Transcranial Magnetic Stimulation Measures, Pyramidal Score on Expanded Disability Status Scale and Magnetic Resonance Imaging of Corticospinal Tract in Multiple Sclerosis.

Probing the cortic ospinal tract integrity by transcranial magnetic stimulation (TMS) could help to understand the neurophysiological correlations of multiple sclerosis (MS) symptoms. Therefore, the study objective was, first, to investigate TMS measures (resting motor threshold-RMT, motor evoked potential (MEP) latency, and amplitude) of corticospinal tract integrity in people with relapsing-remitting MS (pwMS). Then, the study examined the conformity of TMS measures with clinical disease-related (Expanded Disability Status Scale-EDSS) and magnetic resonance imaging (MRI) results (lesion count) in pwMS. The e-field navigated TMS, MRI, and EDSS data were collected in 23 pwMS and compared to non-clinical samples. The results show that pwMS differed from non-clinical samples in MEP latency for upper and lower extremity muscles. Also, pwMS with altered MEP latency (prolonged or absent MEP response) had higher EDSS, general and pyramidal, functional scores than pwMS with normal MEP latency finding. Furthermore, the RMT intensity for lower extremity muscles was predictive of EDSS functional pyramidal scores. TMS/MEP latency findings classified pwMS as the same as EDSS functional pyramidal scores in 70-83% of cases and were similar to the MRI results, corresponding to EDSS functional pyramidal scores in 57-65% of cases. PwMS with altered MEP latency differed from pwMS with normal MEP latency in the total number of lesions in the brain corticospinal and cervical corticospinal tract. The study provides preliminary results on the correspondence of MRI and TMS corticospinal tract evaluation results with EDSS functional pyramidal score results in MS.

Gaia as Solaris: An Alternative Default Evolutionary Trajectory.

Now that we know that Earth-like planets are ubiquitous in the universe, as well as that most of them are much older than the Earth, it is justified to ask to what extent evolutionary outcomes on other such planets are similar, or indeed commensurable, to the outcomes we perceive around us. In order to assess the degree of specialty or mediocrity of our trajectory of biospheric evolution, we need to take into account recent advances in theoretical astrobiology, in particular (i) establishing the history of habitable planets' formation in the Galaxy, and (ii) understanding the crucial importance of "Gaian" feedback loops and temporal windows for the interaction of early life with its physical environment. Hereby we consider an alternative macroevolutionary pathway that may result in tight functional integration of all sub-planetary ecosystems, eventually giving rise to a true superorganism at the biospheric level. The blueprint for a possible outcome of this scenario has been masterfully provided by the great Polish novelist Stanislaw Lem in his 1961 novel Solaris. In fact, Solaris offers such a persuasive and powerful case for an "extremely strong" Gaia hypothesis that it is, arguably, high time to investigate it in a discursive astrobiological and philosophical context. In addition to novel predictions in the domain of potentially detectable biosignatures, some additional cognitive and heuristic benefits of studying such extreme cases of functional integration are briefly discussed.

Psychometric Properties of the Pittsburgh Sleep Quality Index (PSQI) in Patients with Multiple Sclerosis: Factor Structure, Reliability, Correlates, and Discrimination.

Sleep disturbances and poor sleep are a common complaint in the population with multiple sclerosis (MS) disease. The most commonly reported scale is the Pittsburgh Sleep Quality Index (PSQI), measuring seven components of sleep quality. Yet, till today, the PSQI instrument has not been validated in people with multiple sclerosis (pwMS). The objective of our study was to add precision in sleep quality assessment by investigating the psychometric properties of PSQI (factor structure, reliability, validity based on relations with other variables, cut-off scores) in pwMS. The cross-sectional study included data on a total of 87 patients with MS and 216 control subjects. Demographic information, education level, and MS-related variables were ascertained. Psychometric properties were examined by estimating the validity, including factor structure, metric invariance, and relations with other MS- and non-MS-related variables, reliability, and discrimination ability of the PSQI. The Croatian version of the PSQI had a two-factor structure which demonstrated loading and partial intercept invariance between pwMS and the control group. The global score and both subscales had high internal consistencies (McDonald's omega and Cronbach's alpha coefficients) in pwMS and showed expected relations with demographic and MS-related variables. PwMS differed significantly in the PSQI global score from the control groups, although receiver operating characteristics (ROC) curve analysis did not indicate a clear cut-off point. The PSQI is a reliable and valid scale and can be applied in clinical settings for assessing sleep quality in pwMS.

Validation of the fatigue severity scale in Croatian population of patients with multiple sclerosis disease: Factor structure, internal consistency, and correlates.

BACKGROUND: Fatigue is a common symptom in people with multiple sclerosis (MS) and is evaluated and monitored with self-report questionnaires. The objective of this study was to determine the psychometric properties of the Croatian version of the Fatigue Severity Scale (FSS) in people with MS. MATERIAL AND METHODS: This is a retrospective cohort study conducted as an online survey from December 16, 2020, until January 13, 2021. A total of 179 people with MS and 999 control subjects completed FSS and self-administered questionnaires capturing information of demographic, education level, disease-related variables (duration of the disease, MS type, the expanded disability status scale (EDSS), and Multiple Sclerosis Impact Scale-29 (MSIS-29). Psychometric properties were examined by estimating the validity, reliability, and factor structure of the FSS scale in people with MS. RESULTS: The Croatian version of the FSS had excellent internal consistency (Cronbach's α value 0.93). Factor analysis demonstrated a unidimensional structure. The concurrent validity of the FSS appeared to be satisfactory due to the significant differences between people with MS and control subjects (p < .05). The correlations between FSS and MSIS-29 physical (r = 0.60) and psychological (r = 0.50) subscale results confirmed the convergent validity of the FSS scale. Results also indicated that the best cut-off score is between 4 and 5 with a relatively high sensitivity and specificity. CONCLUSIONS: The Croatian version of FSS was shown to have excellent psychometric properties in people with MS and can be used in the research and clinical settings evaluating fatigue in people with MS in Croatia.

Information Processing Speed Assessed with Letter Digit Substitution Test in Croatian Sample of Multiple Sclerosis Patients.

Cognitive impairment is a common complaint in people with multiple sclerosis (pwMS). The study objective was to determine the psychometric properties of the letter digit substitution test (LDST) that measures information processing speed and to investigate the impact of relevant predictors of LDST achievement in pwMS. The design was cross-sectional. The study included 87 pwMS and 154 control subjects. The validity of LDST was examined, and a hierarchical regression model was used to explore relevant predictors of LDST success. The LDST had excellent construct validity, as expressed by differences between pwMS and control subjects. Convergent validity of the LDST was supported by a significant moderate correlation with the expanded disability status scale (EDSS) (ρ = -0.36; p < 0.05) and a significantly strong correlation with the multiple sclerosis impact scale (MSIS-29) physical subscale (r = -0.64; p < 0.01). The LDTS score well differentiated the pwMS considering age, education, EDSS, disease duration, comorbidity, and medication therapy. Using the LDST as a criterion variable in pwMS results showed consistent evidence for the age, education, and EDSS impact on LDST performance. The best cut-off score of ≤35 discriminated the control and MS group. LDST proved to be a valid test for assessing information processing speed in pwMS.

Psychometric Properties of the HADS Measure of Anxiety and Depression Among Multiple Sclerosis Patients in Croatia.

Depression and anxiety are common complaints in patients with multiple sclerosis (MS). The study objective was to investigate the factor structure, internal consistency, and correlates of the Croatian version of the Hospital Anxiety and Depression Scale (HADS) in patients with MS. A total of 179 patients with MS and 999 controls were included in the online survey. All subjects completed the HADS and self-administered questionnaires capturing information of demographic, education level, disease-related variables, and the Multiple Sclerosis Impact Scale-29 (MSIS-29). Psychometric properties were examined by estimating the validity, reliability, and factor structure of the HADS in patients with MS. The two HADS subscales (anxiety and depression) had excellent internal consistencies (Cronbach's α value 0.82-0.83), and factor analysis confirmed a two-factor structure. The convergent validity of the HADS subscales appeared to be good due to the significant correlations between HADS and MSIS-29. Receiver operating characteristic (ROC) analysis indicates that the HADS subscales have a significant diagnostic validity for group differentiation. Hierarchical regression analysis using MSIS-29 subscales as criterion variables showed consistent evidence for the incremental validity of the HADS. The HADS is a reliable and valid self-assessment scale in patients with MS and is suggested to be used in clinical monitoring of the psychiatric and psychological status of patients with MS.

CONCURRENT DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM ASSOCIATED WITH HYPERTHYROIDISM: A CASE REPORT.

Numerous disorders of coagulation and fibrinolysis have been reported in patients with thyroid diseases, especially with hyperthyroidism. Most articles are focused on deep vein thrombosis risk, however, few of them describe association between hyperthyroidism and pulmonary embolism. We report a case of a 43-year-old woman with long-term uncontrolled hyperthyroidism complicated by venous thromboembolism. The potential mechanisms could be endothelial dysfunction, decreased fibrinolytic activity, and increased levels of coagulation factors. Thyroid evaluation should be recommended in patients with unprovoked venous thromboembolic events.

Dictyostelium Dynamin Superfamily GTPases Implicated in Vesicle Trafficking and Host-Pathogen Interactions.

The haploid social amoeba Dictyostelium discoideum is a powerful model organism to study vesicle trafficking, motility and migration, cell division, developmental processes, and host cell-pathogen interactions. Dynamin superfamily proteins (DSPs) are large GTPases, which promote membrane fission and fusion, as well as membrane-independent cellular processes. Accordingly, DSPs play crucial roles for vesicle biogenesis and transport, organelle homeostasis, cytokinesis and cell-autonomous immunity. Major progress has been made over the last years in elucidating the function and structure of mammalian DSPs. D. discoideum produces at least eight DSPs, which are involved in membrane dynamics and other processes. The function and structure of these large GTPases has not been fully explored, despite the elaborate genetic and cell biological tools available for D. discoideum. In this review, we focus on the current knowledge about mammalian and D. discoideum DSPs, and we advocate the use of the genetically tractable amoeba to further study the role of DSPs in cell and infection biology. Particular emphasis is put on the virulence mechanisms of the facultative intracellular bacterium Legionella pneumophila.

Protein Phosphatase 1 Regulates Human Cytomegalovirus Protein Translation by Restraining AMPK Signaling.

Human cytomegalovirus (HCMV) carries the human protein phosphatase 1 (PP1) and other human proteins important for protein translation in its tegument layer for a rapid supply upon infection. However, the biological relevance behind PP1 incorporation and its role during infection is unclear. Additionally, PP1 is a difficult molecular target due to its promiscuity and similarities between the catalytic domain of multiple phosphatases. In this study, we circumvented these shortcomings by using 1E7-03, a small molecule protein-protein interaction inhibitor, as a molecular tool of noncatalytic PP1 inhibition. 1E7-03 treatment of human fibroblasts severely impaired HCMV replication and viral protein translation. More specifically, PP1 inhibition led to the deregulation of metabolic signaling pathways starting at very early time points post-infection. This effect was at least partly mediated by the prevention of AMP-activated protein kinase dephosphorylation, leading to elongation factor 2 hyperphosphorylation and reduced translation rates. These findings reveal an important mechanism of PP1 for lytic HCMV infection.

Quorum sensing governs a transmissive Legionella subpopulation at the pathogen vacuole periphery.

The Gram-negative bacterium Legionella pneumophila is the causative agent of Legionnaires' disease and replicates in amoebae and macrophages within a distinct compartment, the Legionella-containing vacuole (LCV). The facultative intracellular pathogen switches between a replicative, non-virulent and a non-replicating, virulent/transmissive phase. Here, we show on a single-cell level that at late stages of infection, individual motile (PflaA -GFP-positive) and virulent (PralF - and PsidC -GFP-positive) L. pneumophila emerge in the cluster of non-growing bacteria within an LCV. Comparative proteomics of PflaA -GFP-positive and PflaA -GFP-negative L. pneumophila subpopulations reveals distinct proteomes with flagellar proteins or cell division proteins being preferentially produced by the former or the latter, respectively. Toward the end of an infection cycle (˜ 48 h), the PflaA -GFP-positive L. pneumophila subpopulation emerges at the cluster periphery, predominantly escapes the LCV, and spreads from the bursting host cell. These processes are mediated by the Legionella quorum sensing (Lqs) system. Thus, quorum sensing regulates the emergence of a subpopulation of transmissive L. pneumophila at the LCV periphery, and phenotypic heterogeneity underlies the intravacuolar bi-phasic life cycle of L. pneumophila.

Combining proteomics and lipid analysis to unravel Confidor stress response in Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae is a useful model for studying the influence of different stress factors on eukaryotic cells. In this work we used the pesticide imidacloprid, in the Confidor formulation, as the stress factor and analyzed its influence on the metabolic activity, proteome and lipid content and composition of Saccharomyces cerevisiae yeast. During the cultivation of yeast, the lowest recommended application dose of Confidor (0.025%, v/v) was added to the growth media and its influence on the mitochondria, cytosol with microsomes, and the whole yeast cells was monitored. The results show that under the stress provoked by the toxic effects of Confidor, yeast cells density significantly decreased and the percentage of metabolically disturbed cells significantly increased comparing with untreated control. Also, there was a downregulation of majority of glycolytic, gluconeogenesis, and TCA cycle enzymes (Fba1, Adh1, Hxk2, Tal1, Tdh1,Tdh3, Eno1) thus providing enough acetyl-CoA for the lipid restructuring and accumulation mechanism since we have found the changes in the cell and mitochondrial lipid content and FA composition. This data suggest that lipids could be the molecules that orchestrate the answer of the cells in the stress response to the Confidor treatment.

The Event-related Potential P300 in Patients with Migraine.

OBJECTIVE: Recording of event-related potentials by using oddball paradigm of auditory P300 has yielded conflicting results in migraine. The aim of this study was to demonstrate that migraine patients have reduced P300 amplitude and prolonged P300 latency, suggesting alterations of the cognitive-evaluative component. METHODS: We recruited 29 migraine patients (24 females; median age 40 years) and 29 healthy age- and gender-matched participants. Participants were subjected to the same testing procedures of auditory P300 by discrimination the target auditory stimulus from the frequent stimulus, and analyzing P300 target/frequent stimulus amplitudes, and P300 target/frequent stimulus latencies. RESULTS: Patients with migraine don't have prolonged P300 target stimulus latency, but have a longer P300 frequent stimulus latency for 17.5ms. Out of 29 participants with migraine 8 had pathological P300 target stimulus amplitude, and 19 had pathological P300 frequent stimulus amplitude. CONCLUSION: People with migraine have altered the P300 which indicates the presence of cognitive dysfunction in these patients and importance of early diagnosis and intervention to preventing any deterioration in cognitive functions.