning binge drinkers.

Non-invasive measurement of choroidal volume change and ocular rigidity through automated segmentation of high-speed OCT imaging.

We have developed a novel optical approach to determine pulsatile ocular volume changes using automated segmentation of the choroid, which, together with Dynamic Contour Tonometry (DCT) measurements of intraocular pressure (IOP), allows estimation of the ocular rigidity (OR) coefficient. Spectral Domain Optical Coherence Tomography (OCT) videos were acquired with Enhanced Depth Imaging (EDI) at 7Hz during ~50 seconds at the fundus. A novel segmentation algorithm based on graph search with an edge-probability weighting scheme was developed to measure choroidal thickness (CT) at each frame. Global ocular volume fluctuations were derived from frame-to-frame CT variations using an approximate eye model. Immediately after imaging, IOP and ocular pulse amplitude (OPA) were measured using DCT. OR was calculated from these peak pressure and volume changes. Our automated segmentation algorithm provides the first non-invasive method for determining ocular volume change due to pulsatile choroidal filling, and the estimation of the OR constant. Future applications of this method offer an important avenue to understanding the biomechanical basis of ocular pathophysiology.

Analysis of chromosome damage for biodosimetry using imaging flow cytometry.

The dicentric chromosome assay (DCA), which involves counting the frequency of dicentric chromosomes in mitotic lymphocytes and converting it to a dose-estimation for ionizing radiation exposure, is considered to be the gold standard for radiation biodosimetry. Furthermore, for emergency response, the DCA has been adapted for triage by simplifying the scoring method [1]. With the development of new technologies such as the imaging flow cytometer, it may now be possible to adapt this microscope-based method to an automated cytometry method. This technology allows the sensitivity of microscopy to be maintained while adding the increased throughput of flow cytometry. A new protocol is being developed to adapt the DCA to the imaging cytometer in order to further increase the rapid determination of a biological dose. Peripheral blood mononuclear cells (PBMC) were isolated from ex vivo irradiated whole blood samples using a density gradient separation method and cultured with PHA and Colcemid. After 48h incubation, the chromosomes were isolated, stained for DNA content with propidium iodide (PI) and labelled with a centromere marker. Stained chromosomes were then analyzed on the ImageStream(×) (EMD-Millipore, Billerica, MA). Preliminary results indicate that individual chromosomes can be identified and mono- and dicentric chromosomes can be differentiated by imaging cytometry. A dose response curve was generated using this technology. The details of the method and the dose response curve are presented and compared to traditional microscope scoring. Imaging cytometry is a new technology which enables the rapid, automated analysis of fluorescently labelled chromosomes. Adapting the dicentric assay to this technology has the potential for high throughput analysis for mass casualty events.

Vascular endothelial growth factor as capillary permeability agent in ovarian hyperstimulation syndrome.

We investigated the role of vascular endothelial growth factor (VEGF) in ovarian hyperstimulation syndrome (OHSS). Two similar peaks of permeability activity were seen in OHSS ascites and liver ascites spiked with recombinant human VEGF (rhVEGF); no activity was seen in control liver ascites. Incubation with rhVEGF antiserum decreased activity in the two OHSS peaks by 79% and 65% and the two spiked liver peaks by 49% and 50%. Control serum produced 24% and 27%, and 17% and 0% reductions, respectively. This is evidence that the major capillary permeability agent in OHSS ascites fluid is VEGF.

Immunolocalization of the cellular adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and platelet endothelial cell adhesion molecule (PECAM), in human endometrium throughout the menstrual cycle.

In the present study the presence and distribution of cellular adhesion molecules involved in leukocyte binding were investigated in human endometrium. Endometrial biopsies (n = 45) were collected from women at all stages of normal menstrual cycles. Consecutive cryostat sections of endometrium were immunostained with monoclonal antibodies to intercellular adhesion molecule-1 (ICAM-1) and platelet endothelial cell adhesion molecule (PECAM) and haematoxylin and eosin. Primary antibody binding was visualized using a streptavidin-biotin system. Strong staining for PECAM was observed in endothelial cells of all vessel types and in focal areas of stroma including single cells, small clusters and larger aggregates of cells. At menstruation, however, almost the entire stroma stained for PECAM which was temporally related to a massive influx of leukocytes. ICAM-1 staining, which was consistently less intense than PECAM staining, was detected in vascular endothelial cells during the cycle, reaching a peak at menstruation. Unlike PECAM, ICAM-1 staining did not occur consistently across all vessel types. Stromal staining for ICAM-1 was rare except at menstruation, when almost the entire stroma showed positive staining for ICAM-1. No glandular or luminal epithelial staining was detected for either PECAM or ICAM-1. This study demonstrates that PECAM and ICAM-1 are expressed on endothelial cells of veins, arterioles and capillaries, and stromal cells within human endometrium.

Reduction in endometrial neutrophils in proximity to implanting rat blastocysts.

An antiserum to rat neutrophils was raised and used to follow the distribution of endometrial neutrophils during the peri-implantation period. Uteri from four pregnant and four pseudopregnant rats killed at 14:00, 17:00, 20:30 and 23:00 h on day 5 of pregnancy and 09:00 h on day 6 were sectioned. Four sections from each of four implantation sites and four intersites from each rat were immunostained. There was wide variability among rats in the number of endometrial neutrophils, but a nested analysis of variance showed significantly fewer neutrophils at implantation sites than at intersites from 20:30 h onwards. This difference was primarily due to the presence of more neutrophils in intersite regions of the endometrium. The results from this study do not support a role for neutrophils in the implantation-associated increase in microvascular permeability or decidualization in rats.

Turner's syndrome patients lack tight junctions between uterine epithelial cells.

Eleven endometrial biopsies, taken from six Turner's syndrome patients receiving hormone replacement therapy prior to treatment by oocyte donation and embryo transfer, were assessed by freeze fracture followed by electron microscopy for epithelial tight junctions. Nine of the eleven biopsies had no discernible tight junctions; the other two biopsies had reduced and disorganized junctional structures. Two patients subsequently became pregnant following embryo transfer. It is concluded that compromised epithelial integrity does not prevent embryo implantation in the human, an observation that is consistent with a barrier role for the epithelium except at times when appropriately conditioned with oestrogen and progesterone to induce receptivity for implantation.

Tight junctions of human uterine epithelial cells change during the menstrual cycle: a morphometric study.

Tight junctions between luminal epithelial cells of the human uterus were studied by freeze-fracture electron microscopy. It was found that junctional complexity decreased during the menstrual cycle, and we explore how this finding may contribute to the role of the uterus in facilitating implantation.

Early evaluation of postmenopausal hormonal steroid therapy by scanning electron microscopy of the uterine epithelium.

Scanning electron microscopy has been used in a preliminary study to evaluate the value of steroid replacement therapies in restoring uterine epithelium in postmenopausal patients. All therapies resulted in increased epithelium over controls, but one regime was markedly better than others.

Vascular response in a non-uterine site to implantation-stage embryos following interspecies transfers between the rat, mouse, and guinea-pig.

Pre-implantation-stage embryos from rats, mice, and guinea-pigs were transferred to a non-uterine site--the anterior chamber of the eye--of female recipients. All 9 combinations of transfers were performed: 3 allogeneic (intraspecies) transfers as controls, and 6 xenogeneic (interspecies) transfers. Implantation, as judged by extravasation from blood vessels of the iris or ciliary body occurred with success rates of 90.4% per transfer in the control rat group. 76.9% in the control mouse group, and 81.8% in the control guinea-pig group. Significantly reduced implantation rates occurred in the rat to guinea-pig (0%), mouse to rat (46.9%), mouse to guinea-pig (6.7%), and guinea-pig to rat (0%) groups compared to controls. Reductions, although not significant, also occurred in the other 2 groups: rat to mouse (77.8%), and guinea-pig to mouse (44.4%). These results together with some ultrastructural and light-microscopical observations suggest a degree of species specificity involved in the vascular response to the implanting embryo. We propose that the peri-implantation embryo produces a signal(s) which is to some extent species specific and which in the normal allogeneic situation is responsible for the early vascular effects seen at implantation in most eutherian mammals.

Uterine receptivity in women receiving steroid replacement therapy for premature ovarian failure: ultrastructural and endocrinological parameters.

Endometrial biopsies and plasma oestradiol (E2) and progesterone (P4) levels in 23 patients were evaluated during 26 replacement therapy cycles for premature ovarian failure. Plasma E2 and P4 levels showed wide patient to patient variability, despite each patient being given the same hormone replacement therapy. Biopsies were studied by conventional histological dating and scanning electron microscopy (SEM). Eight morphological features of the surface epithelium that have previously been linked to uterine receptivity for implantation were identified and quantified. No correlation was found between endometrial surface morphology by SEM and circulating E2 and P4 levels. The results of this study do not support the hypothesis that there is an obligatory link between any of the eight morphological features measured in this study and uterine receptivity for implantation. To date, three ongoing pregnancies have been achieved following 18 embryo transfers to a total of 10 of the women in the study group.

Ultrastructural study of human uterine epithelium from a patient with a confirmed pregnancy.

Scanning and transmission electron microscopy have been used to study the uterine epithelial cells from a pregnant human uterus approximately 8 days after ovulation. The ultrastructural appearance of the epithelial cells generally conforms with that previously described as showing receptivity, although some significant regional variability exists.

Vascular response in a non-uterine site to implantation-stage embryos in the rat and guinea-pig: in vivo and ultrastructural studies.

Preimplantation-stage embryos were transferred to the anterior eye chamber of recipient rats and guinea-pigs. After implantation had occurred the influence of the embryo on the iris vasculature was examined ultrastructurally. In both species, the earliest effect of embryonic implantation was an increased stromal oedema. Under increasing embryonic influence the vascular endothelial cells showed an increased number of projections into the vascular lumen, while in the rat, endothelial projections were also found pushing back into the basement membrane. In the rat, the endothelium became very irregular in thickness prior to complete disintegration and loss during more advanced stages of implantation. Rat embryonic trophoblast was found invading iris vasculature, particularly in areas where the iridial endothelium was partially or completely missing. Other cells in the iris, including the stroma, appeared to be less affected. In the guinea-pig, however, trophoblast cells appeared to be capable of invading the vasculature by displacing endothelial cells that still appeared morphologically normal.

Embryo implantation in the anterior chamber of the eye. Effects on uterine allografts and the microvasculature.

A model suitable for the in vivo study of embryo implantation in the presence or absence of uterine tissue has been developed. After transplantation of a uterine allograft to the anterior chamber of rat eyes, embryos were transferred to control, normally cycling, and pseudopregnant recipients. Implantation rates were 86%, 46% and 49%, respectively, for the three groups. Despite embryo growth rates being delayed by 3-4 days, histologic studies showed relatively normal egg cylinder stage embryos equivalent to those of day 8 of normal development. Uterine allografts varied greatly in appearance, from inert-looking pieces of connective tissue to recognizable uterine structures with an epithelium and a degree of decidual response. Reduced implantation rates in the presence of a uterine allograft may be due either to the uterine production of blastotoxic substances or the presence of a chronic inflammatory reaction resulting from the rejection of the allograft by the recipient. This model provides a unique system for continuous, noninvasive in vivo observations of the implantation process.

Surface ultrastructure of uterine epithelial cells in women with premature ovarian failure following steroid hormone replacement.

Scanning electron microscopy has been used to study the apical surface of uterine epithelial cells in women with premature ovarian failure following steroid hormone replacement therapy. A variety of ultrastructural characteristics are identified which could indicate a uterus that is receptive for blastocyst implantation.