Loneliness in OCD and its determinants.

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and repetitive behaviors, affecting approximately 1.3 % of the population. Loneliness has serious consequences for future health outcomes. Although it has been extensively studied in depression, its prevalence in obsessive-compulsive disorder (OCD) has hardly been investigated. The current study sought to examine the association between loneliness and OCD, through an exploratory investigation of their demographic and clinical correlates. This cross-sectional study utilized data from the Netherlands Obsessive-Compulsive Disorder Association (NOCDA) study, designed to investigate determinants, course, and consequences of OCD in a large clinical sample. In this data base, a cohort of 363 OCD adult patients underwent assessment for loneliness severity, OCD symptomatology, comorbid conditions, and demographic variables. Findings reveal a high prevalence of loneliness among OCD patients, with nearly three-quarters (73.6 %) experiencing elevated levels. Loneliness was associated with greater depression severity and specific demographic factors such as gender, age, and education level. However, the relationship between OCD severity and loneliness was explained by depression severity. Clinical and theoretical implications are discussed as well as limitations and directions for future research.

Early Screening for the Parkinson Variant of Multiple System Atrophy: A 6-Item Score.

BACKGROUND: A 4-item score based on ≥2 features out of orthostatic hypotension, overactive bladder, urinary retention and postural instability was previously shown to early distinguish the Parkinson-variant of multiple system atrophy (MSA-P) from Parkinson's disease (PD) with 78% sensitivity and 86% specificity. OBJECTIVES: To replicate and improve the 4-item MSA-P score. METHODS: We retrospectively studied 161 patients with early parkinsonism [ie, ≤2 years disease duration or no postural instability, aged 64 (57; 68) years, 44% females] and a diagnosis of clinically established MSA-P (n = 38) or PD (n = 123) after ≥24 months follow-up. RESULTS: The 4-item MSA-P score had a 92% sensitivity and 78% specificity for a final MSA-P diagnosis. By including dopaminergic responsiveness and postural deformities into a 6-item score (range: 0-6), reaching ≥3 points at early disease identified MSA-P patients with 89% sensitivity and 98% specificity. CONCLUSIONS: The 6-item MSA-P score is a cost-effective tool to pinpoint individuals with early-stage MSA-P.

Multidisciplinary intensive outpatient rehabilitation program for patients with moderate-to-advanced Parkinson's disease.

BACKGROUND: Intensive, multi-disciplinary, rehabilitation programs for patients with Parkinson's disease (PWPs) have shown to be effective. However, most programs are based on in-patient service, which is expensive. OBJECTIVE: To demonstrate the feasibility of a multidisciplinary, intensive, outpatient rehabilitation program (MIOR) for moderate to advanced Parkinson's Disease (H&Y≥2). METHOD: The MIOR program takes place at a community rehabilitation center ('Ezra Le'Marpe'), 3 times a week, 5 hours, 8 weeks, and includes 20 PWPs in each cycle. The multi-disciplinary team includes physical, occupational, speech and hydro therapists. Additional activities include, social work groups, boxing, dancing and bridge. RESULTS: Data was collected retroactively for the first two years. Data analysis includes 158 patient files who completed the program (mean disease duration 10.1±6 and mean H&Y stage 2.8±0.67). Assessments were performed at the beginning and end of the intervention. Positive results were collected: improvement in number of falls (p < 0.0001), Functional Independence Measure (p < 0.0001), quality of life (p < 0.01), balance (p < 0.0001), upper limb function (p < 0.0001) and paragraph reading vocal intensity (p < 0.01). CONCLUSIONS: MIOR is a feasible program, showing positive results in moderate to advanced PWP's, improving quality of life, daily function, and motor performance. The current outcomes demonstrate feasibility of MIOR in addition to medical treatment.

Validation of the Hebrew Version of the Unified Dyskinesia Rating Scale.

BACKGROUND: The Unified Dyskinesia Rating Scale (UDysRS) is a well-established tool for producing comprehensive assessments of severity and disability associated with dyskinesia in patients with Parkinson's disease (PD). The scale was originally developed in English, and a broad international effort has been undertaken to develop and validate versions in additional languages. Our aim was to validate the Hebrew version of the UDysRS. METHODS: We translated the UDysRS into Hebrew, back-translated it into English, and carried out cognitive pretesting. We then administered the scale to non-demented native Hebrew-speaking patients who fulfilled the Brain Bank diagnostic criteria for probable PD (n = 250). Data were compared to the Reference Standard data used for validating UDysRS translations. RESULTS: The different portions of the Hebrew UDysRS showed high internal consistency (α ≥ 0.92). A confirmatory factor analysis in which we compared the Hebrew UDysRS to the Reference Standard version produced a comparative fit index (CFI) of 0.98, exceeding the threshold criterion of CFI > 0.9 indicating factor validity. A secondary exploratory factor analysis provided further support to the consistency between the factor structures of the Hebrew and Reference Standard versions of the UDysRS. CONCLUSION: The UDysRS Hebrew version shows strong clinimetric properties and fulfills the criteria for designation as an official International Parkinson and Movement Disorder Society-approved translation for use in clinical and research settings.

Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication.

Viruses are known for their extremely compact genomes composed almost entirely of protein-coding genes. Nonetheless, four long noncoding RNAs (lncRNAs) are encoded by human cytomegalovirus (HCMV). Although these RNAs accumulate to high levels during lytic infection, their functions remain largely unknown. Here, we show that HCMV-encoded lncRNA4.9 localizes to the viral nuclear replication compartment, and that its depletion restricts viral DNA replication and viral growth. RNA4.9 is transcribed from the HCMV origin of replication (oriLyt) and forms an RNA-DNA hybrid (R-loop) through its G+C-rich 5' end, which may be important for the initiation of viral DNA replication. Furthermore, targeting the RNA4.9 promoter with CRISPR-Cas9 or genetic relocalization of oriLyt leads to reduced levels of the viral single-stranded DNA-binding protein (ssDBP), suggesting that the levels of ssDBP are coupled to the oriLyt activity. We further identified a similar, oriLyt-embedded, G+C-rich lncRNA in murine cytomegalovirus (MCMV). These results indicate that HCMV RNA4.9 plays an important role in regulating viral DNA replication, that the levels of ssDBP are coupled to the oriLyt activity, and that these regulatory features may be conserved among betaherpesviruses.

Validation of the Hebrew version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale.

BACKGROUND: The Movement Disorders Society (MDS) published the English new Unified Parkinson's Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson's disease (PD) in 2008. We aimed to validate the Hebrew version of the MDS-UPDRS, explore its dimensionality and compare it to the original English one. METHODS: The MDS-UPDRS questionnaire was translated to Hebrew and was tested on 389 patients with PD, treated at the Movement Disorders Unit at Tel-Aviv Medical Center. The MDS-UPDRS is made up of four sections. The higher the score, the worst the clinical situation of the patient is. Confirmatory and explanatory factor analysis were applied to determine if the factor structure of the English version could be confirmed in the Hebrew version. RESULTS: The Hebrew version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Hebrew-version was satisfactory, with Cronbach's alpha values 0.79, 0.90, 0.93, 0.80, for parts 1 to 4 respectively. In the confirmatory factor analysis, all four parts had high (greater than 0.90) comparative fit index (CFI) in comparison to the original English MDS-UPDRS with high factor structure (0.96, 0.99, 0.94, 1.00, respectively), thus confirming the pre-specified English factor structure. Explanatory factor analysis yielded that the Hebrew responses differed from the English one within an acceptable range: in isolated item differences in factor structure and in the findings of few items having cross loading on multiple factors. CONCLUSIONS: The Hebrew version of the MDS-UPDRS meets the requirements to be designated as the Official Hebrew Version of the MDS-UPDRS.

Head-up tilt testing for detecting orthostatic hypotension: how long do we need to wait?

BACKGROUND: Orthostatic hypotension (OH) is a common underdiagnosed condition characterized by a fall in systolic or diastolic blood pressure (BP). There is some uncertainty about the minimum duration needed to detect OH beyond 3 min (delayed OH). We aimed to define a minimum time range for measurement of delayed OH in subjects referred to as tilt testing. METHODS: A repeated measurements study Tel-Aviv Medical Center, on 692 subjects who underwent prolonged (40 min, vertical position) drug-free tilt testing. Survival curves were used to study time to an OH event; logistic regression to study factors associated with delayed OH and mixed models to study the pattern of repeated BP measures. RESULTS: In our sample, 17% had OH within 3 min, 35% within 30 min, and 40% within 40 min. Among the 270 OH patients, 43 and 91% were identified within 3 and 30 min, respectively. Delayed OH was associated with female gender (OR = 1.95, 1.16-3.27) and age <65 years (OR = 2.17, 1.24-3.80). Older patients differed significantly from younger patients in BP pattern changes and had a higher rate of a fall in systolic BP. CONCLUSION: Tilt testing for 30 min identifies most cases of delayed OH in older patients, while those younger than 65 years need 10 min longer.

Modulating oscillatory brain activity correlates of behavioral inhibition using transcranial direct current stimulation.

OBJECTIVE: Studies have mainly documented behavioral changes induced by transcranial direct current stimulation (tDCS), but recently cortical modulations of tDCS have also been investigated. Our previous work revealed behavioral inhibition modulation by anodal tDCS over the right inferior frontal gyrus (rIFG); however, the electrophysiological correlates underlying this stimulation montage have yet to be established. The current work aimed to evaluate the distribution of neuronal oscillations changes following anodal tDCS over rIFG coupled with cathodal tDCS over left orbitofrontal cortex (lOFC) using spectral power analysis. METHODS: Healthy subjects underwent sham and real tDCS (15 min, 1.5 mA, anodal rIFG; cathodal lOFC) stimulation conditions in a single-blind, placebo-controlled cross-over trial. Following tDCS session, resting EEG recordings were collected during 15 min. RESULTS: Analysis showed a significant and selective diminution of the power of theta band. The theta diminution was observed in the rIFG area (represented the anode electrode), and was not found in the lOFC area (represented the cathode electrode). A significant effect was observed only in the theta but not in other bands. CONCLUSIONS: These results are the first demonstration of modulating oscillatory activity as measured by EEG with tDCS over rIFG in general, and documenting theta band reduction with this montage in particular. SIGNIFICANCE: Our results may explain the improvement in behavioral inhibition reported in our previous work, and although this study was conducted with healthy subjects, the findings suggest that tDCS may also modulate electrophysiological changes among ADHD patients, where decreasing theta activity is the target of neuro-feedback methods aimed to improve cognitive control.