Roles of the hinge region and the DNA binding domain of the bovine papillomavirus type 1 E2 protein in initiation of DNA replication

The bovine papillomavirus (BPV-1) E2 protein is the regulator of extrachromosomal replication of papillomaviruses. The mutants with C-terminal truncations and in-frame internal deletions were constructed to study the role of structural domains of E2 in the initiation of DNA replication. We show that the replication initiation function of E2 is absolutely dependent on the ability of the protein to bind to DNA. Our study also confirms the borders of the functional domains of the E2 protein; residues 1-192 form the activation domain and residues 310-410 the DNA binding-dimerization domain. Some critical length and flexibility, but not the particular amino acid sequence between these two functional domains is required for the activity of the protein to support replication. The hinge region, including the major phosphorylation sites of E2, is also dispensable for the mediation of attachment of the BPV1 genome to the mitotic chromosomes.     

Young woman with hypophosphatasia: A case report

Hypophosphatasia is a rare inherited disease defined by teeth and bone mineralization impairment leading to depletion of tissue non‐specific alkaline phosphatase. We define a young woman diagnosed with hypophosphatasia (after several times alkaline phosphatase levels were low) was discovered following femoral fracture. A 30‐year‐old woman who presented for a history of early permanent teeth loss during the last 5 years and HPP‐like symptoms in family history and bone radiograph verified bowing, deficient mineralization, and symmetrical subtrochanteric stress fractures of femurs was referred to our clinic for further management. Blood test findings defined raised phosphorus levels on two occasions at 6.2 and 5.7 mg/dl and insufficient 25‐hydroxy vitamin D level. HPP early diagnosis and adequate treatment, depending on the clinical symptoms along with laboratory tests, could be effective in decreasing the suffering of the disease and side effects.     

Long-term effects of Internet-delivered cognitive behavioral therapy for depression in primary care – the PRIM-NET controlled trial

Objective: Internet-delivered cognitive behavioral therapy (ICBT) is recommended as an efficient treatment alternative for depression in primary care. However, only few previous studies have been conducted at primary care centers (PCCs). We evaluated long-term effects of ICBT treatment for depression compared to treatment as usual (TAU) in primary care settings.

Design: Randomized controlled trial.

Setting: Patients were enrolled at16 PCCs in south-west Sweden.

Participants: Patients attending PCCs and diagnosed with depression (n?=?90).

Interventions: Patients were assessed by a primary care psychologist/psychotherapist and randomized to ICBT or TAU. The ICBT included an ICBT program consisting of seven modules and weekly therapist e-mail or telephone support during the 3-month treatment period.

Main outcome measures: Questionnaires on depressive symptoms (BDI-II), quality of life (EQ-5D) and psychological distress (GHQ-12) were administered at baseline, with follow-ups at 3, 6 and 12 months. Antidepressants and sedatives use, sick leave and PCC contacts were registered.

Results: Intra-individual change in depressive symptoms did not differ between the ICBT group and the TAU group during the treatment period or across the follow-up periods. At 3-month follow-up, significantly fewer patients in ICBT were on antidepressants. However, the difference leveled out at later follow-ups. There were no differences between the groups concerning psychological distress, sick leave or quality of life, except for a larger improvement in quality of life in the TAU group during the 0- to 6-month period.

Conclusions: ICBT with weekly minimal therapist support in primary care can be equally effective as TAU among depressed patients also over a 12-month period.

Clinical trial registration: The trial was registered in the Swedish Registry, researchweb.org, ID number 30511.     

Accommodation of additional non-randomly sampled cases in a study of Helicobacter pylori infection in families

Epidemiological studies with two-stage designs typically gather information about some covariates from all study subjects in the first sampling stage, while additional data from only a subset of the subjects are collected in the second sampling stage. Appropriate analysis of two-stage studies maintains validity and can also improve precision. We describe an application of a weighted likelihood method, mean-score logistic regression, to accommodate data from a cross-sectional study of Helicobacter pylori infection in children, where the study sample was enriched with additional non-randomly sampled cases. The present work exemplifies how careful analysis of epidemiological data from complex sampling schemes can adjust for potential selection bias, improve precision and enable a more complete investigation of factors of interest. Our results highlight the importance of H. pylori infected mothers and siblings as risk factors for the infection in children in Sweden.     

European prices of newly launched reimbursable pharmaceuticals--a pilot study

High prices of new pharmaceuticals play an important part in rapidly rising pharmaceutical costs. Many countries try to curb these rising costs through control of the price of reimbursable medicines. There is, however, little internationally comparable information on prices. This study aimed to examine the prices of new, reimbursable pharmaceuticals in the EU member states. Price data were collected from eight products authorised by the EC in 2000. The prices of these products varied considerably. Wholesale prices were highest in those countries where manufacturers are free to set the prices of their products. Pharmacy margins and taxes, however, change the ranking of the most expensive or the cheapest countries.     

Imaging of dopamine transporters and D2 receptors in vascular parkinsonism: a report of four cases

Summary. The role of nuclear medicine imaging in the diagnosis of vascular parkinsonism (VP) has been addressed by only few studies up to now. Most previous reports suggest no or only mild impairment of DAT and D2 receptors in VP. In contrast, in four patients with VP, reported here, the combined DAT and D2 receptor SPECT showed highly unusual changes in the pre- and/or postsynaptic dopaminergic system. The possible value of combined DAT/D2 receptor SPECT imaging should be investigated by future prospective studies. These two authors contributed equally     

The relationship between local field potential and neuronal discharge in the subthalamic nucleus of patients with Parkinson's disease

Depth recordings in patients with Parkinson's disease (PD) have demonstrated prominent oscillatory activity in the beta frequency (13-35 Hz) band in local field potentials (LFPs) recorded from the region of the subthalamic nucleus (STN). Although this activity has been hypothesized to contribute to bradykinesia, it is unclear to what extent the LFP oscillations arise in the STN and are synchronous with local neuronal discharge. We therefore recorded both LFPs and multi-neuronal activity from microelectrodes inserted into STN in six PD patients (8 sides) during functional neurosurgery. As microelectrodes passed from above STN into STN, there was a pronounced increase in beta frequency band LFP activity. Furthermore, spike-triggered averages of LFP activity suggested that the discharges of neurons in STN were locked to beta oscillations in the LFP. The LFP is therefore likely to represent synchronous activity in populations of neurons in the STN of patients with PD.     

Group IIA phospholipase A2 content of tears in patients with atopic blepharoconjunctivitis

Background To determine the concentration of group IIA phospholipase A₂ (GIIAPLA₂) in tears of patients with atopic blepharoconjunctivitis (ABC), and to compare it with the GIIAPLA₂ concentration of tears in age-matched healthy controls.Methods The diagnosis of ABC was confirmed with a positive skin prick test and the presence of atopic dermatitis in lids. Conjunctival brush cytology was taken, and the cells including eosinophils, neutrophils, lymphocytes, squamous epithelial cells, columnar epithelial cells, metaplastic changes and the goblet cells were calculated separately. The GIIAPLA₂ concentration of tears was measured with a time-resolved fluoroimmunoassay in 29 patients with ABC (mean age 36.3±12.7 years) and 29 normal subjects (mean age 37.0±12.0 years).Results The GIIAPLA₂ concentration of tears in patients with ABC was 43.8±33.0 µg/ml, and in normal subjects it was 67.1±23.3 µg/ml. The difference was statistically significant (p=0.0018). The concentration of GIIAPLA₂ of tears was lowest in the subgroup of patients with ABC and dry eye (25.8 ±23.6 µg/ml), whereas it was only slightly decreased in patients with ABC and normal tear secretion (56.6±33.3 µg/ml). The difference between these two subgroups was statistically significant (p=0.011). There was no statistically significant correlation between the GIIAPLA₂ concentration of tears and the quantity of different conjunctival cells gathered by the brush cytology. However, an almost significant correlation was found between the GIIAPLA₂ concentration in tears and conjunctival eosinophils.Conclusions The results indicate that in patients with ABC the GIIAPLA₂ content of tears was decreased, without any dependence on the quantity of different conjunctival cells.     

C-band polymorphisms in lymphocytes of patients with ovarian or breast adenocarcinoma

To establish the significance of the variability of human chromosome constitutive heterochromatin areas (C-band variants) in a risk of malignancy, C-banding pattern study has been performed in 33 female patients with ovarian or breast adenocarcinoma. The control group included 180 healthy women. The following characteristics of C-bands on chromosomes #1, #9, and #16 were studied: (a) size, (b) size heteromorphisms and (c) inversions, using quantitative and semiquantitative methods of analysis. Our data show no significant difference in the presence of C-band size and location variants in chromosomes #1, #9, and #16 between the patients with adenocarcinoma of the ovary or breast and healthy women. From that we conclude that there is no causal association between the presence of C-band variants on chromosomes #1, #9, and #16 and an elevated risk of ovarian and breast adenocarcinoma.