A Canadian approach to the regionalization of testis cancer: A review

At the Canadian Testis Cancer Workshop, the rationale and feasibility of regionalization of testis cancer care were discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician’s assistants, residents and fellows, and nurses, as well as patients and patient advocacy groups. This review summarizes the discussion and recommendations of one of the central topics of the workshop — the centralization of testis cancer in Canada. It was acknowledged that non-guideline-concordant care in testis cancer occurs frequently, in the range of 18–30%. The National Health Service in the U.K. stipulates various testis cancer care modalities be delivered through supra-regional network. All cases are reviewed at a multidisciplinary team meeting and aspects of care can be delivered locally through the network. In Germany, no such network exists, but an insurance-supported online second opinion network was developed that currently achieves expert case review in over 30% of cases. There are clear benefits to regionalization in terms of survival, treatment morbidity, and cost. There was agreement at the workshop that a structured pathway for diagnosis and treatment of testis cancer patients is required. Regionalization may be challenging in Canada because of geography; independent administration of healthcare by each province; physicians fearing loss of autonomy and revenue; patient unwillingness to travel long distances from home; and the inability of the larger centers to handle the ensuing increase in volume. We feel the first step is to identify the key performance indicators and quality metrics to track the quality of care received. After identifying these metrics, implementation of a “networks of excellence” model, similar to that seen in sarcoma care in Ontario, could be effective, coupled with increased use of health technology, such as virtual clinics and telemedicine

Sociodemographic and Disease Correlates of Body Image Distress among Patients with Systemic Sclerosis

Body image concerns are infrequently studied in systemic sclerosis (SSc), even though significant visible disfigurement is common. The objective of this study was to identify sociodemographic and disease-related correlates of dissatisfaction with appearance and social discomfort among people with SSc.SSc patients came from the 15-center Canadian Scleroderma Research Group Registry. Sociodemographic information was based on patient self-report. Disease characteristics were obtained via physician examinations. The Brief-SWAP was used to assess dissatisfaction with appearance and social discomfort. Structural equation models were conducted with MPlus to determine the relationship of dissatisfaction with appearance and social discomfort with age, sex, education, marital status, race/ethnicity, disease duration, skin involvement, telangiectasias, skin pigmentation changes, and hand contractures.A total of 489 SSc patients (432 female, 57 male) were included. Extent of skin involvement was significantly associated with both dissatisfaction with appearance and social discomfort (standardized regression coefficients = 0.02, p = 0.001; 0.02, p = 0.020, respectively), as was skin involvement in the face (0.18, p = 0.016; 0.23, p = 0.006, respectively). Greater social discomfort was robustly associated with younger age (-0.017, p<0.001) and upper-body telangiectasias (0.32, p = 0.021). Dissatisfaction with appearance was associated with hand contractures (0.07, p = 0.036).This study found that dissatisfaction with appearance and social discomfort were associated with numerous disfiguring characteristics of SSc, in addition to age. These results underline that there are multiple factors contributing to body image distress in SSc, as well as the need to attend to both disease and social contexts in understanding the impact of disfigurement among patients

Genome-wide linkage screen for testicular germ cell tumour susceptibility loci

A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the diseas

Genome Sequence of Fusobacterium nucleatum Subspecies Polymorphum — a Genetically Tractable Fusobacterium

Fusobacterium nucleatum is a prominent member of the oral microbiota and is a common cause of human infection. F. nucleatum includes five subspecies: polymorphum, nucleatum, vincentii, fusiforme, and animalis. F. nucleatum subsp. polymorphum ATCC 10953 has been well characterized phenotypically and, in contrast to previously sequenced strains, is amenable to gene transfer. We sequenced and annotated the 2,429,698 bp genome of F. nucleatum subsp. polymorphum ATCC 10953. Plasmid pFN3 from the strain was also sequenced and analyzed. When compared to the other two available fusobacterial genomes (F. nucleatum subsp. nucleatum, and F. nucleatum subsp. vincentii) 627 open reading frames unique to F. nucleatum subsp. polymorphum ATCC 10953 were identified. A large percentage of these mapped within one of 28 regions or islands containing five or more genes. Seventeen percent of the clustered proteins that demonstrated similarity were most similar to proteins from the clostridia, with others being most similar to proteins from other gram-positive organisms such as Bacillus and Streptococcus. A ten kilobase region homologous to the Salmonella typhimurium propanediol utilization locus was identified, as was a prophage and integrated conjugal plasmid. The genome contains five composite ribozyme/transposons, similar to the CdISt IStrons described in Clostridium difficile. IStrons are not present in the other fusobacterial genomes. These findings indicate that F. nucleatum subsp. polymorphum is proficient at horizontal gene transfer and that exchange with the Firmicutes, particularly the Clostridia, is common

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome

The critical role of the linear plasmid lp36 in the infectious cycle of Borrelia burgdorferi

Borrelia burgdorferi, the aetiological agent of Lyme disease, follows a life cycle that involves passage between the tick vector and the mammalian host. To investigate the role of the 36 kb linear plasmid, lp36 (also designated the B. burgdorferi K plasmid), in the infectious cycle of B. burgdorferi, we examined a clone lacking this plasmid, but containing all other plasmids known to be required for infectivity. Our results indicated that lp36 was not required for spirochete survival in the tick, but the clone lacking lp36 demonstrated low infectivity in the mammal. Restoration of lp36 to the mutant strain confirmed that the infectivity defect was due to loss of lp36. Moreover, spirochetes lacking lp36 exhibited a nearly 4-log increase in ID50 relative to the isogenic lp36+ clone. The infectivity defect of lp36-minus spirochetes was localized, in part, to loss of the bbk17 (adeC) gene, which encodes an adenine deaminase. This work establishes a vital role for lp36 in the infectious cycle of B. burgdorferi and identifies the bbk17 gene as a component of this plasmid that contributes to mammalian infectivity

Towards an understanding of molecule capture by the antennae of male beetles belonging to the Genus <i>Rhipicera</i> (Coleoptera, Rhipiceridae)

Working on the hypothesis that an important function of the lamellate antennae of adult male beetles belonging to the genus Rhipicera is to detect scent associated with female conspecifics, and using field observations, anatomical models derived from X-ray microcomputed tomography, and scanning electron microscopy, we have investigated the behavioral, morphological, and morphometric factors that may influence molecule capture by these antennae. We found that male beetles fly upwind in a zigzag manner, or face upwind when perching, behavior consistent with an animal that is tracking scent. Furthermore, the ultrastructure of the male and female antennae, like their gross morphology, is sexually dimorphic, with male antennae possessing many more of a particular type of receptor-the sensillum placodeum-than their female counterparts (approximately 30,000 vs. 100 per antenna, respectively). Based on this disparity, we assume that the sensilla placodea on the male antennae are responsible for detecting scent associated with female Rhipicera beetles. Molecule capture by male antennae in their alert, fanned states is likely to be favoured by: (a) male beetles adopting prominent, upright positions on high points when searching for scent; (b) the partitioning of antennae into many small segments; (c) antennal morphometry (height, width, outline area, total surface area, leakiness, and narrow channels); (d) the location of the sensilla placodea where they are most likely to encounter odorant molecules; and (e) well dispersed sensilla placodea. The molecule-capturing ability of male Rhipicera antennae may be similar to that of the pectinate antennae of certain male moths.</p