Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium.

BACKGROUND: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. PATIENTS AND METHODS: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). RESULTS: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. CONCLUSIONS: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.

Aerobic interval training in standard treatment of out-patients with schizophrenia: a randomized controlled trial.

OBJECTIVE: To evaluate the feasibility and effects of integrating aerobic interval training (AIT) in standard care of out-patients with schizophrenia on aerobic capacity and conventional cardiovascular disease (CVD) risk factors. METHODS: Out-patients with schizophrenia spectrum disorder were randomized to the following: 1) a training group (TG), performing AIT 2 day/week at the clinic with adherence support from municipal services; or 2) a control group (CG), given two AIT sessions and encouraged to exercise on their own. Feasibility was assessed through retention/adherence. V˙O2peak was measured directly along with conventional CVD risk factors before and after 12 weeks. RESULTS: Of 48 out-patients, 16/25 and 18/23 completed the TG and CG respectively. After 12 weeks, V˙O2peak was higher (2.7 ± 4.8 ml/kg/min, P < 0.01) in the TG compared with the CG. The TG improved V˙O2peak by 3.1 ± 3.7 ml/kg/min (P < 0.01), while no change in the CG was observed. No intergroup difference in weight, body mass index (BMI), waist circumference, blood pressure, lipids, or glucose at posttest was observed. Weight (1.9 ± 4.0 kg, P < 0.05) and BMI (0.5 ± 1.1 kg/m2 , P < 0.05) increased in the CG, with no change in the TG. CONCLUSION: AIT, combined with adherence support, of out-patients with schizophrenia was feasible, improved V˙O2peak , and may be integrated in standard care. (ClinicalTrials.gov identifier: NCT02743143).

Maximal strength training improves musculoskeletal health in amphetamine users in clinical treatment.

Amphetamine use leads to impaired skeletal health and elevated risk of osteoporosis. In the current study, we document that maximal strength training (MST), as a part of clinical treatment, works as a countermeasure, improving muscle force generating capacity, body composition, and skeletal health at sites particularly prone to osteoporotic fractures. INTRODUCTION: Amphetamine users have attenuated musculoskeletal health. MST with heavy loads, few repetitions, and emphasis on maximal mobilization in the concentric phase may increase muscle force generating capacity and skeletal health. This study investigated if MST-induced improvements in force generating capacity improved bone mineral density (BMD), trabecular bone score, and body composition in amphetamine users participating in 3-months clinical treatment. METHODS: Of 40 randomized patients, 23 completed the study: 11 in the supervised training group (TG; 8 men, 3 women, 34 ± 10 years) and 12 in the control group (CG; 9 men, 3 women, 32 ± 8 years). The TG performed hack-squat MST three times a week for 12 weeks with an intensity of ~90% of one repetition maximum (1RM). Both groups attended conventional clinical treatment. Pre-training and post-training, we assessed hack-squat 1RM and rate of force development (RFD), BMD, body composition and trabecular bone score by dual X-ray absorptiometry, and serum bone metabolism markers. RESULTS: MST induced increases in 1RM (70%) and RFD (86%), and resulted in BMD improvements at lumbar spine (3.6%) and total hip (2.4%); all improvements were different from CG (p < 0.05). Both the 1RM and RFD increases were associated with BMD improvements (lumbar spine: r = 0.73 (1RM), r = 0.60 (RFD); total hip: r = 0.61 (1RM); all p < 0.05). No differences were observed in trabecular bone score or bone metabolism markers. CONCLUSIONS: MST improved force generating capacity and skeletal health at sites prone to bone loss in amphetamine users, and advocate that MST should be implemented as a clinical strategy to restore the patients' musculoskeletal health.

Breast cancer and ductal carcinoma in situ among women with prior squamous or glandular precancer in the cervix: a register-based study.

BACKGROUND: Human papillomavirus and hormonal contraceptives may be risk factors for cervical precancer and malignant breast tumours. METHODS: Standardised incidence ratios (SIRs) of malignant breast tumours during 1970-2008 were estimated separately for women with prior squamous and glandular cervical precancer. RESULTS: Women with squamous precancer and women with glandular precancer in the cervix had a significantly higher risk of malignant breast tumours than the general female population (SIR, 95% confidence interval: 1.10, 1.05-1.14 and 1.52, 1.11-2.08, respectively). INTERPRETATION: Shared risk factors or screening attendance may explain the excess risk of malignant breast tumours among women with a history of cervical precancer.

Chromatographic evaluation of structure selective and enantioselective retention of amines and acids on cellobiohydrolase I wild type and its mutant D214N.

The mechanisms of structure selective and enantioselective retentions of amines and acids on two chiral stationary phases based on wild type cellobiohydrolase I (CBH I) and its mutant D214N have been investigated. All the amino alcohols tested had an enantioselective site that overlaps with the catalytically active site of CBH I, whereas the enantioselectivity of prilocaine was not affected by the mutation. The hydroxyl group of the amino alcohols did not seem to be an important contributor to the total binding strength whereas a bromo substituent in the aromatic ring promotes a high enantioselectivity (alpha=7.05). Interestingly, the chiral recognition site of the acid warfarin overlaps with the binding site of the amino alcohols. Di-p-toluoyltartaric acid and dibenzoyltartaric acid were strongly retained probably due to electrostatic attraction, but no enantioselectivity was observed. The difference in retention characteristics for the amino alcohols on the two stationary phases was strongly pH-dependent. A change in elution order of different amino alcohols occurred when changing the pH from 5.0 to 7.0. The difference between the two phases was lower at low pH. The retention times could also be affected by ionic strength and by use of cellobiose as a mobile phase additive but no indication of ion-pair retention of the amines was observed, when adding hexanesulphonate as counter ion to the mobile phase. The temperature dependence of the retention of the enantiomers of propranolol at pH 7.0 on the mutant D214N was similar to what was earlier observed on the wild type CBH I at lower pH.

CIN 2/3 and cervical cancer in an organised screening programme after an unsatisfactory or a normal Pap smear: a seven-year prospective study of the Norwegian population-based screening programme.

OBJECTIVES: To estimate the risk of cervical intraepithelial neoplasia (CIN) 2/3 and invasive cervical cancer (ICC) in an organised screening programme after an unsatisfactory or a normal Pap smear. SETTING: A seven-year prospective cohort study of the Norwegian population-based co-ordinated screening programme based on the actual diagnostic and screening procedures performed. Observations of 526,661 women with a normal index Pap smear and 21,405 women with an unsatisfactory index Pap smear were made during 3.26 million women-years. METHODS: The risk of being diagnosed with CIN 2/3 or ICC was calculated by logistic regression for the first two years of follow-up. The hazard of being diagnosed with CIN 2/3 or ICC for the women who were not diagnosed during the two first years was estimated by non-parametrical survival regression. RESULTS: After two years of follow-up, 0.2% of the women were diagnosed with CIN 2/3 and 0.01% with ICC after a normal Pap smear. An unsatisfactory Pap smear indicated a 1.6-4.0 times higher risk of harbouring a CIN 2/3 or ICC compared to women with a normal Pap smear. No increased risk of ICC was found during long-term follow-up for the 70% of the women with an unsatisfactory Pap smear who were returned to ordinary screening. Prior series of low-grade Pap smears followed by a normal Pap were associated with an increased risk of CIN 2/3 and ICC. CONCLUSIONS: An unsatisfactory Pap smear indicates a risk of harbouring CIN II/III or ICC. Repeated Pap smears are adequate as a follow-up of an unsatisfactory Pap smear. Women with repeated series of equivocal/LSIL Pap smears followed by a normal Pap should be considered at high risk.

[A simple survey of post-traumatic stress disorders among Bosnian war refugees in Norway]. / Enkel kartlegging av posttraumatisk stressforstyrrelse hos bosniske krigsflyktninger i Norge.

150 Bosnian war refugees (100 men and 50 women) were followed for 12 months by means of a brief screening procedure to determine prevalence and course of symptoms of post-traumatic stress disorder. 88 men and 18 women had spent some time in Serbian concentration camps before arriving in Norway. A short check list for interview and a simple self-assessment questionnaire based on stressor and symptom criteria for post-traumatic stress disorders according to DSM-III-R were used three times. The number of persons with a diagnosis of post-traumatic stress disorder remained high throughout the period of observation. The presented diagnostic approach was compared with a comprehensive, standardized diagnostic test battery applied in a similar population of refugees by comparing the outcomes. For the majority of outcomes, no significant difference in prevalence was found. The experiences and results indicate that our approach is practicable, and can deliver diagnostic outcomes with acceptable validity.

Cellulases from the fungi Phanerochaete chrysosporium and Trichoderma reesei as chiral selectors in capillary electrophoresis: applications with displacer plugs and sample preconcentration.

The cellulases CBH 58 from the fungus Phanerochaete chrysosporium and CBH I from the fungus Trichoderma reesei were compared as chiral selectors in capillary electrophoresis (CE) applying the partial filling technique. Amines, e.g., norephedrine, two bambuterol analogs, as well as acids, e.g., di-p-toluoyl tartaric acid and dibenzoyl tartaric acid, which could not be enantioseparated in the liquid chromatographic use of the selectors, could be separated in the corresponding CE experiments. Due to the very high enantioselectivities, terbutaline, alprenolol and propranolol could be completely enantioresolved with selector plugs shorter than the sample plugs. The affinity of propranolol to CBH 58 was so high at pH 7.0 that neither of the enantiomers reached the detector; therefore, a plug of the displacing disaccharide cellobiose was injected after the sample to elute the propranolol enantiomers. The enantiomers could also be made to leave the capillary at opposite ends, thereby causing an infinite enantioresolution. A new preconcentration technique was introduced, which takes advantage of the very high affinity of propranolol to CBH 58 and the eluting ability of cellobiose. A 12.5 cm long plug of rac-propranolol could be preconcentrated and enantioseparated in a single procedure.

Nonradioactive, sequence-specific detection of RNA in situ by primed in situ labeling (PRINS).

A new method for the detection of RNA in situ is presented. It is based on sequence-dependent annealing of unlabeled specific oligonucleotide primers to intracellular RNA and subsequent chain elongation catalyzed by reverse transcriptase. Under the conditions described, biotin-labeled nucleotides can be incorporated and the cDNA synthesized in situ can thus be detected using fluorescein-conjugated avidin. Compared to traditional in situ hybridization the use of short oligonucleotide primers has the potential advantage of being better to discriminate between closely related RNA transcripts. Compared to in situ transcription with radioactive precursors we find it more attractive to use fluorescein-conjugated avidin as detection system because it allows a more detailed study of cell and signal simultaneously.