An investigation into security, self-confidence and gender differences related to undergraduate education in Endodontics.

AIM: To analyse responses from dental practitioners (DPs) on how secure they felt as a newly graduated dentist, level of confidence or self-efficacy when performing root canal treatment (RCT), and if undergraduate (UG) education in Endodontics adequately met their needs in a dental practice. METHODOLOGY: An electronic questionnaire was sent to 459 dentists who graduated from the University of Bergen, Bergen, Norway, between 2008 and 2018. The survey consisted of questions with closed-end options and Likert scale (1-5). An open-ended free text option was always provided. RESULTS: A total of 314 (68.4%) DPs answered the questionnaire. Of these, 87 (27.8%) were men and 224 (71.3%) were women. Three respondents did not disclose their gender. As a newly graduated dentist, 37.3% of the respondents felt secure when performing RCT, 30.7% felt indifferent, and 32.0% felt insecure. The majority (72.4%) of respondents were either confident or very confident when performing RCT, 21.3% were indifferent, and 6.3% had little or no confidence. A majority of DPs (84.4%) self-evaluated the quality of their root fillings as good or very good, and 15.2% were indifferent. Only one DP selected 'not good' and none selected 'bad'. There were significant gender differences where male DPs felt more secure than female DPs when performing RCT (P < 0.001). A significantly larger number of men were very confident compared to women (P < 0.001). A logistic regression analysis using confidence as a dependent variable to predict self-efficacy revealed that DPs who felt secure when performing RCT as a newly graduated dentist had about 8 times more self-efficacy (odds ratio = 8.49) than those who were insecure or indifferent. Respondents who rated their quality of root fillings as good or very good had forty times more self-efficacy (odds ratio = 40.06) when performing RCT. UG education in endodontics was considered inadequate by 71.3% of the respondents where a significantly larger number of DPs (70%) wanted more clinical training (P < 0.05). About half the DPs (47.7%) stated that there was a need for lifelong learning with majority preferring hands-on courses and continuing dental education organized by dental associations. CONCLUSIONS: The results of this study suggest that there is a need to promote self-efficacy during UG education in Endodontics. Hands-on training is the preferred form of lifelong learning for DPs.

Quality of life of parents of mentally-ill children: a systematic review and meta-analysis.

AIMS: To examine the quality of life (QOL) of parents of children with a specific mental disorder (any age). METHODS: Relevant articles were searched using different databases. Articles were included that compared the QOL of parents with mentally-ill children to parents of healthy controls or norm values or provided the required data for this comparison. A meta-analysis was conducted to obtain an overall mean effect size estimate. Additional analyses were performed to assess publication bias and moderation. RESULTS: Twenty-six out of 10 548 articles met the pre-defined inclusion criteria. Most of these studies focused on attention-deficit/hyperactivity disorder or autism spectrum disorder, used clinical samples that mainly included males and young children and studied the QOL of mothers. The meta-analysis revealed that parents of mentally-ill children are experiencing a clinically relevant reduction in their QOL relative to parents of healthy children and norm values (g = -0.66). CONCLUSIONS: The compromised QOL of parents of mentally-ill children needs to be considered and addressed by health professionals who are in contact with them. The paper provides insights into existing research gaps and suggests improvements for subsequent work.

First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)--a systematic review and individual patient data meta-analysis.

BACKGROUND: To investigate prognosis and effects of first-line therapy in elderly primary central nervous system lymphoma (PCNSL) patients. PATIENTS AND METHODS: A systematic review of studies about first-line therapy in immunocompetent patients ≥60 years with PCNSL until 2014 and a meta-analysis of individual patient data from eligible studies and international collaborators were carried out. RESULTS: We identified 20 eligible studies; from 13 studies, we obtained individual data of 405 patients, which were pooled with data of 378 additional patients (N = 783). Median age and Karnofsky Performance Score (KPS) was 68 years (range: 60-90 years) and 60% (range: 10%-100%), respectively. Treatments varied greatly, 573 (73%) patients received high-dose methotrexate (HD-MTX)-based therapy. A total of 276 patients received whole-brain radiotherapy (median 36 Gy, range 28.5-70 Gy). KPS ≥ 70% was the strongest prognostic factor for mortality [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.41-0.62]. After a median follow-up of 40 months, HD-MTX-based therapy was associated with improved survival (HR 0.70, 95% CI 0.53-0.93). There was no difference between HD-MTX plus oral chemotherapy and more aggressive HD-MTX-based therapies (HR 1.39, 95% CI 0.90-2.15). Radiotherapy was associated with an improved survival, but correlated with an increased risk for neurological side-effects (odds ratio 5.23, 95% CI 2.33-11.74). CONCLUSIONS: Elderly PCNSL patients benefit from HD-MTX-based therapy, especially if combined with oral alkylating agents. More aggressive HD-MTX protocols do not seem to improve outcome. WBRT may improve outcome, but is associated with increased risk for neurological side-effects. Prospective trials for elderly PCNSL patients are warranted.

[Individualised parent counselling in paediatric practices for the reduction of second-hand smoke exposure of their children: a feasibility study]. / Individualisierte Beratung von Eltern in Kinderarztpraxen zur Reduktion der Passivrauchbelastung ihrer Kinder: eine Machbarkeitsstudie.

AIM: The aim of this study was to test the feasibility of a web-based programme provided by paediatric practices for counselling parents to reduce second-hand smoke exposure of their children. METHODS: Accompanying persons of children were systematically screened concerning tobacco smoking at their home in 2 Swiss paediatric practices. They were invited for programme participation if they or their partners smoked at home regularly. The web-based programme provided at least 1 computer-tailored counselling letter. Upto 3 additional counselling letters could be requested online by the participants over a period of 3 months. The letters were tailored according to the indoor smoking behaviour of the parents and considered individual barriers and resources for the establishment of a smoke-free home. Additionally, further information and advice could be requested on the programme website. Feasibility indicators were the participation rate, programme use, and programme evaluation by the participants. RESULTS: 3 055 (82.3%) of 3 712 accompanying persons of children in the paediatric practices were screened concerning tobacco smoking at their home. 96 (56.8%) of 169 eligible persons participated in the programme. 68 (70.8%) of the 96 programme participants could be reassessed at post assessment. 9 (15.0%) of 60 participants who provided a valid e-mail address requested more than one counselling letter. The counselling letters and the web-based programme were evaluated positively by the programme participants. CONCLUSION: Systematic screening combined with the provision of individually tailored counselling letters for parents to reduce second-hand smoke exposure of their children was feasible in paediatric practices. Possible strategies to in-crease the use and reach of the programme are -discussed.

[Brief text messaging (SMS)-delivered smoking cessation intervention for apprentices in vocational schools: a longitudinal intervention study for process and outcome evaluation]. / Kurzintervention zur Förderung der Tabakabstinenz via Short Message Service (SMS) bei Auszubildenden an beruflichen Schulen: Longitudinale Interventionsstudie zur Ergebnis- und Prozessevaluation.

OBJECTIVE: The aim of this study is to test the acceptance and efficacy of an individualised text messaging (SMS)-based intervention to support smoking cessation in apprentices of vocational schools. METHODS: The SMS program MyWay, which generated individualised text messages to support smoking cessation based on an online assessment and a weekly SMS assessment, was developed. The text messages were based on the Transtheoretical Model of Behavior Change and sent to the programme participants over a period of 3 months. The programme was tested in 62 school classes at 6 vocational schools in Bremen, Germany, where 1 086 apprentices participated in an online assessment addressing demographic and smoking related variables. RESULTS: A total of 415 persons (38%) fulfilled the inclusion criteria "daily cigarette smoking", "ownership of a cell phone" and "regular use of text messaging". Of these, 210 persons (51%) participated in the programme. A 6-month follow-up telephone interview for the evaluation of the SMS programme and the assessment of smoking-related variables could be conducted in 125 (60%) of the 210 programme participants. Compared to the baseline assessment, the smoking prevalence (7-day-point prevalence abstinence, 11%) and the intention to stop smoking (p<0.01) were higher at the 6-month follow-up. Furthermore, cigarette craving was lower at 6-month follow-up among persons who still smoked at this point in time (p<0.01). CONCLUSIONS: In comparison to other smoking cessation services, this intervention approach allows us to reach a substantial part of smokers in vocational schools. The text messaging programme is promising for the support of smoking cessation in young adults.

[Tobacco smoking and alcohol consumption among apprentices at vocational schools in West Pomerania, Germany]. / Tabakrauchen und Alkoholkonsum bei Auszubildenden an beruflichen Schulen in Vorpommern.

Little is known about tobacco smoking and health risk drinking among apprentices at vocational schools. The aim of this study was to determine the proportions of subjects who smoke or drink alcohol in a risky way, their preparedness to stop smoking, and the proportions of smokers and risk drinkers according to occupational groups and general school education. The methods included a survey of all apprentices in their first year of vocational training and all trainees in a course of preparation for occupation in a north-eastern region of Germany. All vocational schools of the study region participated. At the time of the survey, 77.9% of the apprentices were present. Among them, 99.8% (N=1 124) filled in questionnaires. The data revealed that among the total sample 61.2% were daily or less than daily current smokers. Among adults, 8.2%, among those at age 17 or younger 12.9% had a mean daily consumption of more than 12 grams (females) or more than 24 grams (males) of pure alcohol. These proportions were 12.6-18.0% among apprentices of blue collar occupations and 2.8-6.5% among apprentices of white collar or health occupations. Among subjects who had left school without graduation, 85.0%, and among those with the highest school education 36.9% were current smokers. It is concluded that vocational schools are a suitable and essential setting to reach a high risk population concerning tobacco smoking or unhealthy alcohol consumption.

First measurements of inclusive muon neutrino charged current differential cross sections on argon.

The ArgoNeuT Collaboration presents the first measurements of inclusive muon neutrino charged current differential cross sections on argon. Obtained in the NuMI neutrino beam line at Fermilab, the flux-integrated results are reported in terms of outgoing muon angle and momentum. The data are consistent with the Monte Carlo expectation across the full range of kinematics sampled, 0°<θ(µ)<36° and 0

[Internet and mobile phone interventions to decrease alcohol consumption and to support smoking cessation in adolescents: a review]. / Reduktion des Alkoholkonsums und Förderung der Rauchabstinenz bei Jugendlichen und jungen Erwachsenen mittels Internet und Mobiltelefon: ein Literaturüberblick.

OBJECTIVE: The aim of this study was to review the published literature on Internet and mobile phone interventions to decrease alcohol consumption and for smoking cessation in adolescents. METHODS: Electronic searches of PubMed, MEDLINE, Web of Science, PsycINFO, ERIC, and the Cochrane Register of Controlled Trials were conducted in August 2009. Additionally, reference lists of previously published reviews and meta-analyses within this topic were checked. Studies, published in scientific journals, containing English abstracts, and reporting results about the effectiveness of an intervention were included into the review. RESULTS: Initial searches in the literature databases identified 2 263 articles of which 31 were eligible for inclusion in this review: 19 articles address internet interventions to decrease alcohol consumption, 7 Internet interventions for smoking cessation, and 5 mobile phone text messaging interventions for smoking cessation. No articles concerning mobile phone interventions to decrease alcohol consumption in adolescents were identified. 16 out of the 19 studies that aimed at decreasing alcohol consumption by the use of the Internet were conducted in college or university students from the United States or New Zealand and the majority of these studies were based on the social norms approach. Good empirical evidence exists concerning the efficacy of web-based social norms interventions to decrease alcohol consumption in students. In the field of smoking cessation, Internet interventions are much more heterogeneous concerning the target group and the provided interventions. So far, 5 controlled studies concerning Internet interventions for smoking cessation in adolescents are available, 2 of these studies were effective in decreasing the smoking prevalence at the last follow-up. Interventions using mobile phone text messaging for smoking cessation were well accepted and promising; however, they were primarily tested within pilot studies and conclusions about their efficacy are not possible so far. CONCLUSION: Suggestions for the implementation of certain intervention approaches in Germany could not be derived from the existing studies. For research in Germany, it is suggested to work on the following topics: (1) testing the efficacy of web-based social norms interventions to decrease alcohol consumption in student and non-student samples, (2) testing the efficacy of Internet interventions for smoking cessation, and (3) testing the efficacy of text messaging interventions for smoking cessation.

Immunochemotherapy with rituximab, methotrexate, procarbazine, and lomustine for primary CNS lymphoma (PCNSL) in the elderly.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma confined to the central nervous system. In this article, we report the results of a pilot trial adding rituximab to the established regimen consisting of methotrexate, procarbazine, and lomustine (R-MCP). DESIGN AND METHODS: PCNSL patients ≥65 years without Karnofsky performance score (KPS) limit were included. R-MCP regimen consisted of rituximab (375 mg/m(2) i.v. on days -6, 1, 15, and 29), methotrexate (3 g/m(2) i.v., days 2, 16, and 30) followed by folinic rescue, procarbazine (60 mg/m(2) orally, days 2-11), and lomustine (110 mg/m(2) orally, day 2). A maximum of three 43-day cycles were applied. Primary end point was response to treatment obtained by magnetic resonance imaging. Secondary end points were overall survival (OS) and progression-free survival (PFS). RESULTS: Twenty-eight patients were included (median age 75, median KPS 60%). Best documented response: complete remission in 18 of 28 (64%), partial remission in 5 of 28 (18%), stable disease in 1 of 28 (4%), and progressive disease in 2 of 28 (7%) patients. Response was not assessed in two patients. Two treatment-associated deaths were observed. After a median follow-up of 36 months, the 3-year PFS and OS was 31%. CONCLUSION: R-MCP regimen is well tolerated and active in elderly patients with newly diagnosed PCNSL.

Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial.

BACKGROUND: B-type CpG oligodeoxynucleotides (ODN) is currently used in clinical trials because of its prolonged half-life, which is due to its phosphorothioate backbone. A-type CpG ODN is a stronger inducer of IFN but has an unstable phosphodiester backbone that has so far prohibited its clinical use. However, upon association with virus-like particles (VLP) consisting of the bacteriophage Qbeta coat protein, A-type CpG ODN can be stabilized and can become an efficient adjuvant in mice. Therefore, the phase I/IIa study presented represents the first test of A-type CpGs in humans. OBJECTIVE: To test the safety, tolerability and clinical efficacy of QbG10 as an adjuvant for subcutaneous immunotherapy with a house dust mite (HDM) allergen extract in allergic patients. METHODS: A single centre, open-label phase I/IIa study evaluated the safety, tolerability and clinical efficacy of QbG10 as an adjuvant to immunotherapy with a subcutaneous HMD allergen extract in 20 patients suffering from HDM allergy. Twenty-one patients were enrolled between March and July 2005. Individual immunotherapy lasted 10 weeks. Clinical end-points included questionnaires, conjunctival provocation, skin prick tests and the measurement of allergen-specific IgG and IgE. RESULTS: QbG10 was well tolerated. Almost complete tolerance to the allergen was observed in conjunctival provocation testing after treatment with QbG10, and symptoms of rhinitis and allergic asthma were significantly reduced. Within 10 weeks of therapy, patients were nearly symptom-free and this amelioration lasted for at least 38 weeks post-treatment. Following injections of QbG10 and HDM allergen extract, allergen-specific IgG increased, while there was a transient increase in allergen-specific IgE titres. Skin reactivity to HDM was reduced. CONCLUSION: The subcutaneous application of HDM allergen, together with A-type CpG ODN packaged into VLP, was safe. All patients achieved practically complete alleviation of allergy symptoms after 10 weeks of immunotherapy. This promising clinical outcome calls for larger placebo-controlled phase II studies.

Activity of antibiotics against Fusarium and Aspergillus.

BACKGROUND/AIMS: To study the susceptibility of Fusarium and Aspergillus isolated from keratitis to amoxicillin, cefazolin, chloramphenicol, moxifloxacin, tobramycin and benzalkonium chloride (BAK). METHODS: 10 isolates of Fusarium and 10 isolates of Aspergillus from cases of fungal keratitis at Aravind Eye Hospital in South India were tested using microbroth dilution for susceptibility to amoxicillin, cefazolin, chloramphenicol, moxifloxacin, tobramycin and BAK. The minimum inhibitory concentration (MIC) median and 90th percentile were determined. RESULTS: BAK had the lowest MIC for both Fusarium and Aspergillus. Chloramphenicol had activity against both Fusarium and Aspergillus, while moxifloxacin and tobramycin had activity against Fusarium but not Aspergillus. CONCLUSIONS: The susceptibility of Fusarium to tobramycin, moxifloxacin, chloramphenicol and BAK and of Aspergillus to chloramphenicol and BAK may explain anecdotal reports of fungal ulcers that improved with antibiotic treatment alone. While some of the MICs of antibiotics and BAK are lower than the typically prescribed concentrations, they are not in the range of antifungal agents such as voriconazole, natamycin and amphotericin B. Antibiotics may, however, have a modest effect on Fusarium and Aspergillus when used as initial treatment prior to identification of the pathological organism.

[Continuous individual support of smoking cessation in socially deprived young adults via mobile phones--results of a pilot study]. / Kontinuierliche individuelle Förderung der Rauchabstinenz bei sozial benachteiligten jungen Erwachsenen über das Handy--Ergebnisse einer Pilotstudie.

OBJECTIVE: The aim of this study was to test the feasibility and acceptability of an intervention using text messaging (SMS) for continuous, individual support of smoking cessation. METHODS: Ninety-three socially deprived young adults were screened for smoking status and usage of text messaging in an institution for occupational rehabilitation. People who reported smoking daily and using text messaging at least weekly were invited to participate in a 12-week, SMS-based intervention. Individualised SMS-feedbacks were sent to the participants weekly, based on data from the baseline assessment and the weekly SMS assessment of the intention to quit smoking. Additionally, the participants could request SMS support whenever they suffered from withdrawal symptoms or craving. The intervention was based on the transtheoretical model of behaviour change (TTM). All of the 35 persons who met the inclusion criteria for the study registered for study participation; post-assessments were obtained from 33 participants. RESULTS: The average participant answered 8 of the 12 weekly SMS questions. The SMS-based questions and -feedbacks were evaluated as self-explanatory by the participants. At post-assessment, five participants (15%) reported occasional instead of daily smoking. None of the participants reported abstinence after the intervention. Pre-post comparisons revealed a reduction in the number of cigarettes smoked per day as well as in the heaviness of smoking and an increase in risk perception. No significant differences were found for situational urge to smoke and intention to change. CONCLUSION: The intervention proved to be feasible in a sample of socially deprived young adults, and was well accepted. The first results concerning its effectiveness are promising. The examination of this approach within a controlled study seems reasonable.

[Diversity and accessibility of smoking cessation aids in the internet]. / Vielfalt und Auffindbarkeit von Hilfeangeboten zur Raucherentwöhnung im Internet.

AIM OF THE STUDY: Only a few smokers use smoking cessation aids. The Internet can act as a medium to improve the dissemination of traditional smoking cessation aids, but can also provide direct help by its own interactive capabilities. The purpose of this study is to give an overview of the different smoking cessation aids offered via the Internet and to categorise their contents. METHODS: Two different search strategies were used to find smoking cessation aids on the Internet. The first was a search with the search engine Google. Six search terms were previously generated by interviews with one hundred smokers. Using these terms, the Google search resulted in a list of 106 websites. The second strategy was a direct search on 31 websites of different health-related institutions. To classify the smoking cessation aids on the websites, a system of different categories was developed. RESULTS: The offers for smoking cessation on the Internet could be assigned to 11 categories. General information about smoking cessation was the most and interactive programs was the least represented category. The websites of the health-related institutions offered a larger variety of directly useable smoking cessation aids (39%) than the websites retrieved via Google (29%). CONCLUSION: Interactive smoking cessation aids which provide individual support are still underrepresented on the Internet. Direct search strategies on the pages of health-related institutions were more promising than the use of a search engine. The proactive promotion of quality-controlled Internet offers seems to be important to capitalise on the potential of the Internet.

Sympathectomy decreases size and invasiveness of tongue cancer in rats.

The sympathetic nervous system plays a role in carcinogenesis wherein locally released sympathetic neurotransmitters affect proliferation, angiogenesis, vessel permeability, lymphocyte traffic and cytokine production. The present in vivo study was designed to investigate whether surgical sympathectomy, both unilateral and bilateral, had an effect on tumor growth, interstitial fluid pressure (IFP) and lymphatics in rat tongue cancer. We used 4-nitroquinoline-1-oxide (4-NQO) in drinking water for 19 weeks to induce tongue cancer in 20 Dark Agouti rats. After 11 weeks, one group underwent unilateral sympathectomy and another underwent bilateral sympathectomy, while the third group underwent sham surgery. By 19 weeks, tumors in the bilaterally sympathectomized (BL-SCGx) rats were significantly smaller (P<0.05), more diffuse in appearance and less invasive (P<0.05) compared with the large exophytic tumors in the sham-operated rats. The relative lymphatic area was significantly decreased (P<0.05) in tumors in the BL-SCGx rats compared with the sham group. Interestingly, the tumors in rats that underwent unilateral or bilateral sympathectomy had a significantly lower (P<0.05) IFP than those in sham rats. Lack of tyrosine hydroxylase (TH) immunoreactive nerves and few neuropeptide Y (NPY) positive fibers indicate absence of sympathetic nerve fibers in the bilateral sympathectomized group. The peritumoral lymph vessel area was correlated with the tumor size (P<0.001), depth of invasion (P<0.001), weight of rats (P<0.005) and IFP (P<0.05). In conclusion, the present study presents evidence that deprivation of sympathetic nerves decreases tumor growth in rat tongue, probably caused by decreasing IFP and lymph vessel area.

[An internet connecting bridge between specialized institution and the daily routine]. / Neustart nach stationärer Psychotherapie.

The "Internet-Brücke" is intended to facilitate the patient's return from a specialist institution for psychotherapy and psychosomatics to the everyday setting. Participants meet once a week in an internet chat room. The open group sessions are accompanied by a group therapist, and their overall availability is limited to 12-15 weeks. This option was greatly welcomed by the patients, and from the technical point of view proved reliable, secure and easy to use. In a prospective, controlled study, the "Internet-Brücke" turned out to be an effective means of maintaining the health improvements achieved during institutionalized treatment.This option would appear to be strongly indicated when continued, post-institution treatment either cannot be provided at all, or only after too long a delay.

Coated textiles in the treatment of atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing prevalence over the last few decades. Various factors are known to aggravate the disease. In particular, wool and synthetic fabrics with harsh textile fibres, aggressive detergents and climatic factors may exacerbate AD. Cutaneous superinfection, particularly with Staphylococcus aureus, is also recognized as an important factor in the elicitation and maintenance of skin inflammation and acute exacerbations of AD. The severity of AD correlates with S. aureus colonization of the skin. Beside the treatment of AD patients with creams and emollients, new developments in the textile industry may have therapeutic implications. Silk or silvercoated textiles show antimicrobial properties that can significantly reduce the burden of S. aureus, leading to a positive effect on AD. Silver products have been used as wound dressing, whereby silver has antiseptic properties, and drug resistance is hardly found. Padycare textiles consist of micromesh material containing woven silver filaments with a total silver content of 20%. In vitro studies of these silver-coated textiles demonstrated a significant decrease in S. aureus and Pseudomonas aeruginosa as well as Candida albicans. Silk has been increasingly implemented in medical treatment of AD thanks to its unique smoothness that reduces irritation. Silk can be coated with antimicrobials (Dermasilk). The combination of the smoothness of silk with an antimicrobial finish appears to make an ideal textile for patients suffering from AD.

Modulation of dental inflammation by the sympathetic nervous system.

Recent findings have indicated that immune responses are subjected to modulation by the sympathetic nervous system (SNS). Moreover, the findings show that the SNS inhibits the production of pro-inflammatory cytokines, while stimulating the production of anti-inflammatory cytokines. The present review is an attempt to summarize the current results on how the SNS affects inflammation in dental tissues. In dental tissues, it has been found that the SNS is significant for recruitment of inflammatory cells such as CD 43+ granulocytes. Sympathetic nerves appear to have an inhibitory effect on osteoclasts, odontoclasts, and on IL-1alpha production. The SNS stimulates reparative dentin production, since reparative dentin formation was reduced after sympathectomy. Sprouting of sympathetic nerve fibers occurs in chronically inflamed dental pulp, and neural imbalance caused by unilateral sympathectomy recruits immunoglobulin-producing cells to the dental pulp. In conclusion, this article presents evidence in support of interactions between the sympathetic nervous system and dental inflammation.

Restoration of fatty aldehyde dehydrogenase deficiency in Sjögren-Larsson syndrome.

Sjögren-Larsson syndrome (SLS) is an autosomal recessive neurocutaneous disorder caused by mutation in the ALDH3A2 gene that codes for human fatty aldehyde dehydrogenase (FALDH). Sjögren-Larsson syndrome patients lack FALDH, which catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acids. The impaired FALDH activity leads to congenital ichthyosis, mental retardation and spasticity. The current lack of treatment is an impetus to develop gene therapy strategies by introducing functional FALDH into defective cells. We delivered human FALDH into keratinocytes of SLS patients using recombinant adeno-associated virus-2 vectors. Transduction of SLS keratinocytes resulted in an augmentation of FALDH activity comparable to phenotypically normal heterozygous carriers. Toxicity of long-chain aldehydes for FALDH-deficient cells decreased almost to the level of unaffected keratinocytes. Three-dimensional culture of corrected SLS keratinocytes revealed an ameliorated FALDH expression. These studies demonstrate the restoration of FALDH in human SLS cells supporting the concept of gene therapy as a potential future treatment option for SLS.