Prostate cancer incidence in men with prostate-specific antigen below 3 ng/mL: The Finnish Randomized Study of Screening for Prostate Cancer

Prostate-specific antigen (PSA)-based screening for prostate cancer (PCa) can reduce PCa mortality, but also involves overdetection of low-risk disease with potential adverse effects. We evaluated PCa incidence among men with PSA below 3 ng/mL and no PCa diagnosis at the first screening round of the Finnish Randomized Study of Screening for PCa. Follow-up started at the first screening attendance and ended at PCa diagnosis, emigration, death or the common closing date (December 2016), whichever came first. Cox regression analysis was used to estimate hazard ratios and their confidence intervals (CI). Among men with PSA <3 ng/mL, cumulative PCa incidence was 9.1% after 17.6 years median follow-up. Cumulative incidence was 3.6% among men with baseline PSA 0 to 0.99 ng/mL, 11.5% in those with PSA 1.0 to 1.99 ng/mL and 25.7% among men with PSA 2 to 2.99 ng/mL (hazard ratio 9.0, 95% CI: 7.9-10.2 for the latter). The differences by PSA level were most striking for low-risk disease based on Gleason score and EAU risk group. PSA values <1 ng/mL indicate a very low 20-year risk, while at PSA 2 to 2.99 ng/mL risks are materially higher, with 4- to 5-fold risk for aggressive disease. Using risk-stratification and appropriate rescreening intervals will reduce screening intensity and overdetection. Using cumulative incidence of clinically significant PCa (csPCa) as the criterion, rescreening intervals could range from approximately 3 years for men with initial PSA 2 to 2.99 ng/mL, 6 years for men with PSA 1 to 1.99 ng/mL to 10 years for men with PSA <1 ng/mL.     

A trypsin-like protease from Bacteroides gingivalis: partial purification and characterization

Extracts of cell sonicates of Bacteroides gingivalis were shown to contain proteo-lytic enzymes capable of degrading connective tissue proteins. In this study, neutral proteolytic enzymes, i.e. collagenase and a trypsin-like protease, were isolated. The trypsin-like protease was readily separated from collagenase by affinity chromatography on Benzamidine-Sepharose. Proteases were further purified by gel filtration on Sephacryl S-200; apparent molecular weights of 35 kDa and 70 kDa were obtained for a trypsin-like protease and collagenase, respectively. Further characterization of the potent trypsin-like protease showed that the enzyme was inhibited by serine protease inhibitors phenylmethylsulfonyl fluoride and benzamidine and by metalloprotease inhibitor EDTA, as well as ascorbic acid. Activation of the enzyme was observed with reducing agents and human serum. The trypsin-like protease was found to be capable of degrading native type IV collagen and denatured type I collagen but not native type I collagen. Thus, we conclude that in addition to collagenase a potent trypsin-like protease from Bacteroides gingivalis may be involved in the etiopathogenesis of periodontal disease. Since the trypsin-like protease is able to degrade the basement membrane collagen (type IV) in the presence of human serum, this enzyme may be a potent virulence factor of Bacteroides gingivalis in relation to invasiveness and connective tissue destruction.     

Associations among different orofacial dysfunctions in 6-8 year olds.

Associations among several orofacial dysfunctions such as articulatory speech disorders, craniomandibular disorders (CMD) and problems in coordinating the orofacial muscles were examined in two groups of Finnish first-graders, i.e. children with and without speech disorders. In the whole sample of 287 subjects the mean age was 7.5 yr. A speech therapist diagnosed articulatory speech disorders and a phoniatrician examined the morphology and function of the articulators. Signs and symptoms of CMD, capacity for mandibular movement, and prevalence of occlusal interferences were examined by a dentist. Deviations in motor skills, but not in morphology of the articulators, were associated with speech disorders. The findings also suggested that capacity for mandibular movement, deviation of the jaw during maximal mouth opening and occlusal interferences were related to certain speech disorders among these 6-8 yr olds. Different orofacial dysfunctions appear to be associated with each other during growth.     

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.