Family history in the Finnish Prostate Cancer Screening Trial

Family history (FH) is one of the few known risk factors for prostate cancer (PC). There is also new evidence about mortality reduction in screening of PC with prostate‐specific antigen (PSA). Therefore, we conducted a prospective study in the Finnish Prostate Cancer Screening Trial to evaluate the impact of FH on outcomes of PC screening. Of the 80,144 men enrolled, 31,866 men were randomized to the screening arm and were invited for screening with PSA test (cut‐off 4 ng/ml) every 4 years. At the time of each invitation, FH of PC (FH) was assessed through a questionnaire. The analysis covered a follow‐up of 12 years from randomization for all men with data on FH. Of the 23,702 (74.3%) invited men attending screening, 22,756 (96.0%) provided information of their FH. Altogether 1,723 (7.3%) men reported at least one first‐degree relative diagnosed with PC and of them 235 (13.6%) were diagnosed with PC. Men with a first‐degree FH had increased risk for PC (risk ratio (RR) 1.31, p < 0.001) and the risk was especially elevated for interval cancer (RR 1.65, 95% CI 1.27–2.15). Risk for low‐grade (Gleason 2–6) tumors was increased (RR 1.46, 95% CI 1.15–1.69), but it was decreased for Gleason 8–10 tumors (RR 0.48, 95% CI 0.25–0.95). PSA test performance (sensitivity and specificity) was slightly inferior for FH positives. No difference in PC mortality was observed in terms of FH. Our findings provide no support for selective PSA screening targeting men with FH of PC.     

Erratum to: Long-term results of surgery for lumbar spinal stenosis: a randomised controlled trial

European Spine Journal -     

Factors related to frequency,type, and outcome of anal fistulas in Crohn's disease

PURPOSE: Relation of clinical factors to frequency, type, and, in particular, outcome of anal fistulas in Crohn's disease was studied. METHODS: One hundred twelve patients seen in this hospital between January 1972 and June 1993 who suffered from Crohn's disease were included in the study. Those 35 (31 percent) with anal fistulas were reexamined or interviewed and asked about their perianal symptoms and anal control. RESULTS: Rectal involvement of Crohn's disease was associated with an increased incidence of anal fistula (49 vs. 17 percent;P <0.01), especially high ones (82 vs. 17 percent;P <0.01). Ten of 18 patients with low fistulas underwent fistulotomy; all 10 fistulas healed, but slowly (mean healing time, 7.5 months), and 4 of them recurred. Of eight low fistulas managed by drainage alone, four healed. Finally, 11 of 18 patients with low fistulas had their fistulas healed. Fourteen of 17 patients with high fistulas were primarily treated by drainage and 3 by local surgery. Finally, only three patients had healed fistulas—two after simple drainage and one after local surgery, and seven patients had to undergo proctectomy. Only two patients with low fistulas required proctectomy. Eight patients (33 percent) of those 24 with fistulas in whom anal continence could be assessed, 5 with local surgery and 3 with drainage alone, reported minor defects in anal control. CONCLUSIONS: Fistulotomy is a justifiable option with satisfactory results for low symptomatic anal fistulas associated with Crohn's disease, although healing may be delayed and some fistulas will recur. Outcome of high fistulas is less satisfactory, and proctectomy is ultimately required in a number of patients; therefore, for high fistulas a conservative approach is primarily recommended.     

Identification and characterization of melanocortin-4 receptor gene mutations in morbidly obese finnish children and adults

Two Finnish cohorts, comprising 56 children with severe early-onset obesity (relative weight for height greater than or equal to +70% before age 10) and 252 morbidly obese adults (body mass index, > or = 40 kg/m(2)), were screened for melanocortin-4 receptor (MC4R) mutations. We identified a pathogenic mutation (S127L) in one child, causing severe early-onset obesity. We describe the phenotype of this particular mutation for the first time. We also identified a novel (I226T) polymorphism in the coding and two new variations (-439delGC and 1059C>T) outside the coding region of the MC4R gene. Three previously described polymorphisms (V103I, T112M, and I125L) were identified. In vitro functional studies of variants T112M, S127L, and I226T supported a pathogenic role of the S127L mutation, because signaling properties of the receptor in response to the MC4R agonists alpha-MSH, beta-MSH, and gamma(1)-MSH were impaired. The S127L mutation did not affect receptor inhibition by the antagonist agouti-related protein. Localization of the three variant receptors was similar to that of wild type. In conclusion, a pathogenic MC4R mutation was found among subjects with severe early-onset obesity but not among morbidly obese adults. Impaired function of the S127L receptor was due to reduced activation, not a defect of protein transport to the cell membrane.     

Human herpesvirus-6 infection is associated with adhesion molecule induction and lymphocyte infiltration in liver allografts

BACKGROUND/AIMS: Human herpesvirus-6 (HHV-6) infection has been recently described in liver transplants. HHV-6 may infect the transplant and cause graft dysfunction. Some association between HHV-6 and rejection has also been recorded. We have now investigated the possible involvement of HHV-6 in the intragraft immunological processes, adhesion molecules induction and lymphocyte activation. METHODS: HHV-6 was detected in liver biopsies of 19 patients transplanted in the period from 1996 to 2000. Patients with other infections or rejection were excluded from the study. Finally, 19 biopsies of eight allografts with pure HHV-6 infection were available. Adhesion molecules (ICAM-1, VCAM-1, ELAM-1) and their ligands (LFA-1, VLA-4, sLeX) and lymphoid activation markers (MHC class II, IL-2R) were demonstrated in liver biopsies by immunohistochemistry. Five biopsies from patients with normal graft function and without rejection or infection were used as controls for immune staining, and ten biopsies with acute rejection but without infection were used as positive controls. RESULTS: Biopsy histology demonstrated mild to moderate lymphocyte infiltration associated with HHV-6 infection. HHV-6 significantly (P < or = 0.05) increased the vascular expression of ICAM-1 and VCAM-1, and the number of graft infiltrating lymphocytes positive for LFA-1, VLA-4 and class II antigens. A total of 3/8 grafts developed chronic rejection. CONCLUSIONS: HHV-6 infection increased adhesion molecule expression and lymphocyte infiltration in liver allografts.     

Temporal motifs reveal homophily,gender-specific patterns,and group talk in call sequences

Recent studies on electronic communication records have shown that human communication has complex temporal structure. We study how communication patterns that involve multiple individuals are affected by attributes such as sex and age. To this end, we represent the communication records as a colored temporal network where node color is used to represent individuals’ attributes, and identify patterns known as temporal motifs. We then construct a null model for the occurrence of temporal motifs that takes into account the interaction frequencies and connectivity between nodes of different colors. This null model allows us to detect significant patterns in call sequences that cannot be observed in a static network that uses interaction frequencies as link weights. We find sex-related differences in communication patterns in a large dataset of mobile phone records and show the existence of temporal homophily, the tendency of similar individuals to participate in communication patterns beyond what would be expected on the basis of their average interaction frequencies. We also show that temporal patterns differ between dense and sparse neighborhoods in the network. Because also this result is independent of interaction frequencies, it can be seen as an extension of Granovetter’s hypothesis to temporal networks.Social networks have been studied since the early 20th century, and their significance to the performance and well-being of individuals is now widely recognized (1, 2). The availability of electronic communication records—data on mobile phone calls, e-mails, tweets, and messages in social networking sites—has, however, created unprecedented opportunities for studying social networks (3, 4), allowing the analyzing of human interaction networks at the societal scale (5–7), studying their mesoscale structure (8), and carrying out experiments with tens of millions of subjects (9).Communication records are typically studied by constructing an “aggregate network” where the nodes correspond to people, edges denote their relations as inferred from the communication data, and tie strengths are accounted for by edge weights representing communication frequency. Although this approach has been immensely successful, it disregards all information contained in the detailed timings of communication events. As an example, individuals who appear highly connected in the aggregate network might only interact with a small number of acquaintances at a time (10).Human communication has been shown to have rich temporal structure (11–13), and one of the challenges of computational social science is to understand this rich behavior. Although temporal inhomogeneities can be partially attributed to circadian and weekly patterns (12, 14), detailed analysis has shown that they have more fundamental origins (13, 15–17). Human communication is known to be intrinsically bursty (11, 13, 18, 19) and contain strong pairwise correlations of interaction times (13).“Homophily” refers to the well-documented tendency of individuals to interact with others similar to them with respect to various social and demographic factors (20–22). Because social networks act as conduits of information, homophily limits the information that individuals can receive. Although sex homophily is known to be less strong than homophily by age, race, or education (22), sex-related differences in communication have been documented at least in instant messaging (23), Facebook (24), and the use of both domestic (25) and mobile phones (26). However, not much is known about patterns involving multiple individuals, or the influence of factors such as sex or age on communication patterns. This is the focus of the present article.Increased awareness about the importance of temporal information in various empirical datasets has led to the emergence of the concept of “temporal networks,” a general framework for studying time-dependent interactions between nodes (27). Here, we study communication patterns of multiple individuals within this framework. We represent communication records as a “colored” temporal network where node colors are used to refer to individuals’ attributes. We then identify “temporal motifs” in these data to summarize their mesoscale temporal structure (28) and develop a null model that identifies differences between the relative occurrence of node colors in temporal motifs so that these differences are independent of the structure of the aggregate network. This choice of null model assures that all results presented in this article are independent of any previous results obtained by studying static communication networks where link weights correspond to communication frequency.Using a large dataset of mobile phone calls, we find significant differences in the occurrence of mesoscale communication patterns. We identify “temporal homophily,” overrepresentation of temporal patterns that contain similar nodes beyond that predicted by the structure of the aggregate network. By using event colors in addition to node colors, we also find consistent and robust differences between events occurring in dense and sparse neighborhoods of the aggregate network. Because this result is independent of the aggregate network, it can be seen as a temporal extension of Granovetter’s hypothesis about the correlation of local density and edge weights (29).     

Localization of Glial Cell Line-derived Neurotrophic Factor (GDNF) mRNA in Embryonic Rat by In Situ Hybridization

The localization of glial cell line-derived neurotrophic factor (GDNF) mRNA was studied by in situ hybridization in rat from embryonic (E) day E10 to E15. At E10, GDNF mRNA is found in the urogenital field and the cranial part of the gut. At E11, the most abundant expression of GDNF mRNA is seen in the epithelial cells of the second, third and fourth pharyngeal pouches, the third and fourth pharyngeal arches and pharynx. Also mesenchymal cells of the gut and mesonephric tubules contain GDNF mRNA. At E13, expression is observed in the mesenchymal cell layers of the oesophagus, intestine and stomach, the mesenchymal cells around the condensing cartilages and metanephric kidney mesenchyme. Also, the epithelia of Rathke's pouch and pharynx are intensely labelled. High expression of GDNF mRNA continues at El5 in kidney, gastrointestinal tract and cartilage. At that stage, GDNF mRNA is seen also in whisker pad and skeletal muscles. The distribution of GDNF mRNA in embryonic rat suggests important roles for GDNF in the early differentiation of the kidney tubules, the innervation of the gastrointestinal tract and the differentiation process of the cartilage and muscle. Our results indicate novel functions for GDNF outside the nervous system.     

The width of radiologically-defined attached gingiva over deciduous teeth

Abstract The aim of the present cross-sectional study was to radiologically investigate the continuous eruption process in the deciduous dentition by assessing the difference in the width of radiologically-defined attached gingiva (RAG) in 6-year-old and 10-year-old children. The group of 6-year-olds had predominantly deciduous teeth and the 10-year-olds were in their mixed dentition period. The mucogingival junction was revealed with Schiller's iodine solution and marked mid-labially along the long axis of each tooth with a piece of metal wire prior to taking panoramic radiographs. The width of RAG over deciduous canines and molars was measured from the cementoenamel junction to the mucogingival junction. A significant increase in the width of RAG was found from 6 to 10 years of age.