Hydrogel oxygen reservoirs increase functional integration of neural stem cell grafts by meeting metabolic demands.

Injectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell survival, differentiation, and functional integration owing to the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. We show that this hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. We find that the addition of myoglobin to the hydrogel results in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. This approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.

Minimal invasiveness in soft tissue augmentation at dental implants: A systematic review and meta-analysis of patient-reported outcome measures.

The aim of this study was to compare patient-reported outcome measures (PROMs) of soft tissue substitutes versus autogenous grafts for soft tissue augmentation procedures at implant sites. Comprehensive and systematic literature searches were performed until December 2021. A focused question was formulated based on the Population, Intervention, Comparison and Outcome criteria (PICO): In patients with dental implants undergoing soft tissue augmentation (P), do soft tissue substitutes (I) compared to autogenous soft tissue graft (SCTG [subepithelial connective tissue graft]) (C) limit the post-operative morbidity and other patient reported-outcomes measures (O). Randomized controlled clinical trials, prospective-, retrospective- and case-series studies were included. Meta-analyses were performed whenever possible and the results were expressed as weighted mean differences (WMD). A total of 29 clinical studies were included. For mucosal thickness gain, soft tissue substitutes significantly reduced the pain perception compared to SCTG (n = 4; WMD = 14.91 Visual Analog Scale [VAS] units; 95% confidence interval [CI] 6.42-23.40; P < .0006) based on a 0-100 VAS scale. Based on a 0-10 VAS scale, a borderline significance of pain reduction was found when soft tissue substitutes were applied (n = 4; WMD = 1.62 VAS units; 95% CI 0.01-3.23; P = .05). For keratinized tissue gain, soft tissue substitutes significantly reduced the pain perception after keratinized tissue augmentation compared to SCTG based on a 0-100 VAS scale (n = 2; WMD = 21.43 VAS units; 95% CI 12.58-30.28; P < .0001). Based on the 0-10 VAS scale, soft tissue substitutes significantly reduced the pain as compared to SCTG (n = 4; WMD = 1.65 VAS units; 95% CI 0.66-2.64; P = .001). Regarding pain medication, soft tissue substitutes required less painkillers (n = 6; WMD = 1.56 tablets; 95% CI 1.22-1.91; P < .00001) after soft tissue augmentation. The surgery time was significantly reduced when soft tissue substitutes were used (n = 5; WMD = 10.9 minutes; 95% CI 4.60-17.19; P < .00001). There were no significant differences in satisfaction, aesthetics, and quality of life (OHIP-14) between soft tissue substitutes and autogenous grafts following soft tissue augmentation at implants sites. Soft tissue substitutes, compared to autogenous grafts, significantly improve PROMs following soft tissue augmentation at implant sites. Soft tissue substitutes can reduce pain perception, amounts of painkillers and surgery time while achieving similar levels of patient´s satisfaction as autogenous grafts without impairing the clinical outcomes. The current evidence indicates that they constitute a valid and reliable alternative to minimize the invasiveness in soft tissue augmentation procedures at implant sites.

Soft tissue augmentation with a volume-stable collagen matrix or an autogenous connective tissue graft at implant sites: Five-year results of a randomized controlled trial post implant loading.

BACKGROUND: Interventions to augment the mucosal thickness around dental implants are indicated to optimize esthetics and maintain peri-implant health. However, there is a lack of clinical data on the long-term performance of soft tissue substitutes, such as volume-stable collagen matrix (VCMX), compared to autogenous grafts, such as subepithelial connective tissue grafts (SCTGs). This randomized controlled trial aimed to assess 5-year data on clinical and radiographic outcomes at implant sites previously augmented with VCMX or SCTG. METHODS: Twenty patients were randomly assigned for soft tissue augmentation with VCMX or SCTG at single implant sites. Following abutment connection, final restorations were inserted (baseline; BL) and patients were reexamined up to 5 years (FU-5). Measurements included clinical data, marginal bone levels, mucosal thickness, and ridge contour changes. Nonparametric tests and estimates were applied for the statistical analysis. RESULTS: The median buccal mucosal thickness increased by 0.3 mm (Q1: -0.8; Q3: 1.0) in the VCMX group (P = 0.656) and 0.3 mm (Q1: 0.0; Q3: 1.0) in the SCTG group (P = 0.188) between BL and FU-5 (intergroup P = 0.752), while the ridge contour decreased by a median of -0.3 mm (-0.9; -0.1) (P = 0.078) for VCMX and -0.3 mm (-0.4; -0.2) (P = 0.039) for SCTG (intergroup P = 0.817). Peri-implant health was maintained in both groups with stable clinical and radiographic outcomes and without significant differences between the treatments. CONCLUSION: Despite the limited power and considerable dropout rate in the present study, soft tissue augmentation at implant sites with either VCMX or SCTG resulted in similar stable peri-implant tissues, favorable esthetics, and clinically negligible contour changes at 5 years post loading.

Interproximal contact loss at implant sites: a retrospective clinical study with a 10-year follow-up.

AIM: To assess the frequency and quantity of interproximal contact loss (ICL) between implant restorations and adjacent teeth after at least 10 years of follow-up (FU). METHODS: Thirty-nine patients (median age 57.3 years) with 80 implants were re-examined at least 10 years after insertion of final restorations (single crowns or fixed dental prostheses (FDPs)). Baseline (insertion of the restorations) and FU examinations encompassed the following: Stone casts were scanned and superimposed for metric assessment of tooth movements, radiographs, and clinical measurements. Outcome measures at implant sites were as follows: the extent of tooth movement and the frequency of interproximal contact loss [ICL], peri-implant marginal bone levels [MBLs], and clinical measurements (plaque control record [PCR], Bleeding on Probing [BOP], and probing depth [PD]). Data were analyzed statistically with generalized regression modeling with robust standard errors to account for within-patient clustering at 5%. RESULTS: Interproximal contact loss for at least one contact point after 10 years was observed in 50% of all implants (with open interproximal spaces up to 1.64 mm). Mesial contact points were significantly more prone to ICL than distal ones (relative risk [RR] = 1.79; 95% confidence interval [CI] = 1.07-2.99; p = .03). The type of restoration had a significant effect on ICL, with FDPs of 2 implants being significantly more prone to mesial ICL than single crowns (RR = 1.52; 95% CI = 1.02-2.25; p = .04). ICL was also associated with a significant increase in PD (+0.46 mm (95% CI = 0.04-0.88 mm; p = .03)) compared to implant sites without ICL. BOP, MBLs, and PCR were not significantly influenced by ICL. CONCLUSION: Interproximal contact loss was a common finding in 50% of the implant sites and was significantly associated with an increase in PD.

Partial pulpotomy without age restriction: a retrospective assessment of permanent teeth with carious pulp exposure.

OBJECTIVES: This study aimed to retrospectively evaluate clinical and radiographic outcomes of partial pulpotomy performed in permanent teeth with carious pulp exposure. MATERIALS AND METHODS: Records of patients undergoing treatment at an undergraduate dental clinic between 2010 and 2019 were screened for partial pulpotomies in teeth with a presumptive diagnosis of normal pulp or reversible pulpitis. The follow-up had to be ≥ 1 year. Patient data were retrieved and analyzed using Mantel-Cox chi square tests and Kaplan-Meier statistics. The level of significance was set at α = 0.05. RESULTS: Partial pulpotomy was performed in 111 cases, of which 64 (58%) fulfilled the eligibility criteria. At the time of partial pulpotomy, the mean age was 37.3 (± 13.5) years (age range 18-85). The mean observation period was 3.1 (± 2.0) years. Two early failures (3.1%) and five late failures (7.7%) were recorded. The overall success rate of maintaining pulp vitality was 89.1%, with 98.4% tooth survival. The cumulative pulp survival rates of partial pulpotomy in patients aged < 30 years, between 30 and 40 years, and > 40 years were 100%, 75.5%, and 90.5%, respectively, with no significant difference between the age groups (p = 0.225). At follow-up, narrowing of the pulp canal space and tooth discoloration were observed in 10.9% and 3.1% of cases, respectively. CONCLUSIONS: Across age groups, partial pulpotomy achieved favorable short and medium-term outcomes in teeth with carious pulp exposure. CLINICAL RELEVANCE: Adequate case selection provided, partial pulpotomy is a viable operative approach to treat permanent teeth with deep carious lesions irrespective of patients' age.

First experiences with 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancer.

BACKGROUND: Advanced salivary gland cancers become difficult to treat when they are technically irresectable and radiotherapy limits are exceeded. There is also an unmet need to improve palliative systemic therapy. Salivary glands depict the Prostate-Specific Membrane Antigen (PSMA) on 68Ga-PSMA-PET/CT, a transmembrane protein that is targeted for diagnosis and treatment of advanced prostate cancer. Some salivary gland carcinomas also express PSMA. METHODS: This study aimed to retrospectively evaluate the effectiveness of 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancers, as a last resort treatment. Patients with serious tumour-related discomfort for whom no regular option was available were selected and critically re-assessed by the tumour board. Radionuclide therapy eligibility was confirmed when tumour targeting was greater than liver SUVmax on 68Ga-PSMA-PET/CT. The protocol aimed at four cycles of 6.0-7.4 GBq 177Lu-PSMA-617 every 6-8 weeks. Clinical response was evaluated by questionnaires and radiological response by 68Ga-PSMA-PET/CT. RESULTS: Six patients were treated with 177Lu-PSMA: four adenoid cystic carcinomas, one adenocarcinoma NOS and one acinic cell carcinoma. In two patients, radiological response was observed, showing either stable disease or a partial response, and four patients reported immediate relief of tumour-related symptoms. Most reported side effects were grade 1-2 fatigue, nausea, bone pain and xerostomia. Four patients prematurely discontinued therapy: three due to disease progression and one due to demotivating (grade 1) side-effects. CONCLUSIONS: Palliative 177Lu-PSMA therapy for salivary gland cancer may lead to rapid relief of tumour-associated discomfort and may even induce disease stabilization. It is safe, relatively well tolerated and can be considered when regular treatment options fail.

The tubarial salivary glands: A potential new organ at risk for radiotherapy.

INTRODUCTION: The presence of previously unnoticed bilateral macroscopic salivary gland locations in the human nasopharynx was suspected after visualization by positron emission tomography/computed tomography with prostate-specific membrane antigen ligands (PSMA PET/CT). We aimed to elucidate the characteristics of this unknown entity and its potential clinical implications for radiotherapy. MATERIALS AND METHODS: The presence and configuration of the PSMA-positive area was evaluated in a retrospective cohort of consecutively scanned patients with prostate or urethral gland cancer (n = 100). Morphological and histological characteristics were assessed in a human cadaver study (n = 2). The effect of radiotherapy (RT) on salivation and swallowing was retrospectively investigated using prospectively collected clinical data from a cohort of head-neck cancer patients (n = 723). With multivariable logistic regression analysis, the association between radiotherapy (RT) dose and xerostomia or dysphagia was evaluated. RESULTS: All 100 patients demonstrated a demarcated bilateral PSMA-positive area (average length 4 cm). Histology and 3D reconstruction confirmed the presence of PSMA-expressing, predominantly mucous glands with multiple draining ducts, predominantly near the torus tubarius. In the head-neck cancer patients, the mean RT dose to the gland area was significantly associated with physician-rated post-treatment xerostomia and dysphagia ≥ grade 2 at 12 months (0.019/gy, 95%CI 0.005-0.033, p = .007; 0.016/gy, 95%CI 0.001-0.031, p = .036). Follow-up at 24 months had similar results. CONCLUSION: The human body contains a pair of previously overlooked and clinically relevant macroscopic salivary gland locations, for which we propose the name tubarial glands. Sparing these glands in patients receiving RT may provide an opportunity to improve their quality of life.

Assessment of tumour depth in early tongue cancer: Accuracy of MRI and intraoral ultrasound.

OBJECTIVES: Complete resection of tongue cancer is necessary to achieve local control. Unfortunately, deep resection margins are frequently inadequate. To improve deep margin control, accurate knowledge of tumour thickness is pivotal. Magnetic resonance imaging (MRI) and intraoral ultrasound (ioUS) are frequently applied for tumour staging. This study explores the accuracy of these techniques to estimate depth of invasion. MATERIALS AND METHODS: The data of patients with a T1-2 tongue cancer that had been treated surgically between 2014 and 2018 were retrospectively analysed. Measurements that had been taken by either MRI or ioUS were compared with those taken during histopathology. RESULTS: A total of 83 patients with tongue cancer had undergone a pre-operative MRI and 107 had been studied through an ioUS. Tumour thickness measured by MRI (r = 0.72) and ioUS (r = 0.78) correlated significantly (p < 0.001) with histopathological depth of invasion (DOI). In tumours with a DOI of 0-10 mm, MRI has a mean absolute difference with histopathology of 3.1 mm (SD 3.2 mm) and ioUS of 1.6 mm (SD 1.3 mm). In tumours with a DOI greater than 10 mm, MRI has a mean absolute difference of 3.5 mm (SD 3.0 mm) and ioUS of 4.7 mm (SD 3.5 mm). CONCLUSION: Estimation of histopathological DOI in tongue cancers with DOI till 10 mm is very accurate through use of ioUS. ioUS tends to underestimate DOI in tumors exceeding 10 mm DOI. MRI tends to overestimate DOI in both thin and thick tumours. Since ultrasound measurements can be performed during surgery, ioUS could potentially guide the surgeon in the achievement of adequate resection margins.

Prostate-specific membrane antigen (PSMA) expression in adenoid cystic carcinoma of the head and neck.

BACKGROUND: Treatment options for advanced head and neck adenoid cystic carcinoma (AdCC) are limited. Prostate-Specific Membrane Antigen (PSMA), a transmembrane protein that is known for its use in diagnostics and targeted therapy in prostate cancer, is also expressed by AdCC. This study aimed to analyse PSMA expression in a large cohort of primary, recurrent and metastasized AdCC of the head and neck. METHODS: One hundred ten consecutive patients with histologically confirmed AdCC in the period 1990-2017 were included. An analysis was made of clinical details, revised pathology and semiquantitative immunohistochemical expression of PSMA on tissue microarray and whole slides. Associations of PSMA expression with clinicopathological parameters were explored and survival was analysed by multivariate Cox-proportional Hazard analysis. RESULTS: PSMA expression was present in 94% of the 110 primary tumours, with a median of 31% positive cells (IQR 15-60%). Primary tumours (n = 18) that recurred (n = 15) and/or had metastases (n = 10) demonstrated 40, 60 and 23% expression respectively. Expression was not independently related to increased pathological stage, tumour grade, and the occurrence of locoregional recurrence or metastasis. After dichotomization, only primary tumour PSMA expression ≤10% appeared to be associated with reduced 10-years recurrence-free survival (HR 3.0, 95% CI 1.1-8.5, p = .04). CONCLUSIONS: PSMA is highly expressed in primary, recurrent and metastatic AdCC of the salivary and seromucous glands. PSMA expression has no value in predicting clinical behaviour of AdCC although low expression may indicate a reduced recurrence-free survival. This study provides supporting results to consider using PSMA as target for imaging and therapy when other diagnostic and palliative treatment options fail.

Randomized controlled clinical trial comparing implant sites augmented with a volume-stable collagen matrix or an autogenous connective tissue graft: 3-year data after insertion of reconstructions.

AIM: To assess mid-term clinical, radiographic and profilometric outcomes at implant sites, previously grafted with a volume-stable collagen matrix (VCMX) or an autogenous subepithelial connective tissue graft (SCTG). METHODS: VCMX or SCTG were randomly applied to single implant sites in 20 patients. Following abutment connection and insertion of final reconstructions (baseline), patients were re-examined at 6 months (6M), at 1 year (FU-1) and at 3 years (FU-3). Measurements included the following: clinical data, radiographic measurement of first bone to implant contact (fBIC), soft tissue thickness and volumetric outcomes. Non-parametric tests and estimates were applied for the statistical analysis. RESULTS: The median buccal mucosal thickness increased by 0.5 mm (Q1: -0.5; Q3: 1.25) (VCMX) (p = .281) and by 0.8 mm (Q1: 0.0; Q3: 2.5) (SCTG) (p = .047) between BL and FU-3 (intergroup p = .303). The profilometric changes of the buccal soft tissues demonstrated a median decrease between BL and FU-3 of -0.2 mm (Q1: -0.5; Q3: -0.1) (p = .039) for VCMX and a decrease of -0.1 mm (Q1: -0.8; Q3: 0.1) (p = .020) for SCTG, respectively (intergroup p = .596). Peri-implant soft tissues and bone levels remained healthy throughout the entire study period. PROMs did not show any significant differences between the groups nor significant changes over time. CONCLUSION: Minimal changes of the peri-implant tissue contour as well as of the soft tissue thickness were observed at implant sites previously grafted with VCMX or SCTG.

High CXCR4 expression in adenoid cystic carcinoma of the head and neck is associated with increased risk of locoregional recurrence.

AIM: Treatment options for head and neck adenoid cystic carcinoma (AdCC) are limited in advanced disease. Chemokine receptor type 4 (CXCR4) is present in various tumour types, including AdCC. Upregulation is associated with tumour recurrence and metastasis. New CXCR4-specific diagnostic and therapeutic target agents have recently been available. This study aimed to analyse CXCR4 expression in a cohort of primary head and neck AdCC. METHODS: After histopathological revision, tumour tissues of 73 consecutive patients with AdCC over 1990-2016 were sampled on a tissue microarray. Slides were immunohistochemically stained for CXCR4 and semiquantitatively scored. Associations between protein expression and cliniopathological parameters were tested. HRs were calculated using a Cox proportional hazard model. RESULTS: Sixty-six tumours could be analysed. CXCR4 expression was present in 81% of the tumours with a median of 29% (IQR 1-70) positive cells. Expression was univariately correlated to perineural growth (Spearman ρ .26, p=0.04) and bone invasion (Spearman ρ .32, p=0.01), but not with tumour grade.CXCR4 expression in the primary tumour was significantly higher in tumours that recurred as compared with those that did not recur (median 60%, IQR 33-72 vs 12%, IQR 1-70, Kruskal-Wallis p=0.01). After dichotomisation, >25% of CXCR4 expressions proved an independent prognosticator for a reduced recurrence-free survival (RFS) (HR 7.2, 95% CI 1.5 to 72.4, p=0.04). CONCLUSION: CXCR4 is expressed in the majority of primary AdCCs and independently correlated to worse RFS, suggesting CXCR4 as a target for imaging and therapy purposes in patients with advanced AdCC.

[Tooth Loss in Modern Dentistry]. / Zahnverlust in der modernen Zahnmedizin ­ was jetzt?

Tooth Loss in Modern Dentistry Abstract. The Swiss population follows the trend of other industrialized countries and shows an increased life expectancy compared to previous generations. Old age is reached increasingly with one's own teeth. Older restorations of teeth must be replaced and produced anew. Previous reconstructions often have the disadvantage that they are invasive and reinterventions or new fabrications are only possible to a limited extent. Advances in material technology allow new minimally invasive therapies. Adhesive bridges have become possible due to material developments in material science and allow aesthetic, non-invasive, long-term stable solutions. The specialist dentist SSO for Reconstructive Dentistry is the expert for the rehabilitation of teeth after tooth loss. He takes care of the careful restoration of the teeth according to functional and aesthetic criteria and draws on a sound knowledge of therapy options, techniques and materials acquired in many years of additional training.

Physiologic distribution of PSMA-ligand in salivary glands and seromucous glands of the head and neck on PET/CT.

OBJECTIVES: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is used for detection and (re)staging of prostate cancer. However, healthy salivary, seromucous, and lacrimal glands also have high PSMA-ligand uptake. This study aimed to describe physiologic PSMA-ligand uptake distribution characteristics in the head and neck to aid in PSMA PET/CT interpretation and to identify possible new clinical applications for PSMA-ligand imaging. STUDY DESIGN: Thirty consecutive patients who underwent PSMA PET/CT for prostate cancer were evaluated. Tracer maximum standardized uptake values (SUVmax) in the salivary, seromucous, and lacrimal glands were determined visually and quantitatively. Overall and intraindividual variations were reported. RESULTS: All gland locations had increased tracer uptake. The mean SUVmax ± standard deviation varied: parotid 12.3 ± 3.9; submandibular 11.7 ± 3.5; sublingual 4.5 ± 1.9; soft palate 2.4 ± 0.5; pharyngeal wall 4.3 ± 1.3; nasal mucosa 3.4 ± 0.9; supraglottic larynx 2.7 ± 0.7; and lacrimal 6.2 ± 2.2. The parotid had the largest overall variation in SUVmax (5.2-22.9), and the sublingual glands had the largest mean intraindividual difference (18.1%). CONCLUSIONS: Major and minor salivary and seromucous glands consistently have high PSMA-ligand uptake. Minor gland locations can be selectively visualized by this technique for the first time. This provides potential new applications such as quantification of present salivary gland tissues and individualization of radiotherapy for head and neck cancer or lutetium-177-PSMA radionuclide treatment.

Intraoral ultrasonography to measure tumor thickness of oral cancer: A systematic review and meta-analysis.

Early oral cancer is preferably treated by surgery. Its complete removal is essential for locoregional control and disease-free survival. Inadequate resection margins require adjuvant therapy such as re-resection or (chemo)radiation, that causes extra morbidity and oral discomfort. Intraoral ultrasonography (US) is reported to be of value in determining tumor thickness. Intraoperative visualization of the tumor may facilitate the resection and ensure adequate surgical margins. Furthermore, accurate prediction of tumor thickness could help determine the treatment strategy of the clinically node-negative neck, as thickness and depth of invasion are predictors of cervical metastasis as well as prognosticators of survival. The 8th edition of the American Joint Committee on Cancer staging system for oral squamous cell carcinoma has included depth of invasion as parameter for cT-stage. The aim of this review is to analyze the accuracy of intraoral US in determining tumor thickness in oral cancer. A systematic search was conducted, and the quality of the included papers was assessed using the QUADAS-2 tool for diagnostic accuracy studies. Subsequently, a meta-analysis was performed on the available individual participant data of 240 patients. Most of the twelve included studies focused on T1-2 tongue cancer (n = 129). Meta-analysis showed a high correlation in tumor thickness within this subgroup as measured by intraoral US and histopathology (r = 0.82, p < .001), with minor overestimation of 0.5 mm on US. It is concluded that intraoral US is very accurate in determining tumor thickness in early oral tongue cancer.

Prostate-specific membrane antigen PET imaging and immunohistochemistry in adenoid cystic carcinoma-a preliminary analysis.

BACKGROUND: Adenoid cystic carcinoma (AdCC) of the head and neck is an uncommon malignant epithelial tumour of the secretory glands. Many patients develop slowly growing local recurrence and/or distant metastasis, for which treatment options are limited. A retrospective analysis of 9 AdCC patients was conducted to analyse the visualization of AdCC on PSMA PET/CT and to investigate the expression of PSMA on primary, recurrent and metastatic AdCC tumour tissue using immunohistochemistry. RESULTS: Local recurrence occurred in six patients and eight developed distant metastasis. All PET/CTs depicted PSMA-ligand uptake. Four PSMA PET/CTs showed suspected residual disease, eight scans depicted uptake in areas suspected of distant metastasis. Median Maximum Standardized Uptake Value (SUVmax) in local recurrent and distant metastatic AdCC was 2.52 (IQR 2.41-5.95) and 4.01 (IQR 2.66-8.71), respectively. All primary tumours showed PSMA expression on immunohistochemistry (5-90% expression), as well as all available specimens of local recurrence and distant metastases. CONCLUSION: PSMA PET/CT is able to detect and visualize local recurrent and distant metastatic AdCC. PSMA-specific targeting is supported by PSMA expression on immunohistochemistry.

Recent advances in colonoscopy.

Colonoscopy is an important and frequently performed procedure. It is effective in the prevention of colorectal cancer and is an important test in the investigation of many gastrointestinal symptoms. This review focuses on developments over the last 5 years that have led to changes in aspects of colonoscopy, including patient preparation, technical factors, therapeutic procedures, safety, and quality.

Genes located in a chromosomal inversion are correlated with territorial song in white-throated sparrows.

The genome of the white-throated sparrow (Zonotrichia albicollis) contains an inversion polymorphism on chromosome 2 that is linked to predictable variation in a suite of phenotypic traits including plumage color, aggression and parental behavior. Differences in gene expression between the two color morphs, which represent the two common inversion genotypes (ZAL2/ZAL2 and ZAL2/ZAL2(m) ), may therefore advance our understanding of the molecular underpinnings of these phenotypes. To identify genes that are differentially expressed between the two morphs and correlated with behavior, we quantified gene expression and terrirorial aggression, including song, in a population of free-living white-throated sparrows. We analyzed gene expression in two brain regions, the medial amygdala (MeA) and hypothalamus. Both regions are part of a 'social behavior network', which is rich in steroid hormone receptors and previously linked with territorial behavior. Using weighted gene co-expression network analyses, we identified modules of genes that were correlated with both morph and singing behavior. The majority of these genes were located within the inversion, showing the profound effect of the inversion on the expression of genes captured by the rearrangement. These modules were enriched with genes related to retinoic acid signaling and basic cellular functioning. In the MeA, the most prominent pathways were those related to steroid hormone receptor activity. Within these pathways, the only gene encoding such a receptor was ESR1 (estrogen receptor 1), a gene previously shown to predict song rate in this species. The set of candidate genes we identified may mediate the effects of a chromosomal inversion on territorial behavior.

Importance of dispersal routes that minimize open-ocean movement to the genetic structure of island populations.

Islands present a unique scenario in conservation biology, offering refuge yet imposing limitations on insular populations. The Kimberley region of northwestern Australia has more than 2500 islands that have recently come into focus as substantial conservation resources. It is therefore of great interest for managers to understand the driving forces of genetic structure of species within these island archipelagos. We used the ubiquitous bar-shouldered skink (Ctenotus inornatus) as a model species to represent the influence of landscape factors on genetic structure across the Kimberley islands. On 41 islands and 4 mainland locations in a remote area of Australia, we genotyped individuals across 18 nuclear (microsatellite) markers. Measures of genetic differentiation and diversity were used in two complementary analyses. We used circuit theory and Mantel tests to examine the influence of the landscape matrix on population connectivity and linear regression and model selection based on Akaike's information criterion to investigate landscape controls on genetic diversity. Genetic differentiation between islands was best predicted with circuit-theory models that accounted for the large difference in resistance to dispersal between land and ocean. In contrast, straight-line distances were unrelated to either resistance distances or genetic differentiation. Instead, connectivity was determined by island-hopping routes that allow organisms to minimize the distance of difficult ocean passages. Island populations of C. inornatus retained varying degrees of genetic diversity (NA = 1.83 - 7.39), but it was greatest on islands closer to the mainland, in terms of resistance-distance units. In contrast, genetic diversity was unrelated to island size. Our results highlight the potential for islands to contribute to both theoretical and applied conservation, provide strong evidence of the driving forces of population structure within undisturbed landscapes, and identify the islands most valuable for conservation based on their contributions to gene flow and genetic diversity.

Non-neoplastic findings at colonoscopy after positive faecal occult blood testing: data from the English Bowel Cancer Screening Programme.

BACKGROUND: The aim of the English Bowel Cancer Screening Programme (BCSP) is to diagnose early colorectal cancer and advanced adenomas. However, other findings are also reported at screening colonoscopy. Small studies demonstrate findings other than cancer or adenomas (non-neoplastic findings (NNF)) in 11-25%. OBJECTIVES AND SETTING: Describe the frequency and nature of NNF within the BSCP. METHODS: Data were obtained from the BCSP national database for all individuals undergoing colonoscopic investigation after positive faecal occult blood testing between August 2006 and November 2011. Data included demographics, smoking status, neoplastic findings and NNF. RESULTS: 121728 colonoscopies were analysed. ≥1 NNF were found in 26251 cases (21.6%). Diverticular disease (18875 cases) and haemorrhoids (7011) were the most frequently reported. Inflammatory bowel disease (IBD) was reported in 2152 cases. Individuals with a neoplastic diagnosis were less likely to have an NNF than those without (19.8% v 24.4%, p < 0.001). After adjustment for confounding using multivariable analysis, older age was still associated with a small but statistically significant risk of NNF. CONCLUSIONS: The BCSP generates a significant volume of NNF. A small proportion of individuals were found to have inflammatory bowel disease (IBD) - an important diagnosis with implications for long-term management. BCSP participants should be aware that findings other than neoplasia may be detected and the relevance of these findings to that individual is not known. Reporting of NNF varies between colonoscopists, and potential underreporting is a limitation of this study. Further study is required to establish the impact of NNF on primary and secondary care.