[Procedures of complementary medicine in rheumatology]. / Komplementärmedizinische Verfahren in der Rheumatologie.

Patients with diseases of the musculoskeletal system are confronted with a large quantity of treatment offers based on methods of complementary medicine. Despite a considerable number of publications on this topic, the scientific evidence is still poor. This article focuses on Ayurvedic medicine (AM), traditional Chinese medicine (TCM), mind-body medicine and homeopathy. These procedures have a longstanding tradition of practice and each claims to have its own theoretical concept; however, the application in the field of rheumatology can only be recommended either for specific entities or, in the case of homeopathy, not at all. In addition, this article summarizes the evidence for dietary recommendations, nutritional supplements and herbal medicine in rheumatology. The latter topics are frequently discussed in the popular press and are a much-debated issue between physicians and patients; however, clear-cut recommendations for the application on a scientific basis are the exception and mainly consist of the endorsement to adhere to the principles of a Mediterranean diet.

[What is the potential of ChatGPT for qualified patient information? : Attempt of a structured analysis on the basis of a survey regarding complementary and alternative medicine (CAM) in rheumatology]. / Welches Potential hat ChatGPT 3.5 für eine qualifizierte Patienteninformation? : Versuch einer systematischen Analyse anhand einer Befragung zu komplementärmedizinischen Verfahren in der Rheumatologie.

INTRODUCTION: The chatbot ChatGPT represents a milestone in the interaction between humans and large databases that are accessible via the internet. It facilitates the answering of complex questions by enabling a communication in everyday language. Therefore, it is a potential source of information for those who are affected by rheumatic diseases. The aim of our investigation was to find out whether ChatGPT (version 3.5) is capable of giving qualified answers regarding the application of specific methods of complementary and alternative medicine (CAM) in three rheumatic diseases: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and granulomatosis with polyangiitis (GPA). In addition, it was investigated how the answers of the chatbot were influenced by the wording of the question. METHODS: The questioning of ChatGPT was performed in three parts. Part A consisted of an open question regarding the best way of treatment of the respective disease. In part B, the questions were directed towards possible indications for the application of CAM in general in one of the three disorders. In part C, the chatbot was asked for specific recommendations regarding one of three CAM methods: homeopathy, ayurvedic medicine and herbal medicine. Questions in parts B and C were expressed in two modifications: firstly, it was asked whether the specific CAM was applicable at all in certain rheumatic diseases. The second question asked which procedure of the respective CAM method worked best in the specific disease. The validity of the answers was checked by using the ChatGPT reliability score, a Likert scale ranging from 1 (lowest validity) to 7 (highest validity). RESULTS: The answers to the open questions of part A had the highest validity. In parts B and C, ChatGPT suggested a variety of CAM applications that lacked scientific evidence. The validity of the answers depended on the wording of the questions. If the question suggested the inclination to apply a certain CAM, the answers often lacked the information of missing evidence and were graded with lower score values. CONCLUSION: The answers of ChatGPT (version 3.5) regarding the applicability of CAM in selected rheumatic diseases are not convincingly based on scientific evidence. In addition, the wording of the questions affects the validity of the information. Currently, an uncritical application of ChatGPT as an instrument for patient information cannot be recommended.

[Therapeutic Pathways in Sarcoidosis. A Position Paper of the German Society of Respiratory Medicine (DGP)]. / Therapie der Sarkoidose. Ein Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin (DGP).

The present recommendations on the therapy of sarcoidosis of the German Respiratory Society (DGP) was written in 2023 as a German-language supplement and update of the international guidelines of the European Respiratory Society (ERS) from 2021. It contains 5 PICO questions (Patients, Intervention, Comparison, Outcomes) agreed in the consensus process, which are explained in the background text of the four articles: Confirmation of diagnosis and monitoring of the disease under therapy, general therapy recommendations, therapy of cutaneous sarcoidosis, therapy of cardiac sarcoidosis.

[Recommendations of the committee on complementary medicine and nutrition in ayurvedic medicine, homeopathy, nutrition and Mediterranean diet]. / Empfehlungen der Kommission Komplementäre Heilverfahren und Ernährung zu ayurvedischer Medizin, Homöopathie, Ernährung und mediterraner Kost.

Methods of complementary and alternative medicine (CAM) are appealing for many patients with rheumatic diseases. The scientific data are currently characterized by a large number of publications that stand in contrast to a remarkable shortage of valid clinical studies. The applications of CAM procedures are situated in an area of conflict between efforts for an evidence-based medicine and high-quality therapeutic concepts on the one hand and ill-founded or even dubious offers on the other hand. In 2021 the German Society of Rheumatology (DGRh) launched a committee for CAM and nutrition, which aims to collect and to evaluate the current evidence for CAM applications and nutritional medical interventions in rheumatology, in order to elaborate recommendations for the clinical practice. The current article presents recommendations for nutritional interventions in the rheumatological routine for four areas: nutrition, Mediterranean diet, ayurvedic medicine and homeopathy.

Controlling line defects in wrinkling: a pathway towards hierarchical wrinkling structures.

We demonstrate a novel approach for controlling the line defect formation in microscopic wrinkling structures by patterned plasma treatment of elastomeric surfaces. Wrinkles were formed on polydimethylsiloxane (PDMS) surfaces exposed to low-pressure plasma under uniaxial stretching and subsequent relaxation. The wrinkling wavelength λ can be regulated via the treatment time and choice of plasma process gases (H2, N2). Sequential masking allows for changing these parameters on micron-scale dimensions. Thus, abrupt changes of the wrinkling wavelength become feasible and result in line defects located at the boundary zone between areas of different wavelengths. Wavelengths, morphology, and mechanical properties of the respective areas are investigated by Atomic Force Microscopy and agree quantitatively with predictions of analytical models for wrinkle formation. Notably, the approach allows for the first time the realization of a dramatic wavelength change up to a factor of 7 to control the location of the branching zone. This allows structures with a fixed but also with a strictly alternating branching behavior. The morphology inside the branching zone is compared with finite element methods and shows semi-quantitative agreement. Thus our finding opens new perspectives for "programming" hierarchical wrinkling patterns with potential applications in optics, tribology, and biomimetic structuring of surfaces.

Capillary microscopy in Europeans with idiopathic Moyamoya angiopathy.

OBJECTIVE: In Europe, MMA is a very rare non-inflammatory vasculopathy. MMA is an important differential diagnosis of cerebral vasculitis. Systemic manifestations, such as livedo racemosa or renal artery stenosis, associated with Moyamoya variants suggest the involvement also of non-cerebral vessels. Hypothetically, capillary microscopy could be a promising non-invasive screening method to visualize microcirculation, for example prior to cerebral angiography. METHODS: Standardized capillary microscopic images were taken in European patients with MMA and subsequently evaluated in a blinded analysis, using data obtained from a large NP cohort and a large SLE cohort by the same blinded Investigator as controls. RESULTS: Twenty-four European MMD patients and 14 healthy accompanying controls were included in this study. The results were compared to 116 SLE patients and 754 NP subjects. In MMD patients, no capillary morphological differences were found in comparison with NP, in particular no density reduction or increased neoangiogenesis. The pattern observed in the SLE cohort was clearly distinct from NP and MMD with regard to vascular density, vascular damage, and neoangiogenesis. CONCLUSIONS: MMD is not associated with microvascular changes of the nailfold capillaries. In this respect, it is clearly distinct from SLE.

[Frequencies of musculoskeletal symptoms and disorders in the population-based German National Cohort (GNC)]. / Häufigkeiten muskuloskelettaler Symptome und Erkrankungen in der bevölkerungsbezogenen NAKO Gesundheitsstudie.

BACKGROUND: Musculoskeletal diseases and symptoms are very common in the general population. They lead to high healthcare costs and pose a significant burden to the national economy. OBJECTIVES: Based on data from the population-based German National Cohort (GNC), frequencies of musculoskeletal symptoms and diseases are reported, including back pain, osteoporosis, osteoarthritis, and arthritis. MATERIALS AND METHODS: Data were collected from March 2014 to March 2017 in adults aged 20-75 years during the first half of the baseline survey of the GNC. The sample comprised 101,779 interviewed subjects, including 9370 subjects who underwent clinical musculoskeletal examinations. The interview included questions about specific musculoskeletal disorders. A clinical examination of the hand provided information about palpable swollen joints and pressure-sensitive joints. Resting pain of the knees and hips was also assessed by a clinical examination. Frequencies were standardized to the German standard population of the year 2011. RESULTS: Having ever been diagnosed with recurrent back pain (22.5%) or osteoarthritis (20.6%) were the most common complaints reported in the interview; osteoporosis (2.9%) and rheumatoid arthritis (1.9%) were stated more seldom. According to the hand examination, 6.0% of all participants experienced pain in at least one finger joint. Resting pain was present in at least one knee among 8.2% and in at least one hip among 5.1% of the participants as assessed during the clinical examination. Women were more likely to report musculoskeletal disorders and symptoms than men. The proportion of adults affected by musculoskeletal diseases increased strongly with age. CONCLUSION: Musculoskeletal disorders and symptoms occur frequently. The burden of complaints and diagnoses is comparable to previous population-based surveys.

Nailfold capillaroscopy microscopy - an interdisciplinary appraisal.

Nailfold capillaroscopy is a method of great diagnostic value in the differential diagnosis of primary versus secondary Raynaud´s phenomenon, of systemic sclerosis versus other so called connective tissue diseases and of additional diagnostic value in other entities. Rheumatologists, dermatologists, and angiologists in Germany have convened in an interdisciplinary working group in which they synergistically combined their expertise to develop a common nomenclature and standards for the technical performance of nailfold capillary microscopy. The article gives an overview of historical and technical aspects of capillaroscopy, morphologic findings, and disease-specific patterns. It also provides a critical appraisal of its significance in the diagnosis and sequelae of these interdisciplinarily-managed diseases including its performance in children and gives an excursion in the potential perspectives of capillaroscopy in less common indications.

Validation and evaluation of the German version of the Systemic Lupus Activity Questionnaire (SLAQ).

OBJECTIVES: Disease activity accounts for damage, overall mortality and co-morbidities in SLE and should frequently be assessed to adapt therapeutic patient management. The Systemic Lupus Activity Questionnaire (SLAQ) is a patient-reported instrument for the assessment of disease activity derived from the Systemic Lupus Erythematosus Activity Measure (SLAM) and was originally developed in English. Our aim was to validate the SLAQ in German and evaluate its use in a large cohort. METHODS: We translated and adapted the SLAQ questionnaire in German. It was applied to SLE outpatients at a tertiary centre (n=328) and compared to the SLAMnolab and other SLE outcome parameters. Internal consistency, criterion validity, inter-rater and test-retest reliability as well as construct validity were examined. Correlation, Cronbach's alpha, Mann-Whitney U-test or the Kruskal-Wallis one-way analysis of variance test were ascertained where appropriate. Levels of statistical significance were defined at 5% (p<0.05). All reported p-values are two-tailed. RESULTS: The German SLAQ showed a comparable strong correlation with the SLAMnolab (r=0.632, p<0.0001) as the original version of the SLAQ and presented a good to excellent internal consistency reliability (Cronbach's alpha=0.89). Accrued damage as well as low disease activity are factors possibly influencing the score. Amongst others, scores were higher in patients with more reported flares, lower self-reported overall health, lower functional status and higher daily doses of prednisolone. CONCLUSIONS: Our German version of the SLAQ shows a comparable validity as the original SLAQ and is a promising instrument to survey disease activity in clinical routine as well as in clinical and epidemiological studies. Possible interacting factors need to be considered when applying.

Kinetically controlled metal-elastomer nanophases for environmentally resilient stretchable electronics.

Nanophase mixtures, leveraging the complementary strengths of each component, are vital for composites to overcome limitations posed by single elemental materials. Among these, metal-elastomer nanophases are particularly important, holding various practical applications for stretchable electronics. However, the methodology and understanding of nanophase mixing metals and elastomers are limited due to difficulties in blending caused by thermodynamic incompatibility. Here, we present a controlled method using kinetics to mix metal atoms with elastomeric chains on the nanoscale. We find that the chain migration flux and metal deposition rate are key factors, allowing the formation of reticular nanophases when kinetically in-phase. Moreover, we observe spontaneous structural evolution, resulting in gyrified structures akin to the human brain. The hybridized gyrified reticular nanophases exhibit strain-invariant metallic electrical conductivity up to 156% areal strain, unparalleled durability in organic solvents and aqueous environments with pH 2-13, and high mechanical robustness, a prerequisite for environmentally resilient devices.

High Frequency of Osteophytes Detected by High-Resolution Ultrasound at the Finger Joints of Asymptomatic Factory Workers.

Hand Osteoarthritis (HOA) is a frequently occurring musculoskeletal disease that impacts health. Diagnostic criteria often incorporate osteophytes documented through imaging procedures. Radiographic imaging is considered the gold standard; however, more sensitive and safer methods like ultrasound imaging are becoming increasingly important. We conducted a population-based cross-sectional study to examine the prevalence, grade, and pattern of osteophytes using high-resolution ultrasound investigation. Factory workers were recruited on-site for the study. Each participant had 26 finger joints examined using ultrasonography to grade the occurrence of osteophytes on a semi-quantitative scale ranging from 0-3, where higher scores indicate larger osteophytes. A total of 427 participants (mean age 53.5 years, range 20-79 years) were included, resulting in 11,000 joints scored. At least one osteophyte was found in 4546 out of 11,000 (41.3%) joints or in 426 out of 427 (99.8%) participants, but only 5.0% (553) of the joints showed grade 2 or 3 osteophytes. The total osteophyte sum score increased by 0.18 per year as age increased (p < 0.001). The distal interphalangeal joints were the most commonly affected, with 61%, followed by the proximal interphalangeal joints with 48%, carpometacarpal joint 1 with 39%, and metacarpophalangeal joints with 16%. There was no observed impact of gender or workload. In conclusion, ultrasound imaging proves to be a practical screening tool for osteophytes and HOA. Grade 1 osteophytes are often detected in the working population through ultrasound assessments and their incidence increases with age. The occurrence of grade 2 or 3 osteophytes is less frequent and indicates the clinical presence of HOA. Subsequent evaluations are imperative to ascertain the predictive significance of early osteophytes.

Proof-of-Concept Double-Blind Placebo-Controlled Trial Measuring Cartilage Composition in Early Rheumatoid Arthritis under TNF-α-Inhibitor Therapy.

Low levels of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) values are indicative of cartilage degeneration. Patients with early rheumatoid arthritis are known to have low dGEMRIC values due to inflammatory activity. The additional effect of biological disease-modifying antirheumatic drug (bDMARD) and conventional synthetic disease-modifying antirheumatic drug (csDMARD) treatment on cartilage status is still unclear. In this prospective, double-blinded, randomized proof-of-concept clinical trial, patients with early rheumatoid arthritis (disease duration less than 12 months from symptoms onset) were treated with methotrexate + adalimumab (10 patients: 6/4 (f/m)). A control group with methotrexate alone (four patients: 2/2 (f/m)) was used. Cartilage integrity in the metacarpophalangeal joints was compared using dGEMRIC at baseline, 12, and 24 weeks after treatment initiation. A statistically significant increase in dGEMRIC levels was found in the adalimumab group considering the results after 12 and 24 weeks of therapy (p < 0.05) but not in the control group (p: non-significant). After 24 weeks, a tendency towards increased dGEMRIC values under combination therapy was observed, whereas methotrexate alone showed a slight decrease without meeting the criteria of significance (dGEMRIC mean change: +85.8 ms [-156.2-+346.5 ms] vs. 30.75 ms [-273.0-+131.0 ms]; p: non-significant). After 24 weeks of treatment with a combination of methotrexate and adalimumab, a trend indicating improvement in cartilage composition is seen in patients with early rheumatoid arthritis. However, treatment with methotrexate alone showed no change in cartilage composition, as observed in dGEMRIC sequences of metacarpophalangeal joints.

Determinants of patient and physician global assessments of disease activity in anti-neutrophil cytoplasmic antibody-associated vasculitis.

Objective: To compare physician and patient assessments of global disease activity in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and to identify associated factors. Methods: Global disease activity scores (0-10 points) were retrospectively analyzed from physicians and patients with AAV at each outpatient visit from 2010 to 2020. We compared the scores and performed a linear regression with a random effects to identify associated factors. Results: Patients (n = 143, 1,291 pairs, 52% female) had a mean 64 (±15) years of age and a mean disease duration of 9 (±7) years. Patients and physicians global disease activity assessments showed a moderate correlation (Pearson R 0.31, CI [0.23-0.52], p < 0.001). Linear regression showed a strong association between the physician-documented disease activity scores and serum CRP levels (ß = 0.22, CI [0.18, 0.28]), disease duration (ß = -0.022, CI [-0.04,-0.01]) and patients' assessment of disease activity (ß = 0.08, CI [0.04, 0.12]). By contrast, patient assessments were strongly associated with the degree of pain (ß = 0.30, CI [0.25, 0.35]), functional limitations in daily living (HAQ, ß = 0.49, CI [0.21, 0.78]) and the global physical well-being (NRS, ß = 0.39, CI [0.32, 0.46]). Conclusion: Patients' and physicians' assessments of disease activity correlated. High CRP levels and disease duration were associated with physician-assessed disease activity scores, while subjective limitations were associated with higher patient-assessed disease activity scores. These findings highlight and support the need to develop and evaluate patient-reported outcomes to assess disease activity in patients diagnosed with AAV.

Paradoxical Reactions to Biologicals in Chronic Inflammatory Systemic Diseases.

BACKGROUND: Biological agents that contain substances affecting the immune system are increasingly being used to treat chronic inflammatory systemic diseases. Aside from the expected adverse effects, they can also induce unexpected paradoxical reactions (PR). A reaction is called paradoxical when a substance that is generally therapeutically effective induces the opposite of what is intended, with the new appearance or exacerbation of inflammatory changes in the skin and other organs. METHODS: The paradoxical reactions that have been described since 1997 are presented here on the basis of the available literature on the main types of chronic inflammatory systemic disease, which was retrieved by a selective search in the PubMed and Google Scholar databases. RESULTS: Many studies and registers to date contain no mention of paradoxical reactions. Anti-TNF-alpha treatment for patients with ankylosing spondylitis leads to paradoxical reactions in 19 per 1000 patient years, compared to 11 per 1000 patient years with conventional treatment; the corresponding frequency for paradoxical psoriasis in patients with other chronic inflammatory systemic diseases are 1.04-3.68 versus 1.45 per 1000 patient years. Paradoxical reactions tend to be more common with anti-TNF-alpha treatment than, for example, with the administration of ustekinumab, vedolizumab, and other agents. It is unclear whether some drugs have been noted to cause PR more commonly than others because of varying times since their approval, differences in immunogenicity, and differences between their target structures. CONCLUSION: Paradoxical reactions induced by biological agents are a problem confronting physicians in multiple specialties. They need to be distinguished from infectious and neoplastic diseases and from autoimmune conditions of other types. The treatment options for paradoxical reactions include local treatment, symptomatic therapy, prednisolone administration, and the discontinuation or switching of the biological agent, although some patients will react with a further paradoxical reaction to a different biological agent that is used instead.

[Functional vascular acrosyndromes]. / Funktionelle akrale Durchblutungsstörungen.

Vascular acrosyndromes are characterized by sparse, uniform clinical manifestations and a variety of possible pathomechanisms. The present article focuses on the functional entities. Raynaud phenomenon is based on cold- or stress-induced vasospasms of acral arteries. It is defined by the color changes of the skin, in the typical case white-blue-red (tricolore). The long fingers are most commonly affected. The etiology is unknown, and the pathophysiology is poorly understood. A distinction is made between primary and a secondary Raynaud phenomenon. The most important underlying diseases include collagenosis, primarily systemic sclerosis, and malignancies; furthermore, medications and drugs may promote vasospasm. Treatment is aimed at preventing or breaking the vasospasm, but has been only partially effective in doing so. Acrocyanosis is a vasospastic dystonic acral disorder that results in permanent reddish-livid discoloration, especially of the hands and feet. Secondary forms occur in collagenosis, malignancies, and myelodysplastic syndromes. The etiology and pathophysiology are virtually unknown. Targeted pharmacological intervention is not possible. Unlike all other vascular acrosyndromes, erythromelalgia is characterized by hyperemia. The primary form is a genetic sodium channelopathy, while secondary forms include malignancies, connective tissue diseases, and myelodysplastic syndromes. The symptoms are often distressing and disabling. Therapy requires a multimodal approach that includes both nonpharmacological and pharmacological strategies. Close interdisciplinary collaboration is essential for the management of this disease.

Musculoskeletal ultrasound as a screening-tool for rheumatoid arthritis: results of the "Rheuma-Truck" screening and awareness initiative.

OBJECTIVE: To evaluate musculoskeletal ultrasound (MSUS) as a screening tool for rheumatoid arthritis (RA) and osteoarthritis (OA) patients in a rheumatology-screening program. PATIENTS AND METHODS: To raise awareness for rheumatic diseases, a mobile rheumatology office was deployed in different cities of Germany ("Rheuma-Truck"). Standardized questionnaire assessment, testing for rheumatoid factor and citrullinated peptide antibodies and medical student driven MSUS of the clinically dominant hand/foot including wrist, MCP-II, -III, -V, PIP-II, -III, MTP-II and -V were offered free of charge to the population. In case of suspicious results, a rheumatologist was consulted. RESULTS: In MSUS, 192 of 560 selected volunteers (aged 18-89, mean 52.7 years; 72.9% female) had suspicious findings including synovitis or erosions primarily affecting the MTP-II (11.8%), dorsal wrist (8.9%), and MCP-II (7%). 354 of the 560 volunteers further visited a rheumatologist of whom 76 were diagnosed with RA. According to the 'US7 Score', a sum scores ≥ 5 was significantly predictive for RA (odds ratio (OR) 5.06; confidence interval (CI) 0.83-35.32). 313 volunteers displayed signs of OA including osteophytes, while MCP-II (36.2%), MCP-III (14.8%), and the wrist (10.5%) were mostly affected. Diagnosis of RA was favoured over OA if the wrist (OR 4.2; CI 1.28-13.95), MTP-II (OR 1.62; CI 1.0-2.6), and MCP-V (OR 2.0; CI 1.0-3.8) were involved. CONCLUSION: Medical student driven MSUS by the 'US7 Score' can facilitate diagnosis of RA in rheumatology-screening programs due to the level of the score and the affected joints. A high rate of unknown OA signs was detected by MSUS. A mobile rheumatology office displays an opportunity to screen patients for RA and OA.

Permutation importance: a corrected feature importance measure.

MOTIVATION: In life sciences, interpretability of machine learning models is as important as their prediction accuracy. Linear models are probably the most frequently used methods for assessing feature relevance, despite their relative inflexibility. However, in the past years effective estimators of feature relevance have been derived for highly complex or non-parametric models such as support vector machines and RandomForest (RF) models. Recently, it has been observed that RF models are biased in such a way that categorical variables with a large number of categories are preferred. RESULTS: In this work, we introduce a heuristic for normalizing feature importance measures that can correct the feature importance bias. The method is based on repeated permutations of the outcome vector for estimating the distribution of measured importance for each variable in a non-informative setting. The P-value of the observed importance provides a corrected measure of feature importance. We apply our method to simulated data and demonstrate that (i) non-informative predictors do not receive significant P-values, (ii) informative variables can successfully be recovered among non-informative variables and (iii) P-values computed with permutation importance (PIMP) are very helpful for deciding the significance of variables, and therefore improve model interpretability. Furthermore, PIMP was used to correct RF-based importance measures for two real-world case studies. We propose an improved RF model that uses the significant variables with respect to the PIMP measure and show that its prediction accuracy is superior to that of other existing models. AVAILABILITY: R code for the method presented in this article is available at http://www.mpi-inf.mpg.de/ approximately altmann/download/PIMP.R CONTACT: altmann@mpi-inf.mpg.de, laura.tolosi@mpi-inf.mpg.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Community screening and treatment of asymptomatic carriers of Plasmodium falciparum with artemether-lumefantrine to reduce malaria disease burden: a modelling and simulation analysis.

BACKGROUND: Asymptomatic carriers of Plasmodium falciparum serve as a reservoir of parasites for malaria transmission. Identification and treatment of asymptomatic carriers within a region may reduce the parasite reservoir and influence malaria transmission in that area. METHODS: Using computer simulation, this analysis explored the impact of community screening campaigns (CSC) followed by systematic treatment of P. falciparum asymptomatic carriers (AC) with artemether-lumefantrine (AL) on disease transmission. The model created by Okell et al (originally designed to explore the impact of the introduction of treatment with artemisinin-based combination therapy on malaria endemicity) was modified to represent CSC and treatment of AC with AL, with the addition of malaria vector seasonality. The age grouping, relative distribution of age in a region, and degree of heterogeneity in disease transmission were maintained. The number and frequency of CSC and their relative timing were explored in terms of their effect on malaria incidence. A sensitivity analysis was conducted to determine the factors with the greatest impact on the model predictions. RESULTS: The simulation showed that the intervention that had the largest effect was performed in an area with high endemicity (entomological inoculation rate, EIR > 200); however, the rate of infection returned to its normal level in the subsequent year, unless the intervention was repeated. In areas with low disease burden (EIR < 10), the reduction was sustained for over three years after a single intervention. Three CSC scheduled in close succession (monthly intervals) at the start of the dry season had the greatest impact on the success of the intervention. CONCLUSIONS: Community screening and treatment of asymptomatic carriers with AL may reduce malaria transmission significantly. The initial level of disease intensity has the greatest impact on the potential magnitude and duration of malaria reduction. When combined with other interventions (e.g. long-lasting insecticide-treated nets, rapid diagnostic tests, prompt diagnosis and treatment, and, where appropriate, indoor residual spraying) the effect of this intervention can be sustained for many years, and it could become a tool to accelerate the reduction in transmission intensity to pre-elimination levels. Repeated interventions at least every other year may help to prolong the effect. The use of an effective diagnostic tool and a highly effective ACT, such as AL, is also vital. The modelling supports the evaluation of this approach in a prospective clinical trial to reduce the pool of infective vectors for malaria transmission in an area with marked seasonality.

Altered serum levels of human neutrophil peptides (HNP) and human beta-defensin 2 (hBD2) in Wegener's granulomatosis.

Defensins are highly conserved peptides with antimicrobial and immunomodulatory functions. Due to their chemotactic properties on mononuclear cells, including dendritic cells and macrophages, defensins may contribute to granuloma formation in Wegener's granulomatosis (WG). In order to explore whether these peptides might be involved in WG pathogenesis, sera of patients were screened to detect altered defensin levels. For this purpose, serum and EDTA-blood of patients with WG (n = 17; aged 54.8 ± 15.5 years) and age- and sex-matched healthy controls (n = 24; aged 55.5 ± 16.8 years) were collected. Levels of neutrophil α-defensins (human neutrophil peptides, HNP) and ß-defensin (hBD) 2 and 3 in serum were measured by ELISA. By this means, WG patients displayed higher serum levels of hBD2 and HNP when compared to controls. Furthermore, serum hBD2 was raised in patients with meningeal granulomas (n = 4) or in those undergoing treatment with cyclophosphamide (n = 4). In order to detect whether increased gene expression in polymorphonuclear cells is responsible for the elevated defensin levels, real-time polymerase chain reaction with gene-specific primers was performed. Expression of specific mRNA in polymorphonuclear cells was observed for HNP only, but did not parallel HNP serum levels, suggesting that degranulation rather than increased gene expression may be responsible for increased HNP serum levels in WG. In conclusion, elevated serum levels of HNP and hBD2 in WG patients suggest a role for both defensins in WG pathogenesis.