64 resultados para Sleeping sickness


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Little is known about the ocular and cerebral blood flow during exposure to increasingly hypoxic conditions at high altitudes. There is evidence that an increase in cerebral blood flow resulting from altered autoregulation constitutes a risk factor for acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) by leading to capillary overperfusion and vasogenic cerebral edema. The retina represents the only part of the central nervous system where capillary blood flow is visible and can be measured by noninvasive means. In this study we aimed to gain insights into retinal and choroidal autoregulatory properties during hypoxia and to correlate circulatory changes to symptoms of AMS and clinical signs of HACE. This observational study was performed within the scope of a high-altitude medical research expedition to Mount Muztagh Ata (7,546 m). Twenty seven participants underwent general and ophthalmic examinations up to a maximal height of 6,800 m. Examinations included fundus photography and measurements of retinal and choroidal blood flow, as well as measurement of arterial oxygen saturation and hematocrit. The initial increase in retinal blood velocity was followed by a decrease despite further ascent, whereas choroidal flow increase occurred later, at even higher altitudes. The sum of all adaptational mechanisms resulted in a stable oxygen delivery to the retina and the choroid. Parameters reflecting the retinal circulation and optic disc swelling correlated well with the occurrence of AMS-related symptoms. We demonstrate that sojourns at high altitudes trigger distinct behavior of retinal and choroidal blood flow. Increase in retinal but not in choroidal blood flow correlated with the occurrence of AMS-related symptoms.

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Depression and anxiety previously predicted coronary artery disease (CAD) risk. Inflammation contributes to CAD and shows an association with depression. We followed 57 teachers (mean 49+/-8 years) over 21 months and investigated whether changes in depressive and anxiety symptoms relate to those in the CAD risk and inflammation marker fibrinogen and vice versa. Increase in depressive symptoms and in fibrinogen levels were significantly correlated. While controlling for baseline depression rendered the association between changes in depression and fibrinogen nonsignificant, taking into account baseline fibrinogen levels maintained the predictive value of fibrinogen change for depression change. Anxiety and fibrinogen changes were not significantly correlated. This dynamic relationship between depression and the inflammatory biomarker fibrinogen might advance our knowledge about psychobiological mechanisms underlying both CAD and sickness behavior.

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OBJECTIVES Dentine hypersensitivity (DH) manifests as a transient but arresting oral pain. The incidence is thought to be rising, particularly in young adults, due to increases in consumption of healthy, yet erosive, diets. This study aimed to assess the prevalence of DH and relative importance of risk factors, in 18-35 year old Europeans. METHODS In 2011, 3187 adults were enrolled from general dental practices in France, Spain, Italy, United Kingdom, Finland, Latvia and Estonia. DH was clinically evaluated by cold air tooth stimulation, patient pain rating (yes/no), accompanied by investigator pain rating (Schiff 0-3). Erosive toothwear (BEWE index 0-3) and gingival recession (mm) were recorded. Patients completed a questionnaire regarding the nature of their DH, erosive dietary intake and toothbrushing habits. RESULTS 41.9% of patients reported pain on tooth stimulation and 56.8% scored ≥1 on Schiff scale for at least one tooth. Clinical elicited sensitivity was closely related to Schiff score and to a lesser degree, questionnaire reported sensitivity (26.8%), possibly reflecting the transient nature of the pain, alongside good coping mechanisms. Significant associations were found between clinically elicited DH and erosive toothwear and gingival recession. The questionnaire showed marked associations between DH and risk factors including heartburn/acid reflux, vomiting, sleeping medications, energy drinks, smoking and acid dietary intake. CONCLUSION Overall, the prevalence of DH was high compared to many published findings, with a strong, progressive relationship between DH and erosive toothwear, which is important to recognise for patient preventive therapies and clinical management of DH pain.

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BACKGROUND Acute exposure to high altitude stimulates free radical formation in lowlanders, yet whether this persists during chronic exposure in healthy, well-adapted and maladapted highlanders suffering from chronic mountain sickness (CMS) remains to be established. METHODS Oxidative-nitrosative stress (as determined by the presence of the biomarkers ascorbate radical [A •- ], via electron paramagnetic resonance spectroscopy, and nitrite [NO 2 2 ], via ozone-based chemiluminescence) was assessed in venous blood of 25 male highlanders in Bolivia living at 3,600 m with CMS (n 5 13, CMS 1 ) and without CMS (n 5 12, CMS 2 ). Twelve age- and activity-matched, healthy, male lowlanders were examined at sea level and during acute hypoxia. We also measured fl ow-mediated dilatation (FMD), arterial stiffness defined by augmentation index normalized for a heart rate of 75 beats/min (AIx-75), and carotid intima-media thickness (IMT). RESULTS Compared with normoxic lowlanders, oxidative-nitrosative stress was moderately increased in the CMS 2 group ( P , .05), as indicated by elevated A •- (3,191 457 arbitrary units [AU] vs 2,640 445 AU) and lower NO 2 2 (206 55 nM vs 420 128 nM), whereas vascular function remained preserved. This was comparable to that observed during acute hypoxia in lowlanders in whom vascular dysfunction is typically observed. In contrast, this response was markedly exaggerated in CMS 1 group (A •- , 3,765 429 AU; NO 2 2 , 148 50 nM) compared with both the CMS 2 group and lowlanders ( P , .05). This was associated with systemic vascular dysfunction as indicated by lower ( P , .05 vs CMS 2 ) FMD (4.2% 0.7% vs 7.6% 1.7%) and increased AIx-75 (23% 8% vs 12% 7%) and carotid IMT (714 127 m M vs 588 94 m M). CONCLUSIONS Healthy highlanders display a moderate, sustained elevation in oxidative-nitrosative stress that, unlike the equivalent increase evoked by acute hypoxia in healthy lowlanders, failed to affect vascular function. Its more marked elevation in patients with CMS may contribute to systemic vascular dysfunction.

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OBJECTIVE Measuring children's health-related quality of life (HRQOL) is of growing importance given increasing chronic diseases. By integrating HRQOL questions into the European GABRIEL study, we assessed differences in HRQOL between rural farm and non-farm children from Germany, Austria, Switzerland and Poland to relate it to common childhood health problems and to compare it to a representative, mostly urban German population sample (KIGGS). METHODS The parents of 10,400 school-aged children answered comprehensive questionnaires including health-related questions and the KINDL-R questions assessing HRQOL. RESULTS Austrian children reported highest KINDL-R scores (mean: 80.9; 95 % CI [80.4, 81.4]) and Polish children the lowest (74.5; [73.9, 75.0]). Farm children reported higher KINDL-R scores than non-farm children (p = 0.002). Significantly lower scores were observed in children with allergic diseases (p < 0.001), with sleeping difficulties (p < 0.001) and in overweight children (p = 0.04). The German GABRIEL sample reported higher mean scores (age 7-10 years: 80.1, [79.9, 80.4]; age 11-13 years: 77.1, [74.9, 79.2]) compared to the urban KIGGS study (age 7-10 years: 79.0, [78.7-79.3]; age 11-13 years: 75.1 [74.6-75.6]). Socio-demographic or health-related factors could not explain differences in HRQOL between countries. CONCLUSIONS Future increases in chronic diseases may negatively impact children's HRQOL.

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INTRODUCTION: Task stressors typically refer to characteristics such as not having enough time or resources, ambiguous demands, or the like. We suggest the perceived lack of legitimacy as an additional feature of tasks as a source of stress. Tasks are “illegitimate” to the extent that it is perceived as improper to expect employees to execute them – not because of difficulties in executing them, but because of their content for a given person, time, and situation; they are illegitimate because a) they are not conforming to a specific occupational role, as in “non-nursing activities” (called unreasonable) or b) there is no legitimate need for them to exist (called unnecessary; Semmer et al., 2007). These features make illegitimate tasks a unique task-related stressor. The concept of illegitimate tasks grew from the “Stress-as-Offense-to-Self” theory (SOS; Semmer et al, 2007); it is conceptually related to role stress (Kahn et al., 1964; Beehr & Glazer, 2005) and the organizational justice tradition (Cropanzano et al., 2001; Greenberg, 2010). SOS argues that a threat to one’s self-image is at the core of many stressful experiences. Violating role expectations, illegitimate tasks can be regarded as a special case of role conflict. As roles shape identities, this violation is postulated to constitute a threat to one’s professional identity. Being assigned a task considered illegitimate is likely to be considered unfair. Lack of fairness, in turn, contains a message about one’s social standing, and thus, the self. However, the aspects discussed have not received much attention in the role stress or the justice/fairness tradition. OBJECTIVE: Illegitimate tasks are a rather recent concept that has to be established as a construct in its own right by showing that it is associated with well-being/strain while controlling for other stressors, most notably role conflict and lack of justice. The aim of the presentation is to present the evidence accumulated so far. METHODS AND RESULTS: We present several studies employing different designs, using different control variables, and testing associations with different criteria. Study 1 demonstrates associations of illegitimate tasks with self-esteem, feelings of resentment against one’s organization, and burnout, controlling for distributive justice, role conflict, and social stressors (i.e. tensions). Study 2 yielded comparable results, using the same outcome variables but controlling for distributive as well as procedural / interactional justice. Study 3 demonstrated associations between illegitimate tasks and feelings of stress, sleeping problems, and emotional exhaustion, controlling for demands, control, and social support among medical doctors. Study 4 showed that feeling appreciated by one’s superior acted as a mediator between illegitimate tasks and job satisfaction and resentments towards the military in Swiss military officers. Study 5 demonstrated an association of illegitimate tasks with counterproductive work behavior (Semmer et al. 2010). Studies 1 to 5 were cross-sectional. In Study 6, illegitimate demands predicted irritability and resentments towards one’s organization longitudinally. Study 7 also was longitudinal, focusing on intra-individual variation in multilevel modeling; occasion-specific illegitimate tasks predicted cortisol among those who judged their health as comparatively poor. Studies 1-3 and 6 used SEM, and measurement models that used unreasonable and unnecessary tasks as indicators (isolated parceling) yielded a good fit. IMPLICATIONS & CONCLUSIONS: These studies demonstrate that illegitimate tasks are a stressor in its own right that is worth studying. It illuminates the social meaning of job design, emphasizing the implications of tasks for the (professional) self, and thus combining aspects that are traditionally treated as separate, that is, social aspects and task characteristics. Practical implications are that supervisors and managers should be alerted to the social messages that may be contained in task assignments (cf. Semmer & Beehr, in press).

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STUDY OBJECTIVES 1) To investigate the impact of acetazolamide, a drug commonly prescribed for altitude sickness, on cortical oscillations in patients with obstructive sleep apnea syndrome (OSAS). 2) To examine alterations in the sleep EEG after short-term discontinuation of continuous positive airway pressure (CPAP) therapy. DESIGN Data from two double-blind, placebo-controlled randomized cross-over design studies were analyzed. SETTING Polysomnographic recordings in sleep laboratory at 490 m and at moderate altitudes in the Swiss Alps: 1630 or 1860 m and 2590 m. PATIENTS Study 1: 39 OSAS patients. Study 2: 41 OSAS patients. INTERVENTIONS Study 1: OSAS patients withdrawn from treatment with CPAP. Study 2: OSAS patients treated with autoCPAP. Treatment with acetazolamide (500-750 mg) or placebo at moderate altitudes. MEASUREMENTS AND RESULTS An evening dose of 500 mg acetazolamide reduced slow-wave activity (SWA; approximately 10%) and increased spindle activity (approximately 10%) during non-REM sleep. In addition, alpha activity during wake after lights out was increased. An evening dose of 250 mg did not affect these cortical oscillations. Discontinuation of CPAP therapy revealed a reduction in SWA (5-10%) and increase in beta activity (approximately 25%). CONCLUSIONS The higher evening dose of 500 mg acetazolamide showed the "spectral fingerprint" of Benzodiazepines, while 250 mg acetazolamide had no impact on cortical oscillations. However, both doses had beneficial effects on oxygen saturation and sleep quality.

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Increased pulmonary artery pressure is a well-known phenomenon of hypoxia and is seen in patients with chronic pulmonary diseases, and also in mountaineers on high altitude expedition. Different mediators are known to regulate pulmonary artery vessel tone. However, exact mechanisms are not fully understood and a multimodal process consisting of a whole panel of mediators is supposed to cause pulmonary artery vasoconstriction. We hypothesized that increased hypoxemia is associated with an increase in vasoconstrictive mediators and decrease of vasodilatators leading to a vasoconstrictive net effect. Furthermore, we suggested oxidative stress being partly involved in changement of these parameters. Oxygen saturation (Sao2) and clinical parameters were assessed in 34 volunteers before and during a Swiss research expedition to Mount Muztagh Ata (7549 m) in Western China. Blood samples were taken at four different sites up to an altitude of 6865 m. A mass spectrometry-based targeted metabolomic platform was used to detect multiple parameters, and revealed functional impairment of enzymes that require oxidation-sensitive cofactors. Specifically, the tetrahydrobiopterin (BH4)-dependent enzyme nitric oxide synthase (NOS) showed significantly lower activities (citrulline-to-arginine ratio decreased from baseline median 0.21 to 0.14 at 6265 m), indicating lower NO availability resulting in less vasodilatative activity. Correspondingly, an increase in systemic oxidative stress was found with a significant increase of the percentage of methionine sulfoxide from a median 6% under normoxic condition to a median level of 30% (p<0.001) in camp 1 at 5533 m. Furthermore, significant increase in vasoconstrictive mediators (e.g., tryptophan, serotonin, and peroxidation-sensitive lipids) were found. During ascent up to 6865 m, significant altitude-dependent changes in multiple vessel-tone modifying mediators with excess in vasoconstrictive metabolites could be demonstrated. These changes, as well as highly significant increase in systemic oxidative stress, may be predictive for increase in acute mountain sickness score and changes in Sao2.

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Mobile ad-hoc networks (MANETs) and wireless sensor networks (WSNs) have been attracting increasing attention for decades due to their broad civilian and military applications. Basically, a MANET or WSN is a network of nodes connected by wireless communication links. Due to the limited transmission range of the radio, many pairs of nodes in MANETs or WSNs may not be able to communicate directly, hence they need other intermediate nodes to forward packets for them. Routing in such types of networks is an important issue and it poses great challenges due to the dynamic nature of MANETs or WSNs. On the one hand, the open-air nature of wireless environments brings many difficulties when an efficient routing solution is required. The wireless channel is unreliable due to fading and interferences, which makes it impossible to maintain a quality path from a source node to a destination node. Additionally, node mobility aggravates network dynamics, which causes frequent topology changes and brings significant overheads for maintaining and recalculating paths. Furthermore, mobile devices and sensors are usually constrained by battery capacity, computing and communication resources, which impose limitations on the functionalities of routing protocols. On the other hand, the wireless medium possesses inherent unique characteristics, which can be exploited to enhance transmission reliability and routing performance. Opportunistic routing (OR) is one promising technique that takes advantage of the spatial diversity and broadcast nature of the wireless medium to improve packet forwarding reliability in multihop wireless communication. OR combats the unreliable wireless links by involving multiple neighboring nodes (forwarding candidates) to choose packet forwarders. In opportunistic routing, a source node does not require an end-to-end path to transmit packets. The packet forwarding decision is made hop-by-hop in a fully distributed fashion. Motivated by the deficiencies of existing opportunistic routing protocols in dynamic environments such as mobile ad-hoc networks or wireless sensor networks, this thesis proposes a novel context-aware adaptive opportunistic routing scheme. Our proposal selects packet forwarders by simultaneously exploiting multiple types of cross-layer context information of nodes and environments. Our approach significantly outperforms other routing protocols that rely solely on a single metric. The adaptivity feature of our proposal enables network nodes to adjust their behaviors at run-time according to network conditions. To accommodate the strict energy constraints in WSNs, this thesis integrates adaptive duty-cycling mechanism to opportunistic routing for wireless sensor nodes. Our approach dynamically adjusts the sleeping intervals of sensor nodes according to the monitored traffic load and the estimated energy consumption rate. Through the integration of duty cycling of sensor nodes and opportunistic routing, our protocol is able to provide a satisfactory balance between good routing performance and energy efficiency for WSNs.

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User comfort during simulated driving is of key importance, since reduced comfort can confound the experiment and increase dropout rates. A common comfort-affecting factor is simulator-related transient adverse health effect (SHE). In this study, we propose and evaluate methods to adapt a virtual driving scene to reduce SHEs. In contrast to the manufacturer-provided high-sensory conflict scene (high-SCS), we developed a low-sensory conflict scene (low-SCS). Twenty young, healthy participants drove in both the high-SCS and the low-SCS scene for 10 min on two different days (same time of day, randomized order). Before and after driving, participants rated SHEs by completing the Simulator Sickness Questionnaire (SSQ). During driving, several physiological parameters were recorded. After driving in the high-SCS, the SSQ score increased in average by 129.4 (122.9 %, p = 0.002) compared to an increase of 5.0 (3.4 %, p = 0.878) after driving in the low-SCS. In the low-SCS, skin conductance decreased by 13.8 % (p < 0.01) and saccade amplitudes increased by 16.1 % (p < 0.01). Results show that the investigated methods reduce SHEs in a younger population, and the low-SCS is well accepted by the users. We expect that these measures will improve user comfort.

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Bluetongue virus (BTV) is an economically important member of the genus Orbivirus and closely related to African horse sickness virus (AHSV) and Epizootic hemorrhagic disease virus (EHDV). Currently, 26 different serotypes of BTV are known. The virus is transmitted by blood-feeding Culicoides midges and causes disease (bluetongue [BT]) in ruminants. In 2006/2007, BTV serotype 8 (BTV-8) caused widespread outbreaks of BT amongst livestock in Europe, which were eventually controlled employing a conventionally inactivated BTV vaccine. However, this vaccine did not allow the discrimination of infected from vaccinated animals (DIVA) by the commonly used VP7 cELISA. RNA replicon vectors based on propagation-incompetent recombinant vesicular stomatitis virus (VSV) represent a novel vaccine platform that combines the efficacy of live attenuated vaccines with the safety of inactivated vaccines. Our goal was to generate an RNA replicon vaccine for BTV-8, which is safe, efficacious, adaptable to emerging orbivirus infections , and compliant with the DIVA principle. The VP2, VP5, VP3 and VP7 genes encoding the BTV-8 capsid proteins, as well as the non-structural proteins NS1 and NS3 were inserted into a VSV vector genome lacking the essential VSV glycoprotein (G) gene. Infectious virus replicon particles (VRP) were produced on a transgenic helper cell line providing the VSV G protein in trans. Expression of antigens in vitro was analysed by immunofluorescence using monoclonal and polyclonal antibodies. In a pilot study, sheep were immunized with two different VRP-based vaccine candidates, one comprising the BTV-8 antigens VP2, VP5, VP3, VP7, NS1, and NS3, the other one containing antigens VP3, VP7, NS1, and NS3. Control animals received VRPs containing an irrelevant antigen. Virus neutralizing antibodies and protection after BTV-8 challenge were evaluated and compared to animals immunized with the conventionally inactivated vaccine. Full protection was induced only when the two antigens VP2 and VP5 were included in the vaccine. To further evaluate if VP2 alone, a combination of VP2 and VP5 or VP5 alone were necessary for complete protection, we performed a second animal trial. Interestingly, VP2 as well as the combination of VP2 and VP5 but not VP5 alone conferred full protection in terms of neutralizing antibodies, and protection from clinical signs and viremia after BTV-8 challenge. These results show that the VSV replicon system represents a safe, efficacious and DIVA-compliant vaccine against BTV as well as a possible platform for protection against other Orbiviruses, such as AHSV and EHDV.

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Adolescent development includes changes in the biological regulatory processes for the timing of sleep. Circadian rhythm changes and changes to the sleep-pressure system (sleep homeostasis) during adolescence both favor later timing of sleep. These changes, combined with prevailing social pressures, are responsible for most teens sleeping too late and too little; those who sleep least report consuming more caffeine. Although direct research findings are scarce, the likelihood of use and abuse of caffeine-laden products grows across the adolescent years due, in part, to excessive sleepiness

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REV3, the catalytic subunit of translesion polymerase zeta (polζ), is commonly associated with DNA damage bypass and repair. Despite sharing accessory subunits with replicative polymerase δ, very little is known about the role of polζ in DNA replication. We previously demonstrated that inhibition of REV3 expression induces persistent DNA damage and growth arrest in cancer cells. To reveal determinants of this sensitivity and obtain insights into the cellular function of REV3, we performed whole human genome RNAi library screens aimed at identification of synthetic lethal interactions with REV3 in A549 lung cancer cells. The top confirmed hit was RRM1, the large subunit of ribonucleotide reductase (RNR), a critical enzyme of de novo nucleotide synthesis. Treatment with the RNR-inhibitor hydroxyurea (HU) synergistically increased the fraction of REV3-deficient cells containing single stranded DNA (ssDNA) as indicated by an increase in replication protein A (RPA). However, this increase was not accompanied by accumulation of the DNA damage marker γH2AX suggesting a role of REV3 in counteracting HU-induced replication stress (RS). Consistent with a role of REV3 in DNA replication, increased RPA staining was confined to HU-treated S-phase cells. Additionally, we found genes related to RS to be significantly enriched among the top hits of the synthetic sickness/lethality (SSL) screen further corroborating the importance of REV3 for DNA replication under conditions of RS.

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Results from the Zurich study have shown lasting associations between sport practice and mental health. The effects are pronounced in people with pre-exising mental health problems. This analysis aims to replicate these results with the large Swiss Household Panel data set and to provide more differentiated results. The analysis covered the interviews 1999-2003 and included 3891 stayers, i.e., participants who were interviewed in all years. The outcome variables are depression / blues / anxiety, weakness / weariness, sleeping problems, energy / optimism. Confounding variables include sex, age, education level, citizenship. The analyses were carried out with mixed models (depression, optimism) and GEE models (weakness, sleep). About 60% of the SHP participants practise weekly or daily an individual or a team sport. A similar proportion enjoys a frequent physical activity (for half an hour minimum) which makes oneself slightly breathless. There are slight age-specific differences but also noteworthy regional differences. Practice of sport is clearly interrelated with self-reported depressive symptoms, optimism and weakness. This applies even though some relevant confounders – sex, educational level and citizenship – were introduced into the model. However, no relevant interaction effects with time could be shown. Moreover, direct interrelations commonly led to better fits than models with lagged variables, thus indicating that delayed effects of sport practice on the self-reported psychological complaints are less important. Model variants resulted for specific subgroups, for example, participants with a high vs. low initial activity level. Lack of sport practice is an interesting marker for serious psychological symptoms and mental disorders. The background of this association may differ in different subgroups, and should stimulate further investigations in this area.

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Species belonging to the Culicoides complexes (Diptera, Ceratopogonidae), obsoletus and pulicaris, in Switzerland, are potential vectors of both bluetongue virus (BTV) and African horse sickness virus (AHSV). The epidemic of BTV in 2006 and 2007 in Europe has highlighted the risk of introduction and spread of vector-borne diseases in previously non-endemic areas. As a measure of prevention, as part of an integrated control programme in the event of an outbreak of African horse sickness (AHS), it is of utmost importance to prevent, or substantially reduce, contact between horses and Culicoides. The aim of the present study was to compare the effect of three protection systems, net, fan, repellent, or combinations thereof, with regard to their potential to reduce contact between horses and Culicoides. Three different equine housing systems, including individual boxes (BX), group housing systems (GR), and individual boxes with permanently accessible paddock (BP) were used. The efficacy of the protection systems were evaluated by comparing the total number counts of collected female Culicoides, of non-blood-fed and blood-fed Culicoides, respectively, with UV black light traps. The study was conducted over 3 summer months during 2012 and 2013 each and focused on the efficacy and practicality of the protection systems. The repellent was tested in 2012 only and not further investigated in 2013, as it showed no significant effect in reducing Culicoides collected in the light traps. Net protection system provided the best overall protection for the total number of female Culicoides, non-blood-fed and blood-fed Culicoides in all tested housing systems. The net, with a pore size of 0.1825 mm(2), reduced the total number of Culicoides collected in the housing systems BP, GR and BX by 98%, 85% and 67%, respectively. However, in the GR housing system, no significant difference between the effectiveness of the fan and the net were determined for any of the three Culicoides categories. The results of the present study demonstrated that horse owners can substantially reduce their horses' exposure to Culicoides, by using net protection in the housing systems BX, BP and GR. In GR housing systems, protection against Culicoides using a fan is also recommended.