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Objectives In this study we assess how different Facebook (FB) posts resonate with parents hesitant about HPV vaccination and how to engage parents in positive dialogues on FB. Background Vaccination against human papillomavirus (HPV) was successfully introduced in the Danish childhood vaccination program in 2009 for 12 year-old girls, with coverage reaching approximately 90%. However, negative public debate questioning the safety of the vaccine coincided with a rapid decline in vaccination coverage from 2015. In May 2017, we launched the national campaign Stop HPV – stop cervical cancer with the aim to rebuild trust in the HPV vaccine and increase vaccination coverage. We used a FB page and a social media strategy to engage the campaign’s primary target group: mothers hesitant about HPV vaccination of their daughters. Methods We analyzed a variety of posts on the FB page Stop HPV – stop cervical cancer posted from May 2017 to December 2017. We performed analysis documenting post reach, engagement in the posts and sentiment (positive, neutral or negative) of the comments. Focus groups were recruited to provide data about attitudes to the posts and the responses from the FB management team. Results 84 unique posts were published on the FB page from May 2017 to December 2017 reaching 3,476,023 individual FB profiles. In focus groups, parents requested more in-depth information. However, analyses of FB posts and sentiment of comments showed that personal stories generated higher engagement rates and more positive dialogues compared to factual posts. Conclusion The FB page Stop HPV – stop cervical cancer has successfully reached and engaged FB users in dialogue about HPV vaccination. Personal stories are effective in creating positive dialogues on FB. However, it remains important to provide factual information to parents to enable informed decision making about HPV vaccination.

Objective To evaluate whether the social media strategy developed for the campaign Stop HPV – stop cervical cancer was successful at engaging target groups in communication regarding HPV vaccination. Introduction In 2009, the Human Papillomavirus (HPV) vaccine became part of the Danish childhood vaccination program to protect Danish girls from cervical cancer. In 2015, after a period of massive media coverage questioning the safety of the HPV vaccination, a rapid decline in HPV vaccination coverage was observed. An information campaign was therefore launched in May 2017 to address HPV vaccination hesitancy. The social media strategy ‘Heart-brain communication’ combined facts and emotions through varied content. Community management guidelines were worked out to ensure that there was positive dialogue. Key Point Indicators (KPI) for Engagement Rate (ER) and Click Through Rate (CTR) were chosen to uphold engagement and traffic from Facebook to the website. The KPIs were used to measure effectiveness. Results In January 2019, the social media campaign had reached 8,020,000 people with an average of 127 comments per post. The average ER from May 2017 to halfway through 2018 was 6.07% and the CTR was 2.09%. The content subgroup personal stories was the most effective in creating positive dialogue. One year after the launch of the campaign, the number of positive comments had increased from less than 50% to approximately 75%. Conclusion A comprehensive social media strategy using ‘heart-brain communication’ proved useful in a campaign for HPV vaccination. The success of the social media strategy was due to meticulous planning prior to launching the campaign, the use of content subgroups, the allocation of adequate resources for community management, the empirical analysis of content, and the use of evaluation results as guidance for the production of new content.

BACKGROUND: Patients with active acromegaly exhibit insulin resistance despite a lean phenotype whereas controlled disease improves insulin sensitivity and increases fat mass. The mechanisms underlying this paradox remain elusive, but growth hormone (GH)-induced lipolysis plays a central role. The aim of the study was to investigative the molecular mechanisms of insulin resistance dissociated from obesity in patients with acromegaly.METHODS: In a prospective study, twenty-one patients with newly diagnosed acromegaly were studied at diagnosis and after disease control obtained by either surgery alone (n=10) or somatostatin analogue (SA) treatment (n=11) with assessment of body composition (DXA scan), whole body and tissue-specific insulin sensitivity and GH and insulin signalling in adipose tissue and skeletal muscle.FINDINGS: Disease control of acromegaly significantly reduced lean body mass (pINTERPRETATION: In conclusion, the study support that uncontrolled lipolysis is a major feature of insulin resistance in active acromegaly, and is characterized by upregulation of PTEN and suppression of insulin signalling in both muscle and fat.FUNDING: This work was supported by a grant from the Independent Research Fund, Denmark (7016-00303A) and from the Alfred Benzon Foundation, Denmark.

Background: Olfactory identification deficits are present in individuals with schizophrenia and their unaffected first-degree relatives, while deficits are less pronounced in individuals with bipolar disorder. We hypothesized that children with familial high-risk for schizophrenia (FHR-SZ) show olfactory identification deficits compared to population-based controls (PBC), and that children with familial high-risk for bipolar disorder (FHR-BP) perform intermediate. Furthermore, we investigated potential relationships with psychopathology, cognition, and home environment. Methods: Olfactory identification was assessed at age 7 in 184 children with FHR-SZ, 106 children with FHR-BD, and 186 PBC with the Brief Smell Identification Test (BSIT). BSIT total score and the proportion of children scoring below pre-defined cut-off scores were the outcomes. Potential relationships with psychopathological, cognitive, and home environmental variables were conducted using hierarchical and logistic multiple regression analyses. Outcomes: ANOVA revealed no between-group differences in olfactory identification. Chi-square test of independence showed a significant greater proportion of boys with FHR-SZ than population-based boys with an abnormal olfactory identification (p

In the present study, the impact on peptide properties of labelling peptides with the fluorophore TAMRA or the selenium (Se) containing amino acid SeMet was evaluated. Three differently labelled variants of the cell-penetrating peptide (CPP) penetratin (Pen) were synthesized, PenM(Se), TAMRA-PenM(Se) and TAMRA-Pen. The labelled peptides were characterized in terms of hydrodynamic radius, secondary structure during peptide-membrane interaction, effect on membrane leakage induction, uptake efficiency in HeLa cells. Furthermore, stability of peptides and identities of degradation products in cell media and cell lysate were evaluated. TAMRA-labelling increased the hydrodynamic radius of Pen and PenM(Se) significantly. Labelling with Se caused no or minimal changes in size, secondary structure and membrane leakage induction in concentration levels relevant for cellular uptake studies. Similar degradation patterns of all labelled peptides were observed in HBSS media; degradation was mainly due to oxidation. Cellular uptake was significantly higher for the TAMRA labelled peptides as compared to Se-labelled Pen. Extensive degradation was observed in media during cellular uptake studies, however, in all cell lysates, primarily the intact peptide (PenM(Se), TAMRA-PenM(Se) or TAMRA-Pen) was observed. Selenium labelling caused minimal alteration of the physicochemical properties of the peptide and allowed for absolute quantitative determination of cellular uptake by inductively coupled plasma mass spectrometry. Selenium is thus proposed as a promising alternative label for quantification of peptides in general, altering the properties of the peptide to a minor extent as compared to commonly used peptide labels.

Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) show great potential as drug delivery vectors and new antibiotic drug entities, respectively. The current study deals with the properties of a variety of peptide analogs derived from the well-known CPP penetratin as well as octaarginine and different Tat sequences. The effects of peptide length, guanidinium content, and sequence of non-cationic residues were assessed in mammalian and bacterial cells. The arginine (Arg) content in the penetratin analogs was found to influence eukaryotic cell uptake efficiency, antimicrobial activity towards both Gram-positive and Gram-negative bacteria as well as eukaryotic cell viability. All examined analogs retained the ability to cross eukaryotic membranes giving rise to a distribution within the vacuolar apparatus. Interestingly, a series of shuffled analogs of penetratin with the cationic residues in conserved positions, attain the same α-helical conformation as native penetratin in the presence of cholesterol-containing liposomes, while conformational differences were observed in the presence of highly anionic liposomes. While the antibacterial effect of the two groups of peptides was similar, the eukaryotic cellular uptake of the shuffled analogs was noticeably lower than for native penetratin. Moreover, a point substitution of Met to Leu in native penetratin had no influence on eukaryotic cellular uptake and antimicrobial effect, and only a minor effect on cytotoxicity, in contrast to the fact that the same substitution in the shuffled analog gave rise to reduced eukaryotic cellular uptake while increasing the antibacterial effect and cytotoxicity.

Preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. The development, production and application of emergency vaccinations are the important measures against such threats. Vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the Spanish flu, the polio epidemics in the 1950s, or the SARS outbreak in 2003 if its spread had not been contained in time. Given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. However, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. In the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in Europe by focusing on public–private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies.

Limited specificity of the tuberculin skin test incited the development of the intradermal Mycobacterium tuberculosis-specific rdESAT-6 skin test. Animal studies have shown, however, that there is a possible risk of sensitization when repeated injections of rdESAT-6 are given. The aim of this phase 1 open clinical trial was to assess the sensitization risk and safety of repeated administration of rdESAT-6 reagent in 31 healthy adult volunteers. Three groups of volunteers received two fixed doses of 0.1 microg rdESAT-6 28, 56 or 112 days apart, respectively. After the second injection, the diameter of induration and/or redness at the injection site was measured and taken as a possible sensitization reaction if5mm. In vitro interferon gamma (IFN-gamma) responses were measured as supportive evidence. Local adverse reactions at the injection site and adverse events were recorded. One out of 31 (3%) volunteers showed a positive skin reaction (sensitization) upon a second injection of rdESAT-6 after 28days and an increased IFN-gamma response to ESAT-6. For 7 (23%) of the volunteers, local adverse reactions related to the product were registered, but all reactions were mild and predictable. In conclusion, repeated injections of the rdESAT-6 skin test reagent are safe, and sensitization occurs at a low rate, especially if the time span between succeeding doses is wide.

Genetic susceptibility towards clinical tuberculosis has been proposed in several population studies. We investigated whether polymorphisms in the candidate genes encoding solute carrier 11a1 protein (SLC11A1 formerly NRAMP1), mannose-binding lectin (MBL2) and Vitamin D receptor (VDR) were associated with tuberculosis in an East-African setting. Four hundred and forty-three culture positive pulmonary tuberculosis patients and 426 controls from Mwanza district in the northern part of Tanzania were prospectively included. Polymorphisms in the candidate genes were detected by different PCR-based techniques. A significant association between pulmonary tuberculosis and a microsatellite marker in the 5′(CA) n locus in the SLC11A1 gene compared with controls (38% versus 30% odds ratio 1.45, 95% CI: 1.06–1.9, P = 0.014) was observed. The association was apparent only in HIV negative tuberculosis patients. No association with tuberculosis was seen with 3 other SLC11A1 loci investigated, which previously have been associated with tuberculosis in other populations or with MBL2 and VDR polymorphisms. The tuberculosis associated microsatellite marker was situated on different SLC11A1 haplotypes. In this cohort a microsatellite marker in the 5′(CA) n locus situated in the SLC11A1 gene was associated with tuberculosis. The observed association was seen only in HIV negative patients suggesting that this genetic susceptibility for tuberculosis may be surpassed by co-infections.

The locus coeruleus is the largest cluster of noradrenaline-producing neurons in the brain and has been involved in regulating attention. The neurotransmitter system contributes to the initiation and maintenance of forebrain activity as well as modulation of the collection and processing of sensory information. This makes locus coeruleus a target of interest in the study of possible structural changes in the brains of subjects with chronic schizophrenia. Uniform sampling and optical disectors were used for estimation of total neuron numbers and the rotator principle for estimation of mean cell volume. This study estimated the bilateral total number of pigmented neurons in the locus coeruleus of schizophrenic and control subjects and found no difference between the two; schizophrenic subjects have 37,400 (coefficient of variation = CV = SD/mean = 0.28), control subjects have 35,500 (CV = 0.19), p = 0.64. The average volume of the cell perikaryon of pigmented neurons was measured in both groups and showed a significant larger cell volume in the locus coeruleus of schizophrenic compared to control subjects; mean locus coeruleus cell volume was 58,400 μm3 (CV = 0.31) in schizophrenic subjects, which is 55% larger than the 37,600 μm3 (CV = 0.33) found in control subjects, a difference of 20,800 μm3 (p = 0.009). The fixation time was significantly longer for the schizophrenic brains with an average of 169 months compared to 88 months for the control brains. No relation was found between total numbers or geometric mean volume of the pigmented cells and fixation time.

A multidisciplinary study to investigate 2,5-hexanedione (2,5-HD)-induced CNS-neurotoxicity and its proposed potentiation by acetone (AC) was conducted. Neurobehavioral testing, estimation of the brain-swelling reaction, neuropathological and morphometric measurements as well as synaptosomal 5-hydroxytryptamine (5-HT) uptake were evaluated. Male Wistar rats were exposed through their drinking water, for seven weeks, either to 0.5% 2,5-HD alone or to 0.5% 2,5-HD in combination with 0.5% AC. This 2,5-HD dose is known to cause neurotoxicity in the peripheral nervous system. Exposed animals were compared to a control group that received tap water. Acquisition but not performance of spatial learning, as measured in the radial 8-arm maze, was significantly inhibited by the coexposure to 2,5-HD and AC. Brain weights of rats exposed to 2,5-HD alone and to 2,5-HD and AC in combination, were slightly, albeit significantly, reduced. Synaptosomal high-affinity 5-HT uptake rate and uptake capacity were significantly reduced by 2,5-HD alone and in combination with AC. The morphometric results are reported in a companion paper. In conclusion, the present findings indicate that 2,5-HD is a CNS-neurotoxicant. The hypothesis about AC potentiation of 2,5-HD CNS-neurotoxicity was supported.

An efficient method for the unbiased estimation of the total number of neurons in rat brain cortex is presented. The method is reasonable fast, the counting procedure takes 2-3 h per rat, and gives an estimate of the total neuron number in cortex cerebri with an CE of 0.10. The rat cerebral cortex is found to have a mean volume of 253 mm3 and to contain a mean of 21 million neurons. The method has been used in a neurotoxicologic study, in which rats were given toluene perorally in doses of 200, 400 and 800 mg/kg/day, respectively, for 12 weeks, followed by an exposure-free period of 4 weeks. The total number of neurons in rat brain cortex cerebri showed no significant difference between exposed and non-exposed animals. The applicability of the method is discussed.

At two scientific conferences in 1985, one in Copenhagen sponsored by the Nordic Council of Ministers and the World Health Organization (WHO), the other in Raleigh, NC, it was concluded that chronic toxic encephalopathy may develop following long-term occupational exposure to organic solvents (1,2). The terms organic affective syndrome, mild and severe chronic toxic encephalopathy were suggested for this condition describing increasing severity. In May 1990, a conference on organic solvents and the nervous system was held in Copenhagen sponsored by the Commission of the European Communities and the Danish Ministry of the Environment (3). Scientists and representatives from the governments, industries, and labour organisations from the EEC and US participated.

Previous controlled trials with oral administration of allergen have not demonstrated any treatment effect in patients with allergic rhinoconjunctivitis or asthma. In the present double-blind, placebo-controlled trial, we have tested the effect of oral immunotherapy in adult patients with birch pollinosis. Thirty-nine patients completed this 18-month study comprising two birch pollen seasons. The patients received enterosoluble capsules daily, and the actively treated patients reached a cumulated dose of 280 times 10 6 biologic units of birch pollen extract, which is about 200 times higher than the dose used in conventional subcutaneous immunotherapy. We found a significant decrease in eye symptom scores and conjunctival sensitivity to birch pollen, as determined by conjunctival provocation test, as well as a numerical but nonsignificant decrease in nasal symptom scores, nasal sensitivity as determined by nasal provocation test, and antiallergic medication. The treatment was safe, and only a few slight side effects were observed. We thus conclude that our study demonstrates a clinical effect of oral immunotherapy in birch pollinosis.