Hot spot identification method based on Andrews curves: an application on the COVID-19 crisis effects on caregiver distress in neurocognitive disorder.

Identifying and locating areas - hot spots - that present high concentration of observations in a high-dimensional data set is crucial in many data processing and analysis methods and techniques, since observations that belong to the same hot spot share information and behave in a similar way. A useful tool towards that aim is the reduction of the data dimensionality and the graphical representation of them. In the present paper, a new method to identify and locate hot spots is proposed, based on the Andrews curves. Simulations results demonstrate the performance of the proposed method, which is also applied to a high-dimensional data set, regarding caregiver distress related to symptoms of people with neurocognitive disorder and to the mental effects of the recent outbreak of the COVID-19 pandemic.

Old age mental health services in Southern Balkans: Features, geospatial distribution, current needs, and future perspectives.

BACKGROUND: Healthcare services are increasingly confronted with challenges related to old age mental disorders. The survey aimed to provide an overview of existing psychogeriatric services in Albania, Bulgaria, Greece, and North Macedonia. METHODS: After identification of psychogeriatric units across the four countries, their head physicians were asked to provide data on their clinical, teaching, and research activity, as well as staff composition. Moreover, the attitudes of head physicians to current needs and future service development were explored. RESULTS: A total of 15 psychogeriatric units were identified (3 in Bulgaria, 8 in Greece, and 4 in North Macedonia). Results show wide variation regarding the location, team size and composition, service availability, numbers of patients attending, and inpatient treatment length. Most head physicians underscored the urgent need for breakthroughs in the graduate and postgraduate education in psychogeriatrics of medical and nonmedical professionals, as well as in the interconnection of their units with community primary healthcare services and long-term care facilities for seniors via telemedicine. They would welcome the development of national standards for psychogeriatric units, potentially embodying clear pointers for action. A number of head physicians advocated the development of nationwide old age mental health registries. CONCLUSIONS: Regional disparities in resources and services for seniors' mental health services were unveiled. These data may enrich the dialogue on optimizing psychogeriatric services through planning future cross-border collaborations mainly based on telemedicine services, especially in the era of the novel coronavirus pandemic, and training/education in psychogeriatrics of mental health professionals.

[European Join Action on Dementia: Dementia Friendly Communities in Greece (DFC), the project "Aeneas"].

The Health Care system has a vital role in improving services and support people with dementia, but it cannot prevent fear and lack of understanding of dementia. Lack of awareness and poor understanding in communities has a major impact on the experience of people with dementia and their caregivers. "Dementia Friendly Communities" is a program of EU as part of the Act on Dementia Joint Action, in order to advance common recommendations for the development of better services for people with dementia, which will improve their quality of life. Ιt has been proposed that within a "Dementia friendly Community, people with dementia will not be marginalized and will be respected by their fellow citizens. The citizens, the public organizations and private sector enterprises cooperate in order to eliminate the obstacles which exclude dementia patients and their caregivers from participating in the life of their community". The Dementia Friendly Communities involve four fields: the environment (places), the citizens (people), the networks and the resources. Based on this model, pilot actions have been developed in Greece (Municipalities of Athens, Byron and Vrilissia), Bulgaria and UK and it is expected to provide important guidelines for the development of Dementia Friendly Communities in EU. In Greece the goal of the Join Action on Dementia was to promote the development of strong alliances within the local communities (municipalities) and the networking of organizations (State, Municipalities, NGOs, enterprises etc) with dementia patients and their caregivers and to educate more people in the municipalities in order to fight stigma and understand dementia.

[The effect of physical activity on dementia].

Τhe rate of patients suffering from mild cognitive impairment or any type of dementia has been constantly on the rise. Considering that no effective treatment of dementia has been discovered to date and that drug use can have numerous side effects, there is an urgent need for the application of alternative, non-pharmacological interventions. To this end, the aim of this study was to investigate the effects of physical activity on the cognitive impairment of the elderly, and its use as a form of non-pharmacological intervention for the treatment of dementia. Taking a review of the relevant literature, as its data collection method, this study examined peer-reviewed papers published between 2010 and 2018 that met the criteria for their inclusion. The articles were drawn from three electronic databases (PubMed, ScienceDirect and Web of Science), and were examined with regard to the populations under consideration, research design, type of intervention programs and assessment tools applied. The vast majority of these research papers tend to support that physical activity offers significant benefits to people suffering from Alzheimer's disease or other dementias. Specifically, it helps stabilize and improve cognitive function as well as reduce and delay the onset of severe neuropsychiatric symptoms such as depression, confusion, apathy, etc. In addition, physical exercise plays an important role in improving the executive functioning of patients with dementia, increasing autonomy in their everyday activities and reducing the risk of falls. In conclusion, recent research shows physical activity to be a promising intervention for the prevention and non-pharmacological treatment of dementia in that it contributes to the improvement of patients' quality of life. However, results vary according to the particularly characteristics of the exercise under review, such as type, intensity, frequency, and duration. It is therefore important to gain both awareness and understanding of the specific factors that give physical activity its therapeutic potential leading to the development of exercise programs designed specially to treat dementia.

Extensive countrywide field investigation of subclinical mastitis in sheep in Greece.

The objectives of this work were (1) to investigate prevalence of subclinical mastitis, (2) to identify etiological agents involved, and (3) to study factors potentially predisposing ewes to subclinical mastitis. Milk samples were collected from 2,198 ewes in 111 farms with a total population of 35,925 ewes, in all 13 administrative regions of Greece, for bacteriological and cytological examination. Prevalence of subclinical mastitis was 0.260. Main etiological agents were staphylococci (Staphylococcus aureus and coagulase-negative species), which accounted for 0.699 of all isolates recovered; prevalence of staphylococcal mastitis was 0.191. In a multivariable mixed-effects analysis, the primary factor found to be associated with increased prevalence of subclinical mastitis was the management system practiced in flocks (flocks under a semi-intensive system had the highest prevalence). Other factors that were included in the multivariable model were the stage of lactation period (ewes in the 2nd month postpartum showed the highest prevalence) and application of postmilking teat dipping. In contrast, measures taken at the end of a lactation period (e.g., intramammary administration of antimicrobial agents) were not found to have an effect on prevalence of subclinical mastitis. The results confirmed the significance of subclinical mastitis as a frequent problem of ewes, with staphylococci as the primary etiological agent. The findings confirm the multifactorial nature of subclinical mastitis and indicate that its control should rely on many approaches.

Assessing depression in Greek dementia patients: Which scale to use?

Depression in dementia is known to deteriorate patients' cognitive function and Quality of Life and to increase the burden of care. Although detecting depression in dementia is crucial, there is no gold standard for its screening and diagnosis. We examined the psychometric properties of 3 different scales in detecting depression in dementia. Results will be useful as community services for dementia in the country are developing and the need for reliable detection of depression in dementia patients is urgent. Our sample consisted of 136 Greek dementia patients who consulted a memory clinic. For the diagnosis of depression, DSM-IV criteria for major depression and 3 different depression measures were used: a self-assessment scale (Geriatric Depression Scale; GDS), a caregiver assessment scale (Neuropsychiatric Inventory-Depression; NPI-D) and a clinician rated scale (Cornell Scale for Depression in Dementia; CSDD). For the evaluation of the screening performance of the three depression scales receiver operating characteristic curve (ROC) analysis was applied. The DSMIV criteria served as the gold standard method for the diagnosis of major depression. CSDD showed the best psychometric properties for the diagnosis of depression in dementia. The ROC curve analysis revealed that among the three measures, the CSDD had the wider AUC (0.919), second in the width of the AUC was the GDS (0.871), and last was the NPI-D (0.812). The prevalence of depression ranged from 18.4% according to DSM-IV criteria to 42.6% using the NPI-D. Using the GDS (cut off point: 7/8) and the CSDD (cut off point: 6/7), depression was present in 26.9% and 33.1% of the patients, respectively. Correlations between scales used were significant (r from 0.432 to 0.660; p<0.001). Caregivers tend to report more depressive symptoms in dementia compared to patients' and clinicians' ratings. CSDD should be used in specialized centers, but GDS may be an alternative in patients able to complete the assessment. The need to establish valid criteria for the diagnosis of depression in dementia is urgent.

[Pro-inflammatory cytokines in Alzheimer's disease].

Alzheimer's disease (AD), the most common progressive neurodegenerative disorder in the elderly, is clinically characterized by progressive impairment of cognitive functions, including reduced critical capacity, weakness of decision-making and problem orientation, while in the more advanced stages it is accompanied by behavioral disorders and impaired verbal ability. Neuropathological characteristics of the disease are the neurofibrillary tangles (NFT), the neuritic plaques (NP), the prominent synaptic loss and eventually the neuronal loss. The presence of inflammatory process seems to be playing important role in the progression of the disease. This process is directed by the activated glial cells and it leads to the overproduction of acute phase proteins, complement factors activation and induction of inflammatory enzyme systems. These inflammatory factors can contribute to neuronal dysfunction and cell death. Cytokines belong to the acute phase proteins, which are secreted from glial cells. They can either strengthen the inflammatory reaction or suppress it, adjusting the intensity and duration of the immune response. In the category of cytokines belong several interleukins (ILs) and various factors (TNF-α, TGF-ß). Interleukins are involved in complex intercellular interactions among neurons, microglia and astrocytes, as well as intracellular signal transduction events, which are necessary to promote the inflammatory cascade characteristic of AD neuropathology. It has been observed that increased levels of pro- inflammatory cytokines, including tumor necrosis factor (TNF), interleukin 1ß (IL-1ß), interleukin 6 (IL-6) and interferon γ (IFN-γ), may suspend phagocytosis of amyloid Aß in brains of patients with AD. Thus, it may interfere with the effective removal of plaque from microglia, promote astrogliosis and neural death. Normally, during immune surveillance, a balance is maintained between pro- and antiinflammatory influences. Yet, during AD, the abnormal accumulation of soluble amyloid oligomers triggers excessive release of pro inflammatory factors, such as cytokines and other acute-phase reactants, out of proportion to the regulatory components, such as IL-4, IL-10, receptor antagonists, interleukin inhibitors and others, ultimately leading to neuronal and synaptic injury and loss and cognitive decline. These changes in the brain parenchyma are often accompanied by changes in levels of these inflammatory proteins in peripheral blood. Even though literature is presenting conflicting studies, efforts are being made for the detection of cytokines in peripheral blood and association of their levels with the progression of AD. Inflammatory pathways, involving the signaling of cytokines, could be potential targets for the prevention of AD and the development of new therapies. The aim of the present work is to review studies indicating a correlation between these inflammatory agents and AD pathogenesis.

The burden of caring for patients with dementia and its predictors.

Dementia not only affects patients but also care providers. The assessment of Caregivers' Burden (CB) has grown exponentially in the dementia field, as studies have shown that it is higher in dementia than in other diseases. Dementia care in Greece is different compared to other developed countries, as most of the patients receive care at home from family members. The aim of the present study was to examine the level of burden in Greek caregivers who live in Athens, and its association with patient and caregiver factors. This was a cross-sectional study of 161 primary caregivers of dementia patients living in the community and attending a secondary clinic. CB was assessed with the Zarit Burden Interview (ZBI) and caregivers' depression with the Center for Epidemiological Studies Depression Scale (CES-D). Clinical characteristics of the patients were also assessed using validated scales (cognitive status, functional ability, neuropsychiatric symptoms). In order to find predictors of caregiver Burden, we conducted a 3-step hierarchical regression analysis. Most patients were suffering from Alzheimer's Dementia (n=101; 62.73%) and had moderate and severe dementia according to the MMSE score (mean MMSE=11.50), with patients being unable to perform 2 basic activities of daily living on average. 45 patients (27.95%) had depression according to the CSDD; only 5 patients didn't have any behavioral problem in the NPI, while patients had more than 5 behavioral problems on average. Caregivers were involved in their role for 3.6 years on average and the mean weekly caregiving time was more than 70 hours. Nearly half (n=80; 49.06%) of the 161 caregivers demonstrated high CB (ZBI>40) and nearly one fourth had depression according to the CES-D scale. All blocks of variables entered into the regression model independently predicted caregiver burden's variance (demographics, clinical factors and caregiving characteristics). Lower caregiver's age, high behavioral symptoms of dementia patients and caregivers' depression were found to be independently associated with CB. The final regression model explained 47.2% of the variance in CB. Dementia causes a great burden in caregivers. CB is a complex issue that is associated with several patients and caregivers' factors. The level of CB should be assessed in everyday dementia clinical practice.

[Mini Mental State Examination (MMSE): determination of cutoff scores according to age and educational level].

For the last 38 years, Mini Mental State Examination (MMSE) has been widely used as a dementia screening measure in everyday clinical practice as well as in both cohort and cross-sectional studies. Its validity and reliability for the Greek population has explicitly been documented. However, the effect of age and education on the subject's performance makes it necessary to reckon them in the estimation of the "cutoff score". The purpose of this study is to estimate the prevalence of dementia in Greek population and determine the "cutoff score" by age and education-corrected norms. Cross sectional study of 630 patients older than 55 years, who live independently in Ilion and Helioupolis Municipalities was conducted, 27.3% of the subjects tested in the study were diagnosed with memory disorder according to their MMSE scores and the validation for the Greek population. The effect of age and education to the subjects' performance was statistically significant (p=.000). The use of standard "cutoff score" was not proved to be useful for the personalized interpretation of the results, as documented by the fact that older individuals with lower education had a poorer performance relatively to younger, highly educated subjects. Comparatively to the group age of 55-60 years, the odds ratio after the age of 75 years varies from 2.58 to 4.91. Regarding the variable factor of education, the odds ratio for the first degree education graduates decreases from 1.43 to 3.19 for the third degree education graduates in comparison with the group of illiterates. In conclusion, the use of the "cutoff score" algorithm and the simultaneous estimation of age and education effect on MMSE score may prove useful for the proper evaluation of MMSE performance. According to the age and education of examine candidates in the community and the primary care, we propose the use of the 25th percentile as a more useful cutoff score in order to decrease the false positive results.

Loading rate patterns in scoliotic children during gait: the impact of the schoolbag carriage and the importance of its position.

PURPOSE: Concerns have been raised regarding the effects of schoolbag carriage on adolescent schoolchildren and particularly those with a pre-existing spinal deformity. The purpose of this study was to determine the effect of school backpack loads in scoliotic and healthy school-age children during walking, in terms of peak vertical ground reaction forces and loading rates. We hypothesized that walking with a loaded backpack would have a greater effect on gait kinetics of scoliotic compared to healthy. METHODS: Eight children with idiopathic scoliosis and eight healthy children were assessed. Kinetic data were collected using two AMTI OR6-7 force-plates, while the subjects walked freely along a 6-m walkway under three walking conditions: (1) without a schoolbag, (2) carrying a schoolbag bilaterally (over both shoulders-symmetrical load) and (3) carrying a schoolbag unilaterally (over each shoulder-asymmetrical load). Kinetic data were collected and four parameters were calculated; peak ground reaction force at the first maximum force peak (F1), time needed to reach F1 (T1), loading rate of F1 (LRF1) and total contact time (T2). RESULTS: We found no significant differences between the scoliotic and healthy children for any of the kinetic variables examined. In addition, the position of the bag did not seem to have any effect on loading rate. CONCLUSIONS: The results of this study indicate that in terms of kinetic parameters during normal gait, the schoolbag load (symmetrical or asymmetrical) does not have a different effect on children with mild adolescent idiopathic scoliosis compared to normal controls.

The Neuropsychiatric Inventory-Clinician rating scale (NPI-C): reliability and validity of a revised assessment of neuropsychiatric symptoms in dementia.

BACKGROUND: Neuropsychiatric symptoms (NPS) affect almost all patients with dementia and are a major focus of study and treatment. Accurate assessment of NPS through valid, sensitive and reliable measures is crucial. Although current NPS measures have many strengths, they also have some limitations (e.g. acquisition of data is limited to informants or caregivers as respondents, limited depth of items specific to moderate dementia). Therefore, we developed a revised version of the NPI, known as the NPI-C. The NPI-C includes expanded domains and items, and a clinician-rating methodology. This study evaluated the reliability and convergent validity of the NPI-C at ten international sites (seven languages). METHODS: Face validity for 78 new items was obtained through a Delphi panel. A total of 128 dyads (caregivers/patients) from three severity categories of dementia (mild = 58, moderate = 49, severe = 21) were interviewed separately by two trained raters using two rating methods: the original NPI interview and a clinician-rated method. Rater 1 also administered four additional, established measures: the Apathy Evaluation Scale, the Brief Psychiatric Rating Scale, the Cohen-Mansfield Agitation Index, and the Cornell Scale for Depression in Dementia. Intraclass correlations were used to determine inter-rater reliability. Pearson correlations between the four relevant NPI-C domains and their corresponding outside measures were used for convergent validity. RESULTS: Inter-rater reliability was strong for most items. Convergent validity was moderate (apathy and agitation) to strong (hallucinations and delusions; agitation and aberrant vocalization; and depression) for clinician ratings in NPI-C domains. CONCLUSION: Overall, the NPI-C shows promise as a versatile tool which can accurately measure NPS and which uses a uniform scale system to facilitate data comparisons across studies.

Heterotopic ossification after total hip arthroplasty (THA) in congenital hip disease: comparison of two different prophylactic protocols.

INTRODUCTION: We aimed to evaluate retrospectively the efficacy of combined postoperative radiotherapy and indomethacin compared to indomethacin alone for the prevention of heterotopic ossification (HO) in high-risk patients with congenital disease of hip (CDH) undergoing total hip arthroplasty (THA). MATERIALS AND METHODS: Fifty-five patients received indomethacin alone (Group A), while 44 patients received the combined protocol (Group B). Patients >or=55 years were enrolled in Group B and those younger than 55 years in Group A. Patients were evaluated radiologically for the presence of HO 6 months after the operation. RESULTS: The incidence of HO in Group A was 34.5% (95% confidence interval 22.2-48.6%), while the respective incidence in Group B patients was 27.3% (95% CI 15.0- 42.8%). The difference was not statistically significant (p=0.5). No significant treatment-related side effects were reported. CONCLUSIONS: This is the first study evaluating the impact of HO prophylaxis in an immiscible population of patients with secondary arthritis due to CDH undergoing THA. Further future randomised evidence is required in order to ascertain the observed trend towards improved efficacy of the combined protocol for HO development.

Effect of interlaminar epidural steroid injection in acute and subacute pain due to lumbar disk herniation: a randomized comparison of 2 different protocols.

In order to assess the efficacy of epidural steroid injections (ESI) in acute and subacute pain due to lumbar spine disk herniation, we conducted a randomized trial, comparing 2 different protocols. Fourty patients with radicular pain due to L4-L5 and L5-S1 disc herniation were assigned to receive either 3 consecutive ESI every 24 hours through a spinal catheter (group A) or 3 consecutive ESI every 10 days with an epidural needle (group B). All patients had improved Oswestry Disabilty Index (ODI) and the Visual Analog Scale (VAS) for pain scores at 1 month of follow-up compared to baseline, while no significant differences were observed between the 2 groups. The scores for group B were statistically significant lower at 2 months of follow-up compared to those of group A. The improvement in the scores of group B was continuous since the mean scores at 2 months of follow up were lower compared to the respective scores at 1 month. Protocol B (3 consecutive ESI every 10 days) was found more effective in the treatment of subacute pain compared to Protocol A (3 consecutive ESI every 24 hours) with statistically significant differences in the ODI and VAS scores at 2 months of follow-up.

Acquired competence in cognitive therapy following a two level course.

The objective of this study was to examine the predictive value of trainees' previous experience and performance at an introductory course in Cognitive Therapy for their subsequent success in an advanced course. From 203 completers of an introductory course during seven consecutive years 32 participated in an advanced course. In a linear regression analysis previous clinical and psychotherapeutic experience as well as performance at the introductory course were studied as predictors for trainees' success in the advanced course. Performance at the introductory course was the only significant predictor of trainees' successful completion of the advanced course. An introductory course might help to select those trainees who have the desired qualities to succeed in a formal psychotherapeutic training program.

Numerical modelling of simulated blood flow in idealized composite arterial coronary grafts: transient flow.

In composite arterial coronary grafts (CACGs), transport phenomena and geometry may considerably alter blood flow dynamics. CACGs aim at revascularizing pathological arteries according to the human anatomy. However, the exact mechanisms causing the failure of coronary bypass grafting are not yet well elucidated. In the present study, computational fluid dynamics (CFD) techniques are applied for the simulation of multi-branched CACGs under physiologically realistic inflow waveforms. The numerical solution is obtained by a finite-volume method formulated in non-orthogonal, curvilinear coordinates and a multi-grid approach. The geometrical models, consisting of idealized and rigid vessels, include the typical T- and a rather new pi-graft configuration. The stenotic effect is also investigated by comparing computational results for three different degrees of area constriction, namely 25%, 50% and 75%, as well as the case without stenosis. Different grafting distances and various inflow rate ratios are imposed, to give an insight into haemodynamical alterations of CACGs and to study the process of restenosis. The results focus on the interaction between the grafts and coronary flows in terms of spatial and temporal variations of velocity and wall shear stress (WSS) distribution. Prominent variations among the different geometries, concerning the velocity profiles and secondary flow motion, are shown. Moreover, the residual flow emerging from different degrees of area constriction shows that low and oscillating shear stresses may arise for even moderate stenotic fields.

Numerical modeling of simulated blood flow in idealized composite arterial coronary grafts: steady state simulations.

This paper presents a comparative study of simulated blood flow in different configurations of simplified composite arterial coronary grafts (CACGs). Even though the composite arterial grafting is increasingly used in cardiac surgery, it is still questionable whether or not the blood flow in such grafts can adequately meet the demands of the native myocardial circulation. A computational fluid dynamics (CFD) model was developed to conduct computer-based studies of simulated blood flow in four different geometric configurations of CACGs, corresponding to routinely used networks in cardiac surgery coronary grafts (T, Y, Pi and sequential). The flow was assumed three-dimensional, laminar and steady and the fluid as Newtonian, while the vessel walls were considered as inelastic and impermeable. It was concluded that local haemodynamics, practically described by velocity, pressure drop, wall shear stress (WSS) and flow rates, may be strongly influenced by the local geometry, especially at the anastomotic sites. The computations were made at mean flow rates of 37.5, 75 and 150ml/min. The side-branch outflow rates, computed for each bypass graft, showed noticeable differences. The results, which were found both qualitatively and quantitatively consistent with other studies, indicate that the Pi-graft exhibits significantly less uniform distribution of outflow rates than the other geometric configurations. Moreover, prominent variations in WSS and velocity distribution among the assessed CACGs were predicted, showing remarkable flow interactions among the arterial branches. The lowest shear stress regions were found on the lateral walls of bifurcations, which are predominantly susceptible to the occurrence of coronary artery disease (CAD). In contrast, the highest WSS were observed at the turn of the arterial branches.

Development and use of online mental health services in Greece.

E-mental health refers to the use of telecommunication and information technology in mental health services. In Greece, ordinary telephone communications have been used to provide mental health services, such as a psychiatric crisis intervention line (METB). E-psychiatry is a relatively new approach to delivering psychiatric services through the Internet. We have developed an e-psychiatry Website, Glaucopis-net. The main objective is to provide information on a broad range of psychiatric conditions, such as dementia, depression and anxiety. Email mental health services will be offered as an alternative way of accessing help. Confidentiality issues concerning patient records and personal data will be treated in accordance with Greek legislation. Glaucopis-net will integrate new telecommunication and information services with classical mental health services.

Regulation of IFN consensus sequence binding protein expression in murine macrophages.

Recent work has demonstrated that the transcription factor, IFN consensus sequence binding protein (ICSBP), plays a critical role in the capacity of mice to control infection with Toxoplasma gondii and Leishmania major, agents that require highly activated macrophages for their elimination. In this report the regulation of ICSBP mRNA and protein were analyzed in murine macrophages stimulated with LPS and/or IFN-gamma. Like induction of leishmaniacidal activity, LPS and IFN-gamma synergize to induce ICSBP mRNA and protein. Deletion analysis of the ICSBP promoter identified regions that were IFN-gamma responsive, regions that mediate the ability of LPS and IFN-gamma to activate this promoter synergistically, as well as regions that normally repress ICSBP transcription. Finally, exogenous expression of ICSBP, found in previous studies to down-regulate MHC I gene expression, failed to repress basal or IFN-gamma-induced ICSBP transcription. This demonstrates that ICSBP can selectively suppress the expression of IFN-responsive genes. These findings extend in a significant way our understanding of the regulation of ICSBP by LPS and IFN-gamma and provide important clues as to its role in macrophage activation.

Molecular interactions between interferon consensus sequence binding protein and members of the interferon regulatory factor family.

Interferon (IFN) consensus sequence binding protein (ICSBP) is a transcription factor expressed mostly in the cells of the immune system. ICSBP belongs to the IFN regulatory factor (IRF) family, which also includes IRF-1, IRF-2, and the IFN-alpha-stimulated gene factor 3 gamma (ISGF3 gamma). We show here that ICSBP forms a complex with IRF-1 or IRF-2 both in vivo and in vitro and, in the presence or absence of the target DNA, with the IFN-stimulated response element (ISRE). Further, electrophoretic mobility shift assays show that this interaction greatly enhances the otherwise very low binding affinity of ICSBP to the ISRE. We show, on the other hand, that ICSBP inhibits binding of the IFN-alpha-stimulated gene factor 3 gamma to the ISRE. Through these interactions ICSBP is likely to exert complex modulatory functions in the regulation of IFN-stimulated genes.