Testing the large genome constraint hypothesis in tropical rhizomatous herbs: life strategies, plant traits and habitat preferences in gingers.

Plant species with large genomes tend to be excluded from climatically more extreme environments with a shorter growing season. Species that occupy such environments are assumed to be under natural selection for more rapid growth and smaller genome size (GS). However, evidence for this is available only for temperate organisms. Here, we study the evolution of GS in two subfamilies of the tropical family Zingiberaceae to find out whether species with larger genomes are confined to environments where the vegetative season is longer. We tested our hypothesis on 337 ginger species from regions with contrasting climates by correlating their GS with an array of plant traits and environmental variables. We revealed 16-fold variation in GS which was tightly related to shoot seasonality. Negative correlations of GS with latitude, temperature and precipitation emerged in the subfamily Zingiberoidae, demonstrating that species with larger GS are excluded from areas with a shorter growing season. In the subfamily Alpinioideae, GS turned out to be correlated with the type of stem and light requirements and its members cope with seasonality mainly by adaptation to shady and moist habitats. The Ornstein-Uhlenbeck models suggested that evolution in regions with humid climates favoured larger GS than in drier regions. Our results indicate that climate seasonality exerts an upper constraint on GS not only in temperate regions but also in the tropics, unless species with large genomes find alternative ways to escape from that constraint.

Suitability of machine learning models for prediction of clinically defined Stage III/IV periodontitis from questionnaires and demographic data in Danish cohorts.

AIM: To evaluate if, and to what extent, machine learning models can capture clinically defined Stage III/IV periodontitis from self-report questionnaires and demographic data. MATERIALS AND METHODS: Self-reported measures of periodontitis, demographic data and clinically established Stage III/IV periodontitis status were extracted from two Danish population-based cohorts (The Copenhagen Aging and Midlife Biobank [CAMB] and The Danish Health Examination Survey [DANHES]) and used to develop cross-validated machine learning models for the prediction of clinically established Stage III/IV periodontitis. Models were trained using 10-fold cross-validations repeated three times on the CAMB dataset (n = 1476), and the resulting models were validated in the DANHES dataset (n = 3585). RESULTS: The prevalence of Stage III/IV periodontitis was 23.2% (n = 342) in the CAMB dataset and 9.3% (n = 335) in the DANHES dataset. For the prediction of clinically established Stage III/IV periodontitis in the CAMB cohort, models reached area under the receiver operating characteristics (AUROCs) of 0.67-0.69, sensitivities of 0.58-0.64 and specificities of 0.71-0.80. In the DANHES cohort, models derived from the CAMB cohort achieved AUROCs of 0.64-0.70, sensitivities of 0.44-0.63 and specificities of 0.75-0.84. CONCLUSIONS: Applying cross-validated machine learning algorithms to demographic data and self-reported measures of periodontitis resulted in models with modest capabilities for the prediction of Stage III/IV periodontitis in two Danish cohorts.

COVID-19 as a mediator of interferon deficiency and hyperinflammation: Rationale for the use of JAK1/2 inhibitors in combination with interferon.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicits an interferon (IFN) deficiency state, which aggravates the type I interferon deficiency and slow IFN responses, which associate with e.g. aging and obesity. Additionally, SARS-CoV-2 may also elicit a cytokine storm, which accounts for disease progression and ultimately the urgent need of ventilator support. Based upon several reports, it has been argued that early treatment with IFN-alpha2 or IFN-beta, preferentially in the early disease stage, may prohibit disease progression. Similarly, preliminary studies have shown that JAK1/2 inhibitor treatment with ruxolitinib or baricitinib may decrease mortality by dampening the deadly cytokine storm, which - in addition to the virus itself - also contributes to multi-organ thrombosis and multi-organ failure. Herein, we describe the rationale for treatment with IFNs (alpha2 or beta) and ruxolitinib emphasizing the urgent need to explore these agents in the treatment of SARS-CoV-2 - both as monotherapies and in combination. In this context, we take advantage of several safety and efficacy studies in patients with the chronic myeloproliferative blood cancers (essential thrombocythemia, polycythemia vera and myelofibrosis) (MPNs), in whom IFN-alpha2 and ruxolitinib have been used successfully for the last 10 (ruxolitinib) to 30 years (IFN) as monotherapies and most recently in combination as well. In the context of these agents being highly immunomodulating (IFN boosting immune cells and JAK1/2 inhibitors being highly immunosuppressive and anti-inflammatory), we also discuss if statins and hydroxyurea, both agents possessing anti-inflammatory, antithrombotic and antiviral potentials, might be inexpensive agents to be repurposed in the treatment of SARS-CoV-2.

Oral contraceptives and the serotonin 4 receptor: a molecular brain imaging study in healthy women.

OBJECTIVE: Sex steroid hormones potently shape brain functions, including those critical to maintain mental health such as serotonin signaling. Use of oral contraceptives (OCs) profoundly changes endogenous sex steroid hormone levels and dynamics. Recent register-based studies show that starting an OC is associated with increased risk of developing depression. Here, we investigate whether use of OCs in healthy women is associated with a marker of the serotonin system in terms of serotonin 4 receptor (5-HT4R) brain imaging. METHODS: [11C]SB207145-PET imaging data on 53 healthy women, of whom 16 used OCs, were available from the Cimbi database. We evaluated global effects of OC use on 5-HT4R binding in a latent variable model based on 5-HT4R binding across cortical and subcortical regions. RESULTS: We demonstrate that OC users have 9-12% lower global brain 5-HT4R binding potential compared to non-users. Univariate region-based analyses (pallidostriatum, caudate, hippocampus, amygdala, anterior cingulate cortex, and neocortex) supported the global effect of OC use with the largest difference present in the hippocampus (-12.8% (95% CI [-21.0; -3.9], Pcorrected = 0.03). CONCLUSION: We show that women who use OCs have markedly lower brain 5-HT4R binding relative to non-users, which constitutes a plausible molecular link between OC use and increased risk of depressive episodes. We propose that this reflects a reduced 5-HT4R gene expression, possibly related to a blunted ovarian hormone state among OC users.

Spectral, spatial, and temporal characteristics of underwater ambient noise in the Beaufort Sea in 1994 and 2016.

Climate induced changes in the Arctic Ocean have severely impacted underwater acoustic communication and navigation; understanding underwater noise characteristics is critical to improving the performance of these operations. Ambient noise from the Beaufort Sea recorded in experiments more than 20 years apart (SIMI94 and ICEX16) are compared to determine differences that may be attributed to the region's rapidly changing environment. Spectral comparison shows noise within 20-350 Hz is ∼30 dB louder in 1994 than 2016; however, this is likely due to higher array self noise during SIMI94. Beamforming results show ambient noise vertical directionality is focused near the horizontal during SIMI94 but more spread in elevation during ICEX16, with a robust noise notch at the horizontal. Numerical modeling demonstrates that this difference may be attributed to ambient noise during ICEX16 being dominated by surface noise sources at discrete ranges rather than the historical assumption of a continuous and uniform distribution of sources. Temporal statistics of transient ice events show more acoustic activity during SIMI94 than ICEX16 and appear to support the new proposed surface source distribution for ICEX16.

A national register-based study of paediatric varicella hospitalizations in Denmark 2010-2016.

Varicella, usually a mild disease of childhood, can also cause complications and hospitalization. Universal varicella immunization is implemented in several countries worldwide, but not in Denmark. Taking advantage of unique national registers, we aimed to estimate the incidence of paediatric varicella hospitalizations and assess determinants for hospitalization. For this purpose, we designed a nationwide, retrospective register study of paediatric varicella hospitalizations and applied a case-cohort design and logistic regression analysis comparing hospitalized varicella patients to a sample of the entire paediatric population in Denmark. Varicella patients were identified in The Danish National Patient Register and referents were randomly selected from the Danish Civil Registration System. The incidence of paediatric varicella admissions was 11/100 000 children 0-18 years of age/year. Of admitted children 67·1% had complications and 30·0% had underlying disease. All categories of underlying disease significantly increased the odds of hospitalization as well as male gender and not having been born in Denmark. In conclusion, we found a considerable burden of paediatric varicella disease in Danish hospitals, of similar magnitude as in other European countries comparable to Denmark. With this study we have provided epidemiological data needed for considering implementation of varicella vaccine in Denmark.

Danish guidelines on management of otitis media in preschool children.

INTRODUCTION: Otitis media is one of the most common diseases in small children. This underlines the importance of optimizing diagnostics and treatment of the condition. Recent literature points toward a stricter approach to diagnosing acute otitis media (AOM). Moreover, ventilating tube treatment for recurrent AOM (RAOM) and chronic otitis media with effusion (COME) has become the most frequently performed surgical procedure in pre-school children. Therefore, the Danish Health and Medicines Authority and the Danish Society of Otorhinolaryngology, Head and Neck Surgery deemed it necessary to update the Danish guidelines regarding the diagnostic criteria for acute otitis media and surgical treatment of RAOM and COME. METHODS: The GRADE system (The Grading of Recommendations Assessment, Development and Evaluation) was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted between July and December 2014. The quality of the existing literature was assessed using AGREE II (Appraisal of Guidelines for Research & Evaluation), AMSTAR (assessing the Methodological Quality of Systematic Reviews), QUADAS-2 (Quality of Diagnostic Accuracy Studies), Cochrane Risk of Bias Tool for randomized trials and ACROBAT-NRSI (A Cochrane Risk of Bias Assessment Tool for Non-Randomized Studies). The working group consisted of otolaryngologists, general practitioners, pediatricians, microbiologists and epidemiologists. CONCLUSION: Recommendations for AOM diagnosis, surgical management for RAOM and COME, including the role of adenoidectomy and treatment of ventilating tube otorrhea, are proposed in the guideline.

Atopic conditions and brain tumor risk in children and adolescents--an international case-control study (CEFALO).

BACKGROUND: A number of epidemiological studies indicate an inverse association between atopy and brain tumors in adults, particularly gliomas. We investigated the association between atopic disorders and intracranial brain tumors in children and adolescents, using international collaborative CEFALO data. PATIENTS AND METHODS: CEFALO is a population-based case-control study conducted in Denmark, Norway, Sweden, and Switzerland, including all children and adolescents in the age range 7-19 years diagnosed with a primary brain tumor between 2004 and 2008. Two controls per case were randomly selected from population registers matched on age, sex, and geographic region. Information about atopic conditions and potential confounders was collected through personal interviews. RESULTS: In total, 352 cases (83%) and 646 controls (71%) participated in the study. For all brain tumors combined, there was no association between ever having had an atopic disorder and brain tumor risk [odds ratio 1.03; 95% confidence interval (CI) 0.70-1.34]. The OR was 0.76 (95% CI 0.53-1.11) for a current atopic condition (in the year before diagnosis) and 1.22 (95% CI 0.86-1.74) for an atopic condition in the past. Similar results were observed for glioma. CONCLUSIONS: There was no association between atopic conditions and risk of all brain tumors combined or of glioma in particular. Stratification on current or past atopic conditions suggested the possibility of reverse causality, but may also the result of random variation because of small numbers in subgroups. In addition, an ongoing tumor treatment may affect the manifestation of atopic conditions, which could possibly affect recall when reporting about a history of atopic diseases. Only a few studies on atopic conditions and pediatric brain tumors are currently available, and the evidence is conflicting.

Patterns of exposure to infectious diseases and social contacts in early life and risk of brain tumours in children and adolescents: an International Case-Control Study (CEFALO).

BACKGROUND: Infectious diseases and social contacts in early life have been proposed to modulate brain tumour risk during late childhood and adolescence. METHODS: CEFALO is an interview-based case-control study in Denmark, Norway, Sweden and Switzerland, including children and adolescents aged 7-19 years with primary intracranial brain tumours diagnosed between 2004 and 2008 and matched population controls. RESULTS: The study included 352 cases (participation rate: 83%) and 646 controls (71%). There was no association with various measures of social contacts: daycare attendance, number of childhours at daycare, attending baby groups, birth order or living with other children. Cases of glioma and embryonal tumours had more frequent sick days with infections in the first 6 years of life compared with controls. In 7-19 year olds with 4+ monthly sick day, the respective odds ratios were 2.93 (95% confidence interval: 1.57-5.50) and 4.21 (95% confidence interval: 1.24-14.30). INTERPRETATION: There was little support for the hypothesis that social contacts influence childhood and adolescent brain tumour risk. The association between reported sick days due to infections and risk of glioma and embryonal tumour may reflect involvement of immune functions, recall bias or inverse causality and deserve further attention.

SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies.

SB1518 is an innovative pyrimidine-based macrocycle that shows a unique kinase profile with selective inhibition of Janus Kinase-2 (JAK2; IC50=23 and 19 nM for JAK2(WT) and JAK2(V617F), respectively) within the JAK family (IC50=1280, 520 and 50 nM for JAK1, JK3 and TYK2, respectively) and fms-like tyrosine kinase-3 (FLT3; IC50=22 nM). SB1518 shows potent effects on cellular JAK/STAT pathways, inhibiting tyrosine phosphorylation on JAK2 (Y221) and downstream STATs. As a consequence SB1518 has potent anti-proliferative effects on myeloid and lymphoid cell lines driven by mutant or wild-type JAK2 or FLT3, resulting from cell cycle arrest and induction of apoptosis. SB1518 has favorable pharmacokinetic properties after oral dosing in mice, is well tolerated and significantly reduces splenomegaly and hepatomegaly in a JAK2(V617F)-driven disease model. SB1518 dose-dependently inhibits intra-tumor JAK2/STAT5 signaling, leading to tumor growth inhibition in a subcutaneous model generated with SET-2 cells derived from a JAK2(V617F) patient with megakaryoblastic leukemia. Moreover, SB1518 is active against primary erythroid progenitor cells sampled from patients with myeloproliferative disease. In summary, SB1518 has a unique profile and is efficacious and well tolerated in JAK2-dependent models. These favorable properties are now being confirmed in clinical studies in patients with myelofibrosis and lymphoma.

An evaluation of a behaviour assessment to determine the suitability of shelter dogs for rehoming.

We evaluated a scheme for assessing shelter dog behaviour, which used 28 tests and rated responses from 0 (positive response) to 5 (fear, tonic immobility, or escape attempts). The assessment was evaluated for 236 dogs, and was repeated by a different assessor for 39 dogs approximately 80 days after rehoming to determine relevance of individual test components. A new owner survey evaluated satisfaction with the dog. A total of 130 of 236 dogs passed (score 80) failed. Scores were mainly unaffected by dog type and environmental variables, but decreased if dog faeces from a previous test was present in the arena during a test. Shelter tests only correlated with repeat tests if there was no direct contact with assessors. Adopters were satisfied with their dogs, despite reporting some behaviour problems. The shelter assessment was therefore robust against most outside influences but did not predict responses to people well.

Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway.

Large conductance calcium-activated potassium (BK(Ca)) channels are membrane proteins contributing to electrical propagation through neurons. Calcitonin gene-related peptide (CGRP) is a neuropeptide found in the trigeminovascular system (TGVS). Both BK(Ca) channels and CGRP are involved in migraine pathophysiology. Here we study the expression and localization of BK(Ca) channels and CGRP in the rat trigeminal ganglion (TG) and the trigeminal nucleus caudalis (TNC) as these structures are involved in migraine pain. Also the effect of the BK(Ca) channel blocker iberiotoxin and the BK(Ca) channel opener NS11021 on CGRP release from isolated TG and TNC was investigated. By RT-PCR, BK(Ca) channel mRNA was detected in the TG and the TNC. A significant difference in BK(Ca) channel mRNA transcript levels were found using qPCR between the TNC as compared to the TG. The BK(Ca) channel protein was more expressed in the TNC as compared to the TG shown by western blotting. Immunohistochemistry identified BK(Ca) channels in the nerve cell bodies of the TG and the TNC. The beta2- and beta4-subunit proteins were found in the TG and the TNC. They were both more expressed in the TNC as compared to TG shown by western blotting. In isolated TNC, the BK(Ca) channel blocker iberiotoxin induced a concentration-dependent release of CGRP that was attenuated by the BK(Ca) channel opener NS11021. No effect on basal CGRP release was found by NS11021 in isolated TG or TNC or by iberiotoxin in TG. In conclusion, we found both BK(Ca) channel mRNA and protein expression in the TG and the TNC. The BK(Ca) channel protein and the modulatory beta2- and beta4-subunt proteins were more expressed in the TNC than in the TG. Iberiotoxin induced an increase in CGRP release from the TNC that was attenuated by NS11021. Thus, BK(Ca) channels might have a role in trigeminovascular pain transmission.

Proton pump inhibitors and risk of gastric cancer: a population-based cohort study.

Proton pump inhibitor (PPI) use leads to hypergastrinaemia, which has been associated with gastrointestinal neoplasia. We evaluated the association between PPI use and risk of gastric cancer using population-based health-care registers in North Jutland, Denmark, during 1990-2003. We compared incidence rates among new users of PPI (n=18,790) or histamine-2-antagonists (H2RAs) (n=17,478) and non-users of either drug. Poisson regression analysis was used to estimate incidence rate ratios (IRRs) adjusted for multiple confounders. We incorporated a 1-year lag time to address potential reverse causation. We identified 109 gastric cancer cases among PPI users and 52 cases among H2RA users. After incorporating the 1-year lag time, we observed IRRs for gastric cancer of 1.2 (95% CI: 0.8-2.0) among PPI users and 1.2 (95% CI: 0.8-1.8) among H2RA users compared with non-users. These estimates are in contrast to significant overall IRRs of 9.0 and 2.8, respectively, without the lag time. In lag time analyses, increased IRRs were observed among PPI users with the largest number of prescriptions or the longest follow-up compared with H2RA users or non-users. Although our results point to a major influence of reverse causation and confounding by indication on the association between PPI use and gastric cancer incidence, the finding of increased incidence among PPI users with most prescriptions and longest follow-up warrants further investigation.

Assay discrepancy in mild haemophilia A: entire population study in a National Haemophilia Centre.

Assay discrepancy in mild haemophilia, here defined by a significantly higher factor VIII (FVIII):C response by the one-stage procoagulant assay as compared with a two-stage enzymatic method, has repeatedly been reported in literature. The purpose of this study was to determine the overall prevalence of this phenomenon amongst mild haemophilia families from a population of 2.95 million inhabitants in the Western Danish region. Information was collected retrospectively through a thorough search of archives of the National Haemophilia Centre in Aarhus. We identified 109 patients with mild haemophilia A amongst whom 92 were eligible to enter the study. These represent a total of 53 unrelated families. Our data illustrate that this assay discrepancy pattern is found quite frequently amongst our mild haemophilia A families. While the ratio of FVIII:C chromogenic/FVIII:C clot values was quite consistent amongst patients belonging to same family pattern, ratios in the entire cohort of families ranged from 0.18 to 1.00. Selecting a cut-off level for the FVIII:C chromogenic/FVIII:C clot ratios at 0.7, 0.6 and 0.5, respectively, we found that 38 (72%), 27 (51%) and 19 (36%) of families, respectively, displayed this assay discrepancy. In 10 patients, the FVIII:C chromogenic level was inside the category of moderate haemophilia at >0.01-<0.05 IU mL(-1), pointing to a class-shift in the biochemical phenotype. In conclusion, our data illustrate a substantial prevalence of the assay discrepancy phenomenon amongst mild haemophilia A patients in our geographical area.

Persistent organohalogen contaminant burdens in Antarctic krill (Euphausia superba) from the eastern Antarctic sector: a baseline study.

A baseline for persistent organohalogen compound (POC) accumulation in the Antarctic keystone species, Antarctic krill (Euphausia superba) has been established for a 50 degrees longitudinal range of the eastern Antarctic sector. Samples of adult krill, caught from 12 sites distributed between 30 degrees and 80 degrees E (60-70 degrees S), were analysed for >100 organohalogen compounds including chlorinated pesticides, polychlorinated biphenyls (PCBs), polybrominated organic compounds and polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs). Organochlorine pesticides dominated measured krill contaminant burdens with hexachlorobenzene (HCB) as the single most abundant compound quantified. Krill HCB concentrations were comparable to those detected at this trophic level in both the Arctic and temperate northwest Atlantic, lending support for the hypothesis that HCB will approach global equilibrium at a faster rate than other POCs. Para, para'-dichlorodiphenylethene (p,p'-DDE) was detected at notable concentrations. Measurements of DDT and its degradation products provide an important baseline for monitoring the temporal and geographical influence of renewed, DDT usage for malaria-control in affected southern hemisphere countries. In contrast to the Arctic, PCBs did not feature prominently in contaminant burdens of Antarctic krill. The major commercial polybrominated diphenyl ether (PBDE) congeners -99 and -47 were quantified at low background levels with clear concentration spikes observed at around 70 degrees E , in the vicinity of modern, active research stations. The likelihood that local anthropogenic activities are supplementing low PBDE levels, delivered otherwise primarily via long range environmental transport, is discussed. The suspected naturally occurring brominated organic compound, 2,4,6-tribromoanisole (TBA), was a ubiquitous contaminant in all samples whereas the only PCDD/Fs quantifiable were trace levels of octachlorodibenzo-p-dioxin (OCDD) and 1,2,3,4,7,8/1,2,3,4,7,9-hexachlorodibenzofuran (HxCDF). With the aims of; i) Generating a robust and broadly applicable POC auditing platform for the scarcely studied eastern Antarctic sector; ii) Determining the compounds accumulating in Antarctic krill for further toxicity evaluation studies and iii) Establishing a baseline for Antarctic predator exposure to POCs, this study represents one of the most comprehensive reports of POC contamination of the Antarctic food web to date.

Use of NSAIDs, smoking and lung cancer risk.

We investigated the risk of lung cancer in relation to non-steroidal anti-inflammatory drugs (NSAIDs) among 573 cases and 857 sex- and age-matched controls for whom we had information on use of NSAIDs, from a prescription database covering all pharmacies in Denmark since 1995, and self-reported NSAID use, smoking habits and other potential confounders. Associations were expressed as odds ratios, assessed by logistic regression in unmatched analyses. After controlling for smoking habits, length of education and concomitant use of acetaminophen, we found a slightly decreased relative risk of 0.86 (95% confidence intervals, 0.65-1.14) for lung cancer associated with any use of NSAIDs. The risk decreased significantly (P=0.02) with increasing numbers of dispensed prescriptions per year during the 1-3 years before the index date with a relative risk of 0.49 (0.28-0.84) among those with four or more prescriptions per year during this period. Our findings suggest that regular use of NSAIDs is associated with a slightly or moderately reduced risk for lung cancer.

Perceived freedom in leisure and physical co-ordination ability: impact on out-of-school activity participation and life satisfaction.

BACKGROUND: Perceived freedom in leisure (PFL) is explored as a potential mechanism mediating relationships between physical co-ordination ability and both global life satisfaction and leisure-time physical activity participation for boys with differing levels of physical co-ordination ability. Understanding psychological mechanisms contributing to low rates of participation in physical activities for boys with developmental co-ordination disorder (DCD) is a clinical and research priority with potential to inform clinical interventions and preventive health initiatives. METHOD: Sixty boys aged 10-13 years with DCD and 113 boys without DCD completed self-report measures of PFL and life satisfaction. Seven-day leisure-time activity diaries and 12-month retrospective recall questionnaires were completed by parents. RESULTS: Lower self-appraisals of PFL and overall life satisfaction were found for boys with DCD compared with boys without DCD. PFL mediated relationships between physical ability and both life satisfaction and team sport participation. CONCLUSION: Perceived freedom in leisure, comprising self-appraisals of leisure needs satisfaction and competence, depth of involvement and perceived control over leisure outcomes, was a significant mechanism influencing leisure-time participation and life satisfaction for boys. The implications for effective intervention and preventive health programmes are discussed.

Aggressive periodontitis in a 16-year-old Ghanaian adolescent, the original source of Actinobacillus actinomycetemcomitans strain HK1651 - a 10-year follow up.

The highly leukotoxic JP2 clone of Actinobacillus actinomycetemcomitans is strongly associated with periodontitis in adolescents. Availability of the DNA sequence of the complete genome of A. actinomycetemcomitans strain HK1651, a representative strain of the JP2 clone (http://www.genome.ou.edu/act.html), has provided new possibilities in basic research regarding the understanding of the pathogenesis of A. actinomycetemcomitans in periodontitis. This case report describes the periodontal treatment of the original source of A. actinomycetemcomitans HK1651, a 16-year-old Ghanaian adolescent girl with aggressive periodontitis. The bacterial examination involved polymerase chain reaction analysis for presence of JP2 and non-JP2 types of A. actinomycetemcomitans. The treatment, including periodontal surgery supplemented by antibiotics, arrested the progression of periodontitis for more than 10 years. Initially, infection by A. actinomycetemcomitans, including the JP2 clone, was detected at various locations in the oral cavity and was not limited to the periodontal pockets. Post-therapy, the JP2 clone of A. actinomycetemcomitans disappeared, while the non-JP2 types of A. actinomycetemcomitans remained a part of the oral microflora.

Cancer risk among users of neuroleptic medication: a population-based cohort study.

It has been suggested that neuroleptic medication may decrease cancer risk. We compared cancer risks in a population-based cohort study of 25,264 users (>or=2 prescriptions) of neuroleptic medications in the county of North Jutland, Denmark, during 1989-2002, with that of county residents who did not receive such prescriptions. Statistical analyses were based on age-standardisation and Poisson regression analysis, adjusting for age, calendar period, COPD, liver cirrhosis or alcoholism, use of NSAID, and, for breast cancer, additionally for use of hormone therapy, age at first birth, and number of children. Use of neuroleptic medications was associated with a decreased risk for rectal cancer in both women and men (adjusted IRRs of 0.61 (95% confidence interval, 0.41-0.91) and 0.82 (0.56-1.19), respectively) and for colon cancer in female users (0.78; 0.62-0.98). Some risk reduction was seen for prostate cancer (0.87; 0.69-1.08), but breast cancer risk was close to unity (0.93; 0.74-1.17). Overall, treatment with neuroleptic medications was not related to a reduced risk of cancer, but for cancers of the rectum, colon and prostate there were suggestive decreases in risk.