Human Cytomegalovirus Oncoprotection across Diverse Populations, Tumor Histologies, and Age Groups: The Relevance for Prospective Vaccinal Therapy.

The oncogenicity of the human cytomegalovirus (CMV) is currently being widely debated. Most recently, mounting clinical evidence suggests an anti-cancer effect via CMV-induced T cell-mediated tumor destruction. However, the data were mostly obtained from single-center studies and in vitro experiments. Broad geographic coverage is required to offer a global perspective. Our study examined the correlation between country-specific CMV seroprevalence (across 73 countries) and the age-standardized incidence rate (of 34 invasive tumors). The populations studied were stratified according to decadal age periods as the immunologic effects of CMV seropositivity may depend upon age at initial infection. The International Agency for Research on Cancer of the World Health Organization (IARC WHO) database was used. The multivariate linear regression analysis revealed a worldwide inverse correlation between CMV seroprevalence and the incidences of 62.8% tumors. Notably, this inverse link persists for all cancers combined (Spearman's ρ = -0.732, p < 0.001; ß = -0.482, p < 0.001, adjusted R2 = 0.737). An antithetical and significant correlation was also observed in particular age groups for the vast majority of tumors. Our results corroborate the conclusions of previous studies and indicate that this oncopreventive phenomenon holds true on a global scale. It applies to a wide spectrum of cancer histologies, additionally supporting the idea of a common underlying mechanism-CMV-stimulated T cell tumor targeting. Although these results further advance the notion of CMV-based therapies, in-depth investigation of host-virus interactions is still warranted.

Significance of Cytomegalovirus gB Genotypes in Adult Patients Undergoing Hematopoietic Stem Cell Transplantation: Insights from a Single-Centre Investigation.

INTRODUCTION: Cytomegalovirus (CMV) infection is a major clinical issue after allogeneic hematopoietic stem cell transplantation (HSCT). The CMV envelope glycoproteins are key in viral pathogenesis; the glycoprotein B (gB) encoded by the UL55 gene might be an important determinant of viral virulence and disease severity marker in patients treated with allogeneic HSCT. Our aim was to investigate the molecular diversity of CMV gB and inquire into the associations between UL55 gene variations and clinical manifestations in adult patients treated with allogeneic HSCT. RESULTS: The most prevalent genotypes were gB1 and gB4 (11/27, 40.7%). Patients with genotype gB1 infection had earlier platelet engraftment (p < 0.033) and less frequent minimal/measurable residual disease post HSCT than those without this genotype. Patients with gB4 glycoprotein infection had a significantly lower CD4+/CD8+ ratio at D90 (p < 0.026). Interestingly, patients with gB5 glycoprotein infection had shorter overall survival from base condition diagnosis (p < 0.042), as well as shorter overall survival after HSCT (p < 0.036). Acute GvHD was noted more frequently in those with mixed-genotype infection (p = 0.047). MATERIAL AND METHODS: The study included fifty-nine adult patients treated with allogeneic HSCT. Peripheral venous blood was sampled typically per week, with detection of CMV performed by quantitative real-time PCR. Multiplex nested PCR was used to determine specific gB genotypes, which were then statistically compared vis-à-vis specific clinical variables. CONCLUSIONS: Our study points to variations in the viral UL55 locus imparting both beneficial (earlier platelet engraftment, less frequent MRD post HSCT) and adverse effects (shorter overall survival, more frequent acute GvHD, less frequent 100% chimerism at day 90) to the transplanted host. Comprehensive molecular investigations are necessary to validate this apparent duality, as the potential benefits of CMV could perhaps be utilized for the benefit of the patient in the future.

Friend or Foe? Exploring the Role of Cytomegalovirus (HCMV) Infection in Head and Neck Tumors.

Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings.

Genome sequence diversity of SARS-CoV-2 in Serbia: insights gained from a 3-year pandemic study.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, has been evolving rapidly causing emergence of new variants and health uncertainties. Monitoring the evolution of the virus was of the utmost importance for public health interventions and the development of national and global mitigation strategies. Here, we report national data on the emergence of new variants, their distribution, and dynamics in a 3-year study conducted from March 2020 to the end of January 2023 in the Republic of Serbia. Nasopharyngeal and oropharyngeal swabs from 2,398 COVID-19-positive patients were collected and sequenced using three different next generation technologies: Oxford Nanopore, Ion Torrent, and DNBSeq. In the subset of 2,107 SARS-CoV-2 sequences which met the quality requirements, detection of mutations, assignment to SARS-CoV-2 lineages, and phylogenetic analysis were performed. During the 3-year period, we detected three variants of concern, namely, Alpha (5.6%), Delta (7.4%), and Omicron (70.3%) and one variant of interest-Omicron recombinant "Kraken" (XBB1.5) (<1%), whereas 16.8% of the samples belonged to other SARS-CoV-2 (sub)lineages. The detected SARS-CoV-2 (sub)lineages resulted in eight COVID-19 pandemic waves in Serbia, which correspond to the pandemic waves reported in Europe and the United States. Wave dynamics in Serbia showed the most resemblance with the profile of pandemic waves in southern Europe, consistent with the southeastern European location of Serbia. The samples were assigned to sixteen SARS-CoV-2 Nextstrain clades: 20A, 20B, 20C, 20D, 20E, 20G, 20I, 21J, 21K, 21L, 22A, 22B, 22C, 22D, 22E, and 22F and six different Omicron recombinants (XZ, XAZ, XAS, XBB, XBF, and XBK). The 10 most common mutations detected in the coding and untranslated regions of the SARS-CoV-2 genomes included four mutations affecting the spike protein (S:D614G, S:T478K, S:P681H, and S:S477N) and one mutation at each of the following positions: 5'-untranslated region (5'UTR:241); N protein (N:RG203KR); NSP3 protein (NSP3:F106F); NSP4 protein (NSP4:T492I); NSP6 protein (NSP6: S106/G107/F108 - triple deletion), and NSP12b protein (NSP12b:P314L). This national-level study is the most comprehensive in terms of sequencing and genomic surveillance of SARS-CoV-2 during the pandemic in Serbia, highlighting the importance of establishing and maintaining good national practice for monitoring SARS-CoV-2 and other viruses circulating worldwide.

Variations of salinity during reproduction and development affect ontogenetic trajectories in a coastal amphibian.

Although coastal ecosystems are naturally submitted to temporal variations of salinity, salinization has been increasing over time threatening coastal biodiversity. Species that exploit such habitats can thus be exposed to brackish water at different life stages. However, the impacts of variations of salinity on wildlife remain poorly understood. This is particularly true for coastal amphibians, due to the strong dependency of early life stages (embryos and larvae) on aquatic environments. In order to investigate the effect of salinity during egg laying and embryonic and larval development of coastal amphibians, we used a full-factorial design to expose reproductive adults, eggs, and larvae of coastal spined toads (Bufo spinosus) to fresh (0 g.l-1) or brackish water (4 g.l-1). At egg laying, we evaluated parental investment in reproduction. During embryonic and larval development, we assessed effects on survival, development, and growth. We highlighted strong effects of environmental salinity on reproduction (reduced egg laying time, marginally reduced egg size, and reduced investment in reproduction). Responses to salinity were highly dependent on the developmental stages of exposure (stronger effects when individuals were exposed during embryonic development). These effects carried over when exposure occurred at egg laying or during embryonic development, highlighting the importance of the environmental conditions during early life on ontogenetic trajectories. We also highlighted partial compensation when individuals were transferred back to freshwater. Whether the magnitude of these responses can allow coastal biodiversity to overcome the observed detrimental effects of salinization remain to be assessed.

Understanding the Dynamics of Human Papillomavirus and Diagnostic Discrepancies in Cervical Pathology: A Single Center Experience.

Cervical cancer (CC) is the most prevalent gynecological malignancy and a leading cause of death among women. It is primarily caused by human papillomavirus (HPV) infection, with 99.7% of cases showing high-risk HPV genotypes. This study sheds light on HPV dynamics as well as the discrepancies of different CC screening modalities results while highlighting factors that may have contributed to such a scenario. Moreover, we underscore the importance of the non-viral etiology of CC as well. We examined the current trends of HPV infection and its effects on cervical health in women treated at a tertiary care center in Belgrade, Serbia. Patients with abnormal colposcopy findings like dysplasia and re-epithelization were more likely to test negative for HPV (p < 0.001). Interestingly, women with a positive Pap smear tested HPV negative significantly more often (p = 0.041). Finally, HPV-positive individuals were more likely to have CIN I and II histologies (p < 0.001), while CIN III occurred equally in women with and without the virus. It may be inferred that inconsistencies in detecting HPV and the presence of cervical lesions may eventually result in adjustments to screening guidelines, as is crucial to adopt a meticulous approach to promote periodical CC screening, as initial samples may test negative for HPV.

Long-term trends of salinity in coastal wetlands: Effects of climate, extreme weather events, and sea water level.

Coastal freshwater ecosystems play major roles as reservoirs of biodiversity and provide many ecosystem services and protection from extreme weather events. While they are of particular importance worldwide, they are affected by a large variety of anthropogenic threats, among which salinization has been less studied, particularly regarding large temporal and spatial data sets based on real case scenarios, while salinity can impact biodiversity and ecosystem functioning. In this study, we investigated the variations of salinity across long-term (1996-2020) and seasonal (monthly records) temporal scales and spatial (varying distance to the coastline) scales in water bodies of two typical temperate coastal wetlands situated on the Atlantic coast of France. We complemented our analyses with models of sea water levels computed at both sites across 2000-2020. Our detailed data set allowed for highlighting that salinity in ponds varied seasonally (higher during summer, due to decreased precipitation and higher temperature), but also spatially (higher closer to the seashore, which pattern increased through time). Over the long term, decreased precipitation but not increased temperature induced increasing salinity. We also highlighted contrasted long-term patterns of salinity changes on these two coastal wetlands, with one site were salinity decreased over time linked to the responses to marine flood, allowing to document the temporal dynamics of salinity following a massive intrusion of sea water. Complementarily, at both sites, water levels at high tides increased through time, a pattern which can induce additional salinization. To our knowledge, our study is the first to investigate long-term changes in salinity in coastal wetlands through natural processes (e.g. seaspray, seasonal variations) and ongoing climate perturbations (e.g. marine surges linked to extreme weather events, increased temperature and decreased precipitations).

Detection of the Xanthi Chryso-like Virus in New Geographical Area and a Novel Arthropod Carrier.

Here, we report on a serendipitous finding of a chryso-like virus associated with Culex pipiens mosquitos in the course of study aimed to detect and characterize West Nile virus (WNV) circulating in mosquitos in Serbia, Southern Europe. Upon initial detection of unexpected product in a PCR protocol for partial WNV NS5 gene amplification, further confirmation and identification was obtained through additional PCR and Sanger sequencing experiments. Bioinformatic and phylogenetic analysis identified the obtained sequences as Xanthi chryso-like virus (XCLV). The finding is particular for the fact that it associates XCLV with a new potential vector species and documents a novel geographical area of its distribution.

Evolutionary dynamics of Usutu virus: Worldwide dispersal patterns and transmission dynamics in Europe.

Background: Usutu virus (USUV) is an emerging mosquito-borne Flavivirus, with birds as the main zoonotic reservoir. Humans are accidental hosts and mostly develop mild or even asymptomatic infections, although severe complications such as encephalitis can also arise. Detailed characterization of the pathogen's phylogenetics may offer valuable insights into the prediction and prevention of potential epidemics; however, lack of uniformity and the number of available USUV sequences worldwide hamper comprehensive investigation. Aim: The study aimed to investigate USUV spatio-temporal dispersal inter- and intracontinentally and to estimate the dynamics of viral spread within Europe. Methods: Phylogeographic and phylodynamic analyses were done using advanced phylogenetic methods implemented in Beast 1.10.4 and Beast 2.6.4 software packages. Results: Herein, we report on a new USUV isolate from Culex pipiens collected in 2019 from Serbia. The results of this research revealed two newly described intercontinental migration events of USUV from Africa to Germany in the 1970s and from Africa to the Middle East (Israel) in the late 90s. Finally, phylodynamic analysis substantiated the ongoing active expansion of USUV in Europe. Conclusion: The data would imply a high potential for further USUV expansion in Europe. Detailed phylogenetic characterization of the pathogen may offer valuable insights into prediction and prevention of potential epidemics; however, lack of uniformity and number of available USUV sequences worldwide hampers comprehensive investigation. This study draws attention to the need for upscaling USUV surveillance.

Cytomegalovirus infection may be oncoprotective against neoplasms of B-lymphocyte lineage: single-institution experience and survey of global evidence.

BACKGROUND: Although cytomegalovirus (CMV) is not considered tumorigenic, there is evidence for its oncomodulatory effects and association with hematological neoplasms. Conversely, a number of experimental and clinical studies suggest its putative anti-tumour effect. We investigated the potential connection between chronic CMV infection in patients with B-lymphocyte (B-cell) malignancies in a retrospective single-center study and extracted relevant data on CMV prevalences and the incidences of B-cell cancers the world over. METHODS: In the clinical single-center study, prevalence of chronic CMV infection was compared between patients with B-cell leukemia/lymphoma and the healthy controls. Also, global data on CMV seroprevalences and the corresponding country-specific incidences of B- lineage neoplasms worldwide were investigated for potential correlations. RESULTS: Significantly higher CMV seropositivity was observed in control subjects than in patients with B-cell malignancies (p = 0.035). Moreover, an unexpected seroepidemiological evidence of highly significant inverse relationship between country-specific CMV prevalence and the annual incidence of B-cell neoplasms was noted across the populations worldwide (ρ = -0.625, p < 0.001). CONCLUSIONS: We try to draw attention to an unreported interplay between CMV infection and B-cell lymphomagenesis in adults. A large-scale survey across > 70 countries disclosed a link between CMV and B-cell neoplasms. Our evidence hints at an antagonistic effect of chronic CMV infection against B-lymphoproliferation.

Factors Associated With Cytomegalovirus Infection in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Prospective Single-Center Study.

OBJECTIVES: The human cytomegalovirus is a notorious pathogen in the pediatric transplant setting. Although studies on factors in complicity with cytomegalovirus infection abound, the roles of age, sex, allogeneic hematopoietic stem cell transplant modality, and type of underlying disease (malignant vs nonmalignant) with regard to cytomegalovirus infection and viral load in children are seldom explored. Our aim was to examine the significance of these factors on cytomegalovirus infection and viral load in Serbian pediatric recipients of allogeneic hematopoietic stem cell transplant. MATERIALS AND METHODS: Thirty-two pediatric recipients of allogeneic hematopoietic stem cell transplant to treat various malignant and nonmalignant disorders were prospectively monitored for cytomegalovirus infection. The real-time quantitative polymerase chain reaction was used for pathogen detection and quantitation. Demographic and virologic parameters were statistically analyzed with SPSS statistics software (version 20). RESULTS: Cytomegalovirus DNA was detected in 23 patients (71.9%). Infection occurred significantly more often (P = .015) in patients with haploidentical donors. The opposite was noted for matched sibling grafts (P = .006). Viral load was higher in female patients (P = .041) and children with malignant diseases (P = .019).There was no significant relationship between viral infection or load and medical complications. CONCLUSIONS: Transplant recipients presented with a high incidence of cytomegalovirus viremia. The modality of allogeneic hematopoietic stem cell transplant was associated with the frequency of cytomegalovirus infection. Age, sex, type of underlying disease, and medically relevant events were not conducive to occurrences of viremia. Notably, we observed substantial viral loads in female patients and patients with neoplastic diseases. Studies comprising larger populations are needed to better understand these results.

Slight variations in coastal topography mitigate the consequence of storm-induced marine submersion on amphibian communities.

The rise in sea-level and the increase in frequency and intensity of extreme weather events (i.e., storms and associated surges) are expected to strongly impact coastal areas. The gradual impacts of sea-level rise may allow species to display adaptive responses to overcome environmental changes. In contrast, the abruptness of marine submersions during extreme weather events can induce changes that may exceed the ability of species to respond to brutally changing environments. Yet, site-specific topographical features may buffer the expected detrimental effects of marine submersions on wildlife. In order to test such topographical effects, we examined the long-term consequences of a major marine submersion (storm Xynthia) on the amphibian communities of two French Atlantic coastal wetlands that slightly differ in their topography and, thus, their susceptibility to marine submersion. Amphibians were monitored on 64 ponds for up to 13 years, using acoustic and visual methods, in conjunction with environmental parameters (e.g., pond topology, vegetation, salinity). We found that the amphibian communities at the two neighboring sites displayed different responses to the marine submersion linked to storm Xynthia. As predicted, slight differences in local topography induced strong differences in local magnitude of the landward marine surge, influencing salinization dynamics and associated consequences on wildlife (amphibians). The different species responses show that amphibian richness can recover to that of pre-storm conditions, but with significant changes in the composition of the community. Our results suggest that amphibian presence post-submersion in coastal wetlands results from an interaction between species traits (e.g., tolerance to elevated salinity), site-specific topography, and environmental parameters. Finally, our study emphasizes that relatively modest landscaping management may be critical to allow wildlife to successfully recover after a marine submersion.

Comparison of HPV detection rate in formalin-fixed paraffin-embedded tissues of head and neck carcinoma using two DNA extraction kits and three amplification methods.

The potential problems of DNA extraction from formalin-fixed paraffin-embedded (FFPE) tissue samples and amplification efficiency of Human papilloma virus (HPV) may occur in the molecular studies of head and neck squamous carcinoma (HNSCC). The aim of this study was to compare HPV detection rate in FFPE tissues of oral, oropharyngeal, hypopharyngeal, and laryngeal cancers using two silica-based extraction kits and three amplification methods. A total of 50 FFPE specimens from HNSCC tissues were analyzed. The quality and quantity of the extracted DNA were tested by spectrophotometry. HPV DNA was detected using a single polymerase chain reaction (PCR), a nested PCR, and a Real-time PCR kit. Statistically significantly higher DNA quality and quantity was observed using the QIAamp DNA FFPE Tissue Kit than when using the QIAamp DNA Mini Kit. There was not HPV amplification in any of the 50 FFPE samples using the single PCR and Real-time PCR kits, whereas HPV DNA was detected in 22% of samples using nested PCR. Comparing results of the three different methods showed that HPV DNA was detected only with nested PCR. The results presented imply that nested PCR is the most appropriate method for the detection of HPV DNA in FFPE samples, along with adequate DNA extraction methods.

Cytomegalovirus glycoprotein B and N genotypes in pediatric recipients of the hematopoietic stem cell transplant.

Clinical significance of the cytomegalovirus (CMV) genotypes in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) has been evaluated mostly in adults. The studies of diverse CMV glycoprotein B (gB) and N (gN) genotype variants in transplanted children and adolescents are lacking. We analyzed the investment of gB and gN genotype variants in the HSCTed children and their relation to clinical complications and disease outcome. The cohort included forty two pediatric recipients of the HSCT. Patients positive for CMV DNAemia (24/42, 57.1%) were genotyped. The gB4 and gN1 genotype variants predominated and were evidenced in 7/18 (38.9%) and 9/19 (47.4%) patients, respectively. The graft-versus-host disease (GvHD) predominated in children with viremia (p < 0.05). Frequencies of the gB and gN genotypes contrasted those reported in recent studies. The GvHD scaled strongly with CMV reactivation whereas viral loads were uncorrelated to medical complications and treatment outcomes.

A Dual Mode Adaptive Basal-Bolus Advisor Based on Reinforcement Learning.

Self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) are commonly used by type 1 diabetes (T1D) patients to measure glucose concentrations. The proposed adaptive basal-bolus algorithm (ABBA) supports inputs from either SMBG or CGM devices to provide personalised suggestions for the daily basal rate and prandial insulin doses on the basis of the patients' glucose level on the previous day. The ABBA is based on reinforcement learning, a type of artificial intelligence, and was validated in silico with an FDA-accepted population of 100 adults under different realistic scenarios lasting three simulated months. The scenarios involve three main meals and one bedtime snack per day, along with different variabilities and uncertainties for insulin sensitivity, mealtime, carbohydrate amount, and glucose measurement time. The results indicate that the proposed approach achieves comparable performance with CGM or SMBG as input signals, without influencing the total daily insulin dose. The results are a promising indication that AI algorithmic approaches can provide personalised adaptive insulin optimization and achieve glucose control-independent of the type of glucose monitoring technology.

Reinforcement Learning-Based Adaptive Insulin Advisor for Individuals with Type 1 Diabetes Patients under Multiple Daily Injections Therapy.

The existing adaptive basal-bolus advisor (ABBA) was further developed to benefit patients under insulin therapy with multiple daily injections (MDI). Three different in silico experiments were conducted with the DMMS.R simulator to validate the approach of combined use of self-monitoring of blood glucose (SMBG) and insulin injection devices, e.g. insulin pen, as are used by the majority of type 1 diabetes patients under insulin therapy. The proposed approach outperforms the conventional method, as it increases the time spent within the target range and simultaneously reduces the risks of hyperglycaemic and hypoglycaemic events.

MUM-1 and bcl-2 Positive Primary Diffuse Large B Cell Non-Hodgkin's Lymphoma of the Colon.

Primary diffuse large B cell lymphoma (DLBCL) presents as a nodal and extranodal disease. The most common extranodal site is the gastrointestinal tract (GI), with the stomach most frequently involved, followed by the small bowel. Primary DLBCL of the large bowel accounts for 0.2%-1.2% of all colonic tumors. We present two patients who underwent radical resections of right colonic tumors. They were diagnosed with primary colonic DLBCL following histological and immunohistochemical testing of the excised tissues, and were determined as being in stage IIE of the disease. The tumors expressed CD20 markers. Both received multi-agent chemotherapy with combined immunotherapy and remain in complete remission at 4 and 5 years.

Automated estimation of the truncation of room impulse response by applying a nonlinear decay model.

Noise represents one of the most significant disturbances in measured room impulse responses (RIRs), and it has a potentially large impact on evaluation of the decay parameters. In order to reduce noise effects, various methods have been applied, including truncation of an RIR. In this paper, a procedure for the response truncation based on a model of RIR (nonlinear decay model) is presented. The model is represented by an exponential decay plus stationary noise. Unknown parameters of the model are calculated by an optimization that minimizes the difference between the curve generated by the model and the target one of the response to be truncated. Different curves can be applied in the optimization-absolute value of the RIR, logarithmic decay curve, and Schroeder curve obtained by the backward integration of the RIR. The proposed procedure is tested on various synthesized and measured impulse responses. It is compared with the procedure taken from the literature, often applied in practice.

Frequency of REM sleep behavior disorders in patients with Parkinson's disease.

BACKGROUND/AIM: Sleep is prompted by natural cycles of activity in the brain and consists of two basic states: rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. REM sleep behavior disorder (RBD) is characterized by violent motor and vocal behavior during REM sleep which represents dream enactment. The normal loss of muscle tone, with the exception of respiratory, sphincter, extra ocular and middle ear muscles, is absent in patients with RBD. The origin of RBD is frequently unknown, but can be associated with degenerative neurological disorders, such as Parkinson's disease (PD). PD patients do not necessarily express features of RBD, which is identified in approximately third to a half of them. The aim of this study was to estimate the prevalence of RBD in a cohort of PD patients, as well as to identify risk-factors for its development. METHODS: In the period from December 2010 to September 2011 we recruited 97 consecutive PD outpatients, treated in the Institute of Neurology, Clinical Center of Serbia, Belgrade. After establishing the diagnosis, all the patients filled out a specially constructed questionnaire with the following items: actual age, sex, age at disease onset, disease duration, form of the disease, type of treatment, duration of treatment, the presence of constipation, lessening of smell sense, and family history of PD. At entring the study, patients disability was scored using the Unified Parkinson's Disease Rating Scale (motor part - UPDRS). Cognitive abilities were assessed by the Mini Mental Status Examination (MMSE) scale, and depression symptoms by the 21-item Hamilton Depression Rating Scale (HDRS). The patients with PD were dichotomized to those with and without RBD using the RBD Questionnaire-Hong Kong (RBDQ-HK) in the manner of an interview. Forms of PD, mode of treatment, sex, constipation and family history were investigated using the Fishers χ2 test. Symptoms and treatment duration, the presence of smell disturbances, MMSE score, UPDRS motor score and HDRS score were analyzed by implementation of the Z-test. Actual age and age at disease onset were evaluated by the unpaired t-test. RESULTS: The RBD-positive group contained 15 (15.5%) patients, while in the rest of them (82/97), RBD was not identified (nonRBD group). There was no difference between the two groups considering gender distribution (p = 0.847), age (p = 0.577), age at disease onset (p = 0.141 ), duration. of PD (p = 0.069), family history (p = 0.591), type of initial symptoms (p = 0.899), constipation (p = 0.353), olfaction (p = 0.32) and MMSE scores (p = 0.217). The duration of treatment in the RBD group was longer than in the non-RBD group (9.4 ± 5.3 and 6.3 ± 3.9 years, respectively; p = 0.029), and the UPDRS motor score in the RBD group was higher (19.1 ± 9.4 and 12.7 ± 8.2, respectively; p = 0.013). Also, HDRS scores were higher in patients expressing RBD (10.1 ± 6.0 and 6.4 ± 4.5, respectively; p = 0.019). CONCLUSION: We found that 15.5% of the consecutive PD patients had RBD, and that the patients with RBD differed from the non-RBD ones regarding duration of treatment, disease and depressive symptoms severity.

Modulated Hebb-Oja learning rule--a method for principal subspace analysis.

This paper presents analysis of the recently proposed modulated Hebb-Oja (MHO) method that performs linear mapping to a lower-dimensional subspace. Principal component subspace is the method that will be analyzed. Comparing to some other well-known methods for yielding principal component subspace (e.g., Oja's Subspace Learning Algorithm), the proposed method has one feature that could be seen as desirable from the biological point of view--synaptic efficacy learning rule does not need the explicit information about the value of the other efficacies to make individual efficacy modification. Also, the simplicity of the "neural circuits" that perform global computations and a fact that their number does not depend on the number of input and output neurons, could be seen as good features of the proposed method.