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Background Objective Methods Results Conclusions Tremor in Parkinson's disease (PD) is commonly regarded as less responsive to levodopa than bradykinesia and rigidity, with levodopa‐resistant PD tremor considered relatively common.The aim was to assess the levodopa responsiveness of tremor, bradykinesia, and rigidity in a population with advanced PD.We performed a retrospective study of 526 people with PD screened for deep brain stimulation.Levodopa's Cohen's d effect sizes were in the same order of magnitude for the 3 cardinal motor symptoms. Proportional improvement in tremor (86.8%) was higher than bradykinesia (45.7%) and rigidity (67.0%) (P < 0.0001). Full resolution was more frequent for tremor (67.9%) than for bradykinesia (0.4%) or rigidity (24.8%) (P < 0.0001). Levodopa‐unresponsive tremor, defined as improvement less than 25%, was documented only in 4.0%, as opposed to 19.4% for bradykinesia and 9.8% for rigidity (P < 0.0001).In advanced PD, tremor was more responsive to levodopa than bradykinesia and rigidity, and levodopa‐unresponsive tremor was relatively rare. [ABSTRACT FROM AUTHOR]

Background: The dopamine transporter striatal binding ratio (DAT SBR) has been used as an outcome measure in Parkinson's disease (PD) trials of potential disease‐modifying therapies; however, both patient characteristics and analysis approach potentially complicate its interpretation. Objective: The aim was to explore how well DAT SBR reflects PD motor severity across different striatal subregions and the relationship to disease duration, and side of onset. Methods: DAT SBR for the anterior and posterior putamen and caudate in both hemispheres was obtained using validated automated quantitative software on baseline scans of 132 patients recruited for the Exenatide PD2 and PD3 trials. Associations between mean and lateralized SBR subregions (posterior and anterior putamen and caudate) and summed and lateralized motor characteristics were explored using regression analysis. Analyses were repeated considering disease duration and limiting analysis to the less‐affected hemisphere. Results: Lateralized bradykinesia was most consistently associated with the loss of DAT uptake in the contralateral anterior putamen. There was much higher variance in the posterior putamen, and in all regions in those with longer duration disease, although bradykinesia remained robustly associated with anterior putaminal DAT uptake even in longer‐duration patients. Restricting analyses to the less‐affected side did not usefully reduce the variance compared to the overall cohort. Conclusion: These data suggest that DAT SBR could be a useful biomarker in disease‐modifying trials, but a focus on anterior striatal subregions and incorporating disease duration into analyses may improve its utility. [ABSTRACT FROM AUTHOR]

We have previously discovered that the selective activation of metabotropic glutamate type 2 receptors (mGluR2) and concurrent stimulation of metabotropic glutamate types 2 and 3 receptors (mGluR2/3) enhance the anti-parkinsonian action of l-3,4-dihydroxyphenylalanine (L-DOPA). Here, we sought to determine the effects of the mGluR2/3 orthosteric agonists LY-354,740 and LY-404,039, as well as the effects of the mGluR2 positive allosteric modulators LY-487,379 and CBiPES on the range of movement, bradykinesia, posture and alertness as adjuncts to L-DOPA. Ten 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmosets entered 4 experimental streams: L-DOPA + LY-354,740 (vehicle, 0.1, 0.3 and 1 mg/kg), L-DOPA + LY-404,039 (vehicle, 0.1, 1 and 10 mg/kg), L-DOPA + LY-487,379 (vehicle, 0.1, 1 and 10 mg/kg), L-DOPA + CBiPES (vehicle, 0.1, 1 and 10 mg/kg). For each molecule, treatments were randomised, and the range of movement, bradykinesia, posture and alertness were assessed by a blinded rater. None of the tested compounds significantly altered the global range of movement. LY-404,039 and CBiPES both reduced global bradykinesia, by up to 46% (both P < 0.05). LY-354,740, LY-404,039 and CBiPES each improved global posture by 35%, 44% and 39% (each P < 0.05), respectively. LY-404,039 and CBiPES both enhanced alertness by 54% (P < 0.05) and 79% (P < 0.01), respectively. LY-487,379 did not improve any of the parameters. Our results suggest that selective mGluR2 positive allosteric modulation and combined mGluR2/3 orthosteric stimulation might benefit bradykinesia, posture and alertness in PD when added to L-DOPA, which potentially represent novel therapeutic indications for molecules acting via these mechanisms. [ABSTRACT FROM AUTHOR]

Bradykinesia is one of the main symptoms to diagnose Parkinson's disease (PD). It indicates the slowness in the movement and can be measured using various upper-limb and lower-limb activities based on Unified Parkinson's Disease Rating Scale. The objective methods using machine learning techniques can provide an objective assessment of bradykinesia which solves the problem of inter-rater inconsistency. In this paper, we have proposed a new Repetitive Pointing Task (RPT activity) to assess upper-limb bradykinesia. The data is taken from 17 PD + 9 healthy controls who performs RPT activity and data is collected using a 3D motion capture system. New features are calculated based on characteristics of bradykinesia and RPT activity. With only six features, our method achieved an accuracy of 97.14%, the sensitivity of 97%, the specificity of 95%, the precision of 97%, and the F1-score of 97%. We have also found the relation between RPT based features and stage estimation based on the Hoehn and Yahr scale. When compared with state-of-the-art upper limb exercises, the proposed method performs significantly better in terms of accuracy i.e., increment of 1.791% with hand grasping, 4.14% with finger tapping, 6.34% with hand clasping and 8.84% with pronation/supination activity. There is also improvement in terms of effort and time required to perform the activity as it is a simple activity that can estimate bradykinesia on both sides of the body in one single sitting of just 17.5s. There is also improvement in terms of reliability of data collection process due to its non-invasiveness. The proposed method can also estimate PD stages without additional parameters. [ABSTRACT FROM AUTHOR]

Objective: To determine whether an accelerated protocol of 48 Hz cerebellar repetitive transcranial magnetic stimulation results in improved motor function in individuals with Parkinson's disease. Methods: In this double‐blind randomized sham‐controlled study, 35 individuals with Parkinson's disease and stable medical treatment were randomized to either sham or verum transcranial magnetic stimulation. The stimulation was applied bilaterally and medial over the cerebellum and comprised a novel accelerated protocol encompassing two sessions per day on 5 consecutive days. Patients were assessed at baseline, on day 5 after the last stimulation and 1 month post intervention. Measurements included dynamic posturography, UPDRS III, 8‐Meter walk test, and Timed Up and Go test. Results: The accelerated protocol was safe and feasible in an outpatient setting. Patients in the verum group showed significant improvement (p < 0.001) of motor symptoms as measured in the UPDRS III. Improvement was mainly carried by the domains rigor, bradykinesia, and gait and persisted after 1 month (p = 0.009), whereas tremor remained unchanged. Interpretation: The effect of a high‐dose transcranial magnetic stimulation in patients with Parkinson's disease is encouraging and comparable to other studies using much longer stimulation protocols. This short‐term intervention of 5 days facilitates the future application in an outpatient setting. Reduction in hospitalization rates directly benefits patients with motor impairment. [ABSTRACT FROM AUTHOR]

Background and Purpose: The article's significance lies in the substantial rise in the risk of developing Parkinson's disease (PD), necessitating the exploration of various approaches to rehabilitation and medical treatment. The purpose of the article is to detect the direct effect of physiotherapy for patients with PD and to identify how it helps in slowing down cardio‐pulmonary failure, improving the posture, balance, bradykinesia and tremor. Methods: The research utilised clinical data from 407 PD patients aged 30–100 years at the Central Polyclinic of Durrës, spanning 2011–2022, and included a systematic literature review and statistical analysis comparing physiotherapy outcomes with European Union standards. Results: The research demonstrates the efficiency of physiotherapy in the short and long term in the treatment of PD for patients and medical personnel. All information can be used to increase the functional abilities of patients and minimise complications after physiotherapy and to estimate the effectiveness of different exercises in delaying PD. Older adults, particularly those aged 71–80, are most affected by PD, with males more likely to be diagnosed. Physiotherapy rehabilitation improves motor symptoms, posture, and balance in 30‐80‐year‐olds, but its effectiveness declines with age. Advanced rehabilitation methods in Italy lead to better outcomes, suggesting the potential for improvement in Durres disease. Conclusions: The study emphasises the need for improved rehabilitation strategies for older patients by recommending tailored programs, advanced methods, standardisation, training, and long‐term monitoring. Further research should concentrate on the long‐term sustainability of physiotherapy benefits, the development of targeted interventions for older patients, and the integration of innovative therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background This study aimed to compare colorectal cancer (CRC) awareness between screening-eligible and ineligible individuals in Palestine. Methods Convenience sampling was utilized to recruit Palestinian adults from diverse settings, including hospitals, primary healthcare centers and public spaces across 11 governorates. The evaluation of CRC awareness in terms of signs/symptoms, risk factors and causation myths was conducted using Arabic-translated, modified versions of the validated instruments, the Bowel Cancer Awareness Measure and the Cancer Awareness Measure-Mythical Causes Scale. Results The final analysis included 2698 participants, with 2158 (80.9%) eligible for CRC screening and 540 (19.1%) ineligible for it. The most recognized CRC sign/symptom was 'lump in the abdomen' in both screening-eligible (n = 386, 71.5%) and ineligible (n = 1582, 73.3%) groups. 'Lack of physical activity' was the most recognized risk factor in both groups (eligible: n = 451, 83.5%; ineligible: n = 1766, 81.8%). The most reported causation myth in both groups was 'having a physical trauma' (eligible: n = 340, 63.0%; ineligible: n = 1353, 62.7%). In the screening-eligible group, only 210 participants (38.9%) demonstrated high awareness of CRC signs/symptoms, 213 participants (39.4%) showed high awareness of CRC risk factors and only 46 participants (8.5%) displayed high awareness of CRC causation myths. There were no significant associations between being eligible for screening colonoscopy and the awareness levels of CRC signs/symptoms, risk factors and causation myths. Conclusion Overall, awareness levels of CRC signs/symptoms, risk factors and causation myths were notably low among screening-eligible participants. There were no differences in awareness levels between individuals eligible for colonoscopy and those who were not. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion Unilateral subthalamic nucleus (STN) ablation using magnetic resonance–guided focused ultrasound (MRgFUS) is being explored as a new treatment for asymmetric Parkinson's disease (PD).The aims were to study the efficacy and safety of this treatment in asymmetric PD patients and to characterize the lesions.This prospective, single‐center, open‐label study evaluated asymmetric PD patients at 6 (n = 20) and 12 months (n = 12) after MRgFUS lesion of the STN. The primary outcome was the change in the Movement Disorders Society‐Unified Parkinson's Disease Rating Scale, Part III (MDS‐UPDRS III), score in off medication on the treated side and the adverse events (AEs) at 6‐month follow‐up. We also evaluated cognitive–neuropsychological changes, self‐assessment of clinical improvement, and the correlation of the lesion volume with the motor outcomes.On the treated side, the MDS‐UPDRS III score (mean difference = 13.8) and the scores in rigidity, bradykinesia, and tremor improved (P < 0.001) throughout the follow‐up compared to baseline (at 6 months: rigidity mean difference = 2.8, improvement: 83.5%; bradykinesia mean difference = 6.0, improvement: 69.4%; tremor mean difference = 4.7, improvement: 91.5%). One patient had severe weakness in the treated hemibody, 1 had moderate dyskinesia, and 1 was in moderate confusional state that became mild (weakness) or completely resolved (dyskinesia and confusional state) at 6 months. The rest of the AEs were mild. We observed no clinically relevant changes in cognitive–neuropsychological tests. The percentage of ablation of the STN correlated with the improvement in the total MDS‐UPDRS III and contralateral tremor scores (P < 0.05).Unilateral MRgFUS lesion of the STN resulted in a significant motor improvement. We observed no persistent severe AEs, although mild, mostly transient AEs were frequent. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) has an impact on speech production, manifesting in various ways including alterations in voice quality, challenges in articulating sounds and a decrease in speech rate. Numerous investigations have been conducted to ascertain the oral‐diadochokinesis (O‐DDK) rate in individuals with PD. However, the existing literature lacks exploration of such O‐DDK rates in Malaysia and does not provide consistent evidence regarding the advantage of real‐word repetition. Aims: To explore the effect of gender, stimuli type and PD status and their interactions on the O‐DDK rates among Malaysian‐Malay speakers. Methods & Procedures: O‐DDK performance of 62 participants (29 individuals with PD and 33 healthy elderly) using a non‐word ('pataka'), a Malay real‐word ('patahkan') and an English real‐word ('buttercake') was audio recorded. The number of syllables produced in 8 s was counted. A hierarchical linear modelling was performed to investigate the effects of stimuli type (non‐word, Malay real‐word, English real‐word), PD status (yes, no), gender (male, female) and their interactions on the O‐DDK rate. The model accounted for participants' age as well as the nesting of repeated measurements within participants, thereby providing unbiased estimates of the effects. Outcomes & Results: The stimuli effect was significant (p < 0.0001). Malay real‐word showed the lowest O‐DDK rate (5.03 ± 0.11 syllables/s), followed by English real‐word (5.25 ± 0.11 syllables/s) and non‐word (5.42 ± 0.11 syllables/s). Individuals with PD showed a significantly lower O‐DDK rate compared to healthy elderly (4.73 ± 0.15 syllables/s vs. 5.74 ± 0.14 syllables/s, adjusted p < 0.001). A subsequent analysis indicated that the O‐DDK rate declined in a quadratic pattern. However, neither gender nor age effects were observed. Additionally, no significant two‐way interactions were found between stimuli type, PD status and gender (all p > 0.05). Therefore, the choice of stimuli type has no or only limited effect considering the use of O‐DDK tests in clinical practice for diagnostic purposes. Conclusions & Implications: The observed slowness in O‐DDK among individuals with PD can be attributed to the impact of the movement disorder, specifically bradykinesia, on the physiological aspects of speech production. Speech‐language pathologists can gain insights into the impact of PD on speech production and tailor appropriate intervention strategies to address the specific needs of individuals with PD according to disease stages. WHAT THIS PAPER ADDS: What is already known on this subject: The observed slowness in O‐DDK rates among individuals with PD may stem from the movement disorder's effects on the physiological aspects of speech production, particularly bradykinesia. However, there is a lack of consistent evidence regarding the influence of real‐word repetition and how O‐DDK rates vary across different PD stages. What this study adds to existing knowledge: The O‐DDK rates decline in a quadratic pattern as the PD progresses. The research provides insights into the advantage of real‐word repetition in assessing O‐DDK rates, with Malay real‐word showing the lowest O‐DDK rate, followed by English real‐word and non‐word. What are the potential or actual clinical implications of this work?: Speech‐language pathologists can better understand the evolving nature of speech motor impairments as PD progresses. This insight enables them to design targeted intervention strategies that are sensitive to the specific needs and challenges associated with each PD stage. This finding can guide clinicians in selecting appropriate assessment tools for evaluating speech motor function in PD patients. [ABSTRACT FROM AUTHOR]

Bradykinesia is a term describing several manifestations of movement disruption caused by Parkinson's disease (PD), including movement slowing, amplitude reduction, and gradual decrease of speed and amplitude over multiple repetitions of the same movement. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves bradykinesia in patients with PD. We examined the effect of DBS on specific components of bradykinesia when applied at two locations within the STN, using signal processing techniques to identify the time course of amplitude and frequency of repeated hand pronation-supination movements performed by participants with and without PD. Stimulation at either location increased movement amplitude, increased frequency, and decreased variability, though not to the range observed in the control group. Amplitude and frequency showed decrement within trials, which was similar in PD and control groups and did not change with DBS. Decrement across trials, by contrast, differed between PD and control groups, and was reduced by stimulation. We conclude that DBS improves specific aspects of movement that are disrupted by PD, whereas it does not affect short-term decrement that could reflect muscular fatigue. NEW & NOTEWORTHY: In this study, we examined different components of bradykinesia in patients with Parkinson's disease (PD). We identified different components through signal processing techniques and their response to deep brain stimulation (DBS). We found that some components of bradykinesia respond to stimulation, whereas others do not. This knowledge advances our understanding of brain mechanisms that control movement speed and amplitude. [ABSTRACT FROM AUTHOR]

• More affected (MA) STN comprises more pause-burst neurons compared to less affected. • Oscillations of pause-burst neurons in MA STN correlate with bradykinesia and rigidity. • More affected STNs feature greater oscillation power in the alpha-beta range. We aimed to establish specific biomarkers of Parkinson's disease (PD) by comparing activity of more affected (MA) and less affected (LA) subthalamic nucleus (STN) of patients with prominent clinical asymmetry. We recorded single unit activity and local field potentials (LFP) of the STN during deep brain stimulation surgeries. Neuronal firing patterns and discharge rate, as well as oscillatory features of both single cells and LFP, were analyzed. We observed notable differences in proportions of irregular-burst and pause-burst, but not tonic neurons, between the hemispheres. Oscillations of pause-burst neurons correlated significantly with the bradykinesia and rigidity scores of the corresponding hemibody. LFP derived from MA STN featured greater power in 12–15 Hz. Our results provide evidence that the increased proportion of units with prolonged pauses may be associated with PD. We also speculate that some of them may gain rhythmicity in the alpha-beta range in relation to hypokinetic symptoms, long-term disease, or both. Our findings highlight the relation between specific oscillatory features of the STN, predominance of subthalamic pause-burst units and PD pathophysiology. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder with high prevalence among the elderly, primarily manifested by progressive decline in motor function. The aging global demographic and increased life expectancy have led to a rapid surge in PD cases, imposing a significant societal burden. PD along with other neurodegenerative diseases has garnered increasing attention from the scientific community. In PD, motor symptoms are recognized when approximately 60% of dopaminergic neurons have been damaged. The irreversible feature of PD and benefits of early intervention underscore the importance of disease onset prediction and prompt diagnosis. The advent of digital health technology in recent years has elevated the role of digital biomarkers in precisely and sensitively detecting early PD clinical symptoms, evaluating treatment effectiveness, and guiding clinical medication, focusing especially on motor function, responsiveness and sleep quality assessments. This review examines prevalent digital biomarkers for PD and highlights the latest advancements. [ABSTRACT FROM AUTHOR]

The herbicide atrazine (ATR) has been one of the most widely used herbicides worldwide. However, due to its indiscriminate use, it has been considered an environmental contaminant. Several studies have classified ATR as an endocrine disruptor, and it has been found to have neurotoxic effects on behavior, along with alterations in the dopaminergic, GABAergic, and glutamatergic systems in the basal ganglia of male rodents. These findings suggest that these neurotransmitter systems are targets of this herbicide. However, there are no studies evaluating the neurotoxicity of ATR in female rodents. Our study aimed to assess the effects of repeated IP injections of 100 mg ATR/kg or a vehicle every other day for 2 weeks (six injections) on the locomotor activity, content of monoamines, GABA, glutamate, and glutamine in the striatum, nucleus accumbens, ventral midbrain, and prefrontal cortex, and tyrosine hydroxylase (TH) protein levels in striatum and nucleus accumbens of female rats. Repeated 100 mg ATR/kg injections immediately decreased all the locomotor activity parameters evaluated, and such hypoactivity persisted for at least 48 h after the last ATR administration. The ATR administration increased dopamine and DOPAC content in the nucleus accumbens and the dopamine and DOPAC and serotonin and 5-HIAA content in the ventral midbrain. In contrast, the TH protein levels in the striatum and nucleus accumbens were similar between groups. Meanwhile, GABA, glutamine, and glutamate levels remained unaltered in all brain regions evaluated. The observed behavioral alterations could be associated with the monoamine changes presented by the rats. These data reveal that the nucleus accumbens and ventral midbrain are susceptible to repeated ATR exposure in female rats. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Invasive deep brain stimulation (DBS) has been shown to be effective in treating patients with Parkinson's disease (PD), yet its clinical use is limited to patients at the advanced stage of the disease. Transcranial temporal interference stimulation (tTIS) may be a novel nonneurosurgical and safer alternative, yet its therapeutic potential remains unexplored.This pilot study aims to examine the feasibility and safety of tTIS targeting the right globus pallidus internus (GPi) for motor symptoms in patients with PD.Twelve participants with mild PD completed this randomized, double‐blind, and sham‐controlled experiment. Each of them received either 20‐minute or sham tTIS of the right GPi. Before and immediately after the stimulation, participants completed the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS‐III) in the “medication‐on” state to assess the motor symptoms. The blinding efficacy and side effects were also assessed.tTIS was well tolerated by participants, with only mild, transient adverse effects reported. tTIS significantly reduced MDS‐UPDRS‐III scores by 6.64 points (14.7%), particularly in bradykinesia (23.5%) and tremor (15.3%). The left side showed more significant alleviation in motor symptoms, particularly bradykinesia, compared to the right side. Participants with severer bradykinesia and tremor before stimulation experienced greater improvement after tTIS.This pilot study suggests that the tTIS, as a novel noninvasive DBS approach, is feasible and safe for alleviating motor symptoms in mild PD, especially bradykinesia and tremor. Future larger‐scale and more definitive studies are needed to confirm the benefits. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: The mechanism of myocardial damage in dengue could be the release of inflammatory mediators or the direct action of the dengue virus on myocytes leading to myocarditis. The release of inflammatory mediators is more in a severe form of the disease that correlates to the higher incidence of cardiac manifestations in patients with severe dengue. Aim: To estimate the proportion of cardiac involvement among patients with dengue fever admitted in Kanachur Medical College, Mangaluru based on clinical, serological, electrocardiographical and echocardiographical evaluation. Materials and Methods: A hospital based cross sectional study was conducted at Kanachur Medical College, Mangaluru during duration of 1 year (March, 2022-March, 2023). 185 patients were recruited in this study. A detailed history and clinical examination was recorded on structured proforma. Hematological and biochemical investigations were done at the time of admission. Study variables included Systemic hypertension, Dyslipidemia, symptoms of cardiac involvement such as palpitations and chest discomfort. Results: Out of 185 patients, 14.6% were less than 30 years, 20.5% were 31-40 years old, 30.8% were 41-50 years old, 22.2% were 51-60 years old, and 11.9% were >60 years old. 51% patients were females and 49% were males. According to distribution of cardiac symptoms, 72.9% were normal, 11.9% had bradycardia, 4.3% had tachycardia, 4.3% had ischaemic type chest pain, 3.8% had palpitations, and 2.7% had dyspnoea. 76.2% patients had normal ECG findings, 10.8% had sinus bradycardia, 6.7% had sinus tachycardia, 1.7% had heart block, 1.4% had dynamic ST-T, and 0.6% had atrial fibrillation. 87.5% patients had normal ECHO findings, 9.1% had wall motion abnormalities, 2.2% had LV systolic dysfunction, and 1.1% had Valvular regurgitant lesion. Conclusion: From present study, we can say that the most accurate test for detecting myocarditis is ECG. The most frequent ECG abnormality was sinus bradycardia. The most common ECHO abnormality was wall motion abnormalities with global hypokinesia. [ABSTRACT FROM AUTHOR]

Amplitude-based exercise training has been shown to be effective in the motor performance of individuals with idiopathic Parkinson's disease, with limited research investigating its effects on Parkinson plus syndromes such as olivopontocerebellar atrophy (OPCA). The purpose of this clinical case report is to examine the effects of amplitude-based training exercises on an individual with OPCA. A 68-year-old man with a 14-month history of OPCA presented to physical therapy with bradykinesia, rigidity, and postural instability. The individual participated in 34 intervention sessions. Pre- and post-test measurements were collected for the following outcome measures: Five Times Sit to Stand (FTSTS); Functional Gait Assessment (FGA); Activities-Specific Balance Confidence Scale (ABC-6); 9 Hole Peg Test (9HPT); preferred and maximal gait speed. Improvements reaching Minimum Detectable Change (MDC) or Minimal Clinically Important Difference (MCID) were recorded with a pre (Week 1) and post (Week 20) intervention: FGA score (4-point improvement (MDC95 = 4 points), preferred gait speed (0.09 meters/second improvement (MCID = 0.05 meters/second)), FTSTS (6-second improvement (MDC95 = 2.3 seconds)), and 9HPT on the dominant hand (3-second improvement (MDC95 = 2.6 seconds)). Fluctuations during the plan of care were observed for these measures, and additional outcomes did not demonstrate a worsening of function. In an individual with OPCA, amplitude-based exercise training as a component of the plan of care increased dynamic balance in walking, gait speed, and hand dexterity. However, these results need to be validated on a larger sample of individuals with OPCA through randomized controlled trials. [ABSTRACT FROM AUTHOR]

Objective: Bradykinesia and rigidity are considered closely related motor signs in Parkinson disease (PD), but recent neurophysiological findings suggest distinct pathophysiological mechanisms. This study aims to examine and compare longitudinal changes in bradykinesia and rigidity in PD patients treated with bilateral subthalamic nucleus deep brain stimulation (STN‐DBS). Methods: In this retrospective cohort study, the clinical progression of appendicular and axial bradykinesia and rigidity was assessed up to 15 years after STN‐DBS in the best treatment conditions (ON medication and ON stimulation). The severity of bradykinesia and rigidity was examined using ad hoc composite scores from specific subitems of the Unified Parkinson's Disease Rating Scale motor part (UPDRS‐III). Short‐ and long‐term predictors of bradykinesia and rigidity were analyzed through linear regression analysis, considering various preoperative demographic and clinical data, including disease duration and severity, phenotype, motor and cognitive scores (eg, frontal score), and medication. Results: A total of 301 patients were examined before and 1 year after surgery. Among them, 101 and 56 individuals were also evaluated at 10‐year and 15‐year follow‐ups, respectively. Bradykinesia significantly worsened after surgery, especially in appendicular segments (p < 0.001). Conversely, rigidity showed sustained benefit, with unchanged clinical scores compared to preoperative assessment (p > 0.05). Preoperative motor disability (eg, composite scores from the UPDRS‐III) predicted short‐ and long‐term outcomes for both bradykinesia and rigidity (p < 0.01). Executive dysfunction was specifically linked to bradykinesia but not to rigidity (p < 0.05). Interpretation: Bradykinesia and rigidity show long‐term divergent progression in PD following STN‐DBS and are associated with independent clinical factors, supporting the hypothesis of partially distinct pathophysiology. ANN NEUROL 2024;96:234–246 [ABSTRACT FROM AUTHOR]

Background: Subtle parkinsonian signs, i.e., rest tremor and bradykinesia, are considered soft signs for defining essential tremor (ET) plus. Objectives: Our study aimed to further characterize subtle parkinsonian signs in a relatively large sample of ET patients from a clinical and neurophysiological perspective. Methods: We employed clinical scales and kinematic techniques to assess a sample of 82 ET patients. Eighty healthy controls matched for gender and age were also included. The primary focus of our study was to conduct a comparative analysis of ET patients (without any soft signs) and ET-plus patients with rest tremor and/or bradykinesia. Additionally, we investigated the asymmetry and side concordance of these soft signs. Results: In ET-plus patients with parkinsonian soft signs (56.10% of the sample), rest tremor was clinically observed in 41.30% of cases, bradykinesia in 30.43%, and rest tremor plus bradykinesia in 28.26%. Patients with rest tremor had more severe and widespread action tremor than other patients. Furthermore, we observed a positive correlation between the amplitude of action and rest tremor. Most ET-plus patients had an asymmetry of rest tremor and bradykinesia. There was no side concordance between these soft signs, as confirmed through both clinical examination and kinematic evaluation. Conclusions: Rest tremor and bradykinesia are frequently observed in ET and are often asymmetric but not concordant. Our findings provide a better insight into the phenomenology of ET and suggest that the parkinsonian soft signs (rest tremor and bradykinesia) in ET-plus may originate from distinct pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis was conducted to evaluate potential differences in symptoms between PD patients with or without RBD. Methods: A systematic search was conducted in PubMed, Cochrane, Embase, and Web of Science databases (as of August 16, 2023), to identify relevant studies on PD and RBD. Statistical analysis was performed using Stata 15.0. Continuous variables were analyzed using the standardized mean difference (SMD) and 95% confidence interval (95% CI), while count data were assessed using the odds ratio (OR) and 95% CI as statistical effect sizes. Heterogeneity among all included studies was tested; for studies with low heterogeneity (I² < 50%), a fixed-effects model was used to calculate statistical results. For studies with relatively high heterogeneity (I² > 50%), a random-effects model was applied, followed by sensitivity and subgroup analyses to identify sources of heterogeneity. Results: A total of 5,672 subjects were involved in this study. Compared to the NRBD group, the UPDRS-III score in the RBD group was significantly higher (SMD = 0.20, 95% CI: [0.11, 0.29], P < 0.001), and the Hoehn-Yahr score in the RBD group was also significantly higher (SMD = 0.29, 95% CI: [0.03, 0.55], P < 0.001). Patients with PD in the RBD group had more severe cognitive impairments than those in the NRBD group (SMD = -0.30, 95% CI: [-0.48, -0.11], P < 0.001). The incidence of hallucination in PD patients in the RBD group was 3.0 times that of the NRBD group (OR = 3.0, 95% CI: [2.15, 4.20], P = 0.110). PD patients in the RBD group also experienced more severe anxiety symptoms (SMD = 0.13, 95% CI: [-0.26, 0.51], P < 0.001), had higher scores in depression scales (SMD = 0.22, 95% CI: [0.02, 0.43], P < 0.001), and higher scores in sleep disorder scales than those in NRBD group (SMD = 0.10, 95% CI: [-0.11, 0.31], P < 0.001). Conclusion: Results show PD patients with co-occurring RBD have more severe motor and non-motor symptoms likely due to overlapping affected regions in RBD and PD-related pathology, plus broader neurodegeneration seen in PD patients with RBD. [ABSTRACT FROM AUTHOR]

Reduced spontaneous blinking is a recognized Parkinson's disease (PD) feature. In contrast, voluntary blinking has been less studied and might serve as a measurable marker of facial bradykinesia. We tested 31 PD patients and 31 controls. Participants were filmed during conversation and a rapid blinking task. Both tasks were videorecorded to count the number of blinks per second. PD patients had lower blink rates. Rapid blinking accurately discriminated between groups with 77% sensitivity and 71% specificity. To conclude, rapid blinking may be a simple and quantifiable task of facial bradykinesia. Plain Language Summary: Decreased blinking without conscious effort is a well-known characteristic of Parkinson's disease (PD). However, voluntary blinking, which is blinking on purpose, has not been studied as much and could be a sign of slower facial movements. We studied a group of people with PD and another one without the disease. We recorded videos of them talking and doing a task where they blinked quickly. Then, we counted how many times they blinked per second in each video. We found that people with PD blinked less often. The rapid blinking task accurately distinguished between those with PD and those without it, being correct about 77% of the time for spotting PD and 71% for spotting non-PD. In conclusion, the rapid blinking task could be a simple and measurable way to identify slower facial movements in PD. [ABSTRACT FROM AUTHOR]

Introduction: The current approach to assessing bradykinesia in Parkinson's Disease relies on the Unified Parkinson's Disease Rating Scale (UPDRS), which is a numeric scale. Inertial sensors offer the ability to probe subcomponents of bradykinesia: motor speed, amplitude, and rhythm. Thus, we sought to investigate the differential effects of high-frequency compared to low-frequency subthalamic nucleus (STN) deep brain stimulation (DBS) on these quantified facets of bradykinesia. Methods: We recruited advanced Parkinson's Disease subjects with a chronic bilateral subthalamic nucleus (STN) DBS implantation to a single-blind stimulation trial where each combination of medication state (OFF/ON), electrode contacts, and stimulation frequency (60 Hz/180 Hz) was assessed. The Kinesia One sensor system was used to measure upper limb bradykinesia. For each stimulation trial, subjects performed extremity motor tasks. Sensor data were recorded continuously. We identified STN DBS parameters that were associated with improved upper extremity bradykinesia symptoms using a mixed linear regression model. Results: We recruited 22 subjects (6 females) for this study. The 180 Hz STN DBS (compared to the 60 Hz STN DBS) and dopaminergic medications improved all subcomponents of upper extremity bradykinesia (motor speed, amplitude, and rhythm). For the motor rhythm subcomponent of bradykinesia, ventral contacts yielded improved symptom improvement compared to dorsal contacts. Conclusion: The differential impact of high- and low-frequency STN DBS on the symptoms of bradykinesia may advise programming for these patients but warrants further investigation. Wearable sensors represent a valuable addition to the armamentarium that furthers our ability to conduct objective, quantitative clinical assessments. [ABSTRACT FROM AUTHOR]

In addition to the cardinal motor symptoms, pain is a major non-motor symptom of Parkinson's disease (PD). Neuroinflammation in the substantia nigra pars compacta and dorsal striatum is involved in neurodegeneration in PD. But the polarization of microglia and astrocytes in the dorsal striatum and their contribution to motor deficits and hyperalgesia in PD have not been characterized. In the present study, we observed that hemiparkinsonian mice established by unilateral 6-OHDA injection in the medial forebrain bundle exhibited motor deficits and mechanical allodynia. In these mice, both microglia and astrocytes in the dorsal striatum were activated and polarized to M1/M2 microglia and A1/A2 astrocytes as genes specific to these cells were upregulated. These effects peaked 7 days after 6-OHDA injection. Meanwhile, striatal astrocytes in parkinsonian mice also displayed hyperpolarized membrane potentials, enhanced voltage-gated potassium currents, and dysfunction in inwardly rectifying potassium channels and glutamate transporters. Systemic administration of minocycline, a microglia inhibitor, attenuated the expression of genes specific to M1 microglia and A1 astrocytes in the dorsal striatum (but not those specific to M2 microglia and A2 astrocytes), attenuated the damage in the nigrostriatal dopaminergic system, and alleviated the motor deficits and mechanical allodynia in parkinsonian mice. By contrast, local administration of minocycline into the dorsal striatum of parkinsonian mice mitigated only hyperalgesia. This study suggests that M1 microglia and A1 astrocytes in the dorsal striatum may play important roles in the development of pathophysiology underlying hyperalgesia in the early stages of PD. [ABSTRACT FROM AUTHOR]

Reverse takotsubo cardiomyopathy (rTTC), also known as inverted takotsubo syndrome, is an acute cardiac syndrome that mimics myocardial infarction and accounts for a smaller proportion of cases compared to the classic takotsubo syndrome. While the exact prevalence is not well-established, studies suggest that the proportion of patients with the rTTC variant out of all Takotsubo Cardiomyopathy (TTC) according to different literature ranges from 1-23%. This variant of TTC is characterized by basal and/or mid-akinesis/hypokinesis associated with apical hyperkinesis that resolves spontaneously. We report a case of a 30-year-old male patient who presented with complaints of sudden crushing chest pain and shortness of breath. After conducting a thorough examination, the patient’s diagnostic workup confirmed reverse takotsubo cardiomyopathy, elucidating the underlying cardiac pathology

Introduction: Bradykinesia is an essential diagnostic criterion for Parkinson's disease (PD) but is frequently observed in many non-parkinsonian movement disorders, complicating differential diagnosis, particularly in disorders featuring tremors. The presence of bradykinetic features in the subset of dystonic tremors (DT), either "pure" dystonic tremors or tremors associated with dystonia, remains currently unexplored. The aim of the current study was to evaluate upper limb bradykinesia in DT patients, comparing them with healthy controls (HC) and patients with PD by observing repetitive finger tapping (FT). Methods: The protocol consisted of two main parts. Initially, the kinematic recording of repetitive FT was performed using optical hand tracking system (Leap Motion Controller). The values of amplitude, amplitude decrement, frequency, frequency decrement, speed, acceleration and number of halts of FT were calculated. Subsequently, three independent movement disorder specialists from different movement disorders centres, blinded to the diagnosis, rated the presence of FT bradykinesia based on video recordings. Results: Thirty-six subjects participated in the study (12 DT, 12 HC and 12 earlystage PD). Kinematic analysis revealed no significant difference in the selected parameters of FT bradykinesia between DT patients and HC. In comparisons between DT and PD patients, PD patients exhibited bigger amplitude decrement and slower FT performance. In the blinded clinical assessment, bradykinesia was rated, on average, as being present in 41.6% of DT patients, 27.7% of HC, and 91.7% of PD patients. While overall inter-rater agreement was moderate, weak agreement was noted within the DT group. Discussion: Clinical ratings indicated signs of bradykinesia in almost half of DT patients. The objective kinematic analysis confirmed comparable parameters between DT and HC individuals, with more pronounced abnormalities in PD across various kinematic parameters. Interpretation of bradykinesia signs in tremor patients with DT should be approached cautiously and objective motion analysis might complement the diagnostic process and serve as a decision support system in the choice of clinical entities. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions, and its impact extends beyond physical abnormalities into emotional well-being and cognitive symptoms. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) leads to an array of dysfunctions in the functioning of the basal ganglia (BG) circuitry that manifests into PD. While active research is being carried out to find the root cause of SNc cell death, various therapeutic techniques are used to manage the symptoms of PD. The most common approach in managing the symptoms is replenishing the lost dopamine in the form of taking dopaminergic medications such as levodopa, despite its long-term complications. Another commonly used intervention for PD is deep brain stimulation (DBS). DBS is most commonly used when levodopa medication efficacy is reduced, and, in combination with levodopa medication, it helps reduce the required dosage of medication, prolonging the therapeutic effect. DBS is also a first choice option when motor complications such as dyskinesia emerge as a side effect of medication. Several studies have also reported that though DBS is found to be effective in suppressing severe motor symptoms such as tremors and rigidity, it has an adverse effect on cognitive capabilities. Henceforth, it is important to understand the exact mechanism of DBS in alleviating motor symptoms. A computational model of DBS stimulation for motor symptoms will offer great insights into understanding the mechanisms underlying DBS, and, along this line, in our current study, we modeled a cortico-basal ganglia circuitry of arm reaching, where we simulated healthy control (HC) and PD symptoms as well as the DBS effect on PD tremor and bradykinesia. Our modeling results reveal that PD tremors are more correlated with the theta band, while bradykinesia is more correlated with the beta band of the frequency spectrum of the local field potential (LFP) of the subthalamic nucleus (STN) neurons. With a DBS current of 220 pA, 130 Hz, and a 100 microsecond pulse-width, we could found the maximum therapeutic effect for the pathological dynamics simulated using our model using a set of parameter values. However, the exact DBS characteristics vary from patient to patient, and this can be further studied by exploring the model parameter space. This model can be extended to study different DBS targets and accommodate cognitive dynamics in the future to study the impact of DBS on cognitive symptoms and thereby optimize the parameters to produce optimal performance effects across modalities. Combining DBS with rehabilitation is another frontier where DBS can reduce symptoms such as tremors and rigidity, enabling patients to participate in their therapy. With DBS providing instant relief to patients, a combination of DBS and rehabilitation can enhance neural plasticity. One of the key motivations behind combining DBS with rehabilitation is to expect comparable results in motor performance even with milder DBS currents. [ABSTRACT FROM AUTHOR]

A 29-year-old female, born to consanguineous parents, was found with unmeasurable levels of vitamin D (<10 nmol/L) after routine biochemical screening during her first pregnancy. She did not respond to either oral or intramuscular vitamin D supplementation and was an otherwise healthy young woman, with no signs of rickets, osteomalacia, osteoporosis, or secondary hyperparathyroidism. Western blot analysis revealed total lack of vitamin D binding protein, and next generation sequencing confirmed a novel, pathogenic homozygote loss-of-function mutation in exon 13 of the group-specific component gene , that encodes the poly A tail for vitamin D binding protein. She was therefore diagnosed with hereditary DBP deficiency, and vitamin D supplementation was diminished to life-long regular vitamin D supplementation (25 μg per day). This case is extremely interesting, as it expands our knowledge of vitamin D physiology and supports the free hormone hypothesis, given that the patient was asymptomatic despite no measurable levels of vitamin D. [ABSTRACT FROM AUTHOR]

We performed a comprehensive study of protein (total protein, medium-molecular-weight peptides, creatinine, and urea), purine (uric acid), and lipid (cholesterol, triglycerides) metabolism, activity of AST, ALT, and acid phosphatase in blood plasma of white male rats under conditions of restriction of motor activity up to 28 days. Patterns of changes in metabolic profile during hypokinesia were established: prevalence of catabolic processes and atherogenic shifts in the lipid spectrum with maximum manifestation on 14-21 days of the experiment. [ABSTRACT FROM AUTHOR]

Introduction: Lower urinary tract symptoms (LUTSs) are a diverse array of urinary and pelvic dysfunctions that can emerge from childhood, extend through adulthood, and persist into older age. This narrative review aims to provide a comprehensive perspective on the continuum of LUTS and shed light on the underlying mechanisms and clinical implications that span across the lower urinary tract. Methods: A panel of five experts from Belgium, the Netherlands, India, Denmark, and the United States participated in an intensive research to explore and pinpoint existing insights into the lifelong concept of LUTS, particularly at the pelvic level. The experts reviewed the existing literature and held a webinar to discuss their findings. Results: Childhood LUTS can persist, resolve, or progress into bladder underactivity, dysfunctional voiding, or pain syndromes. The Lifelong character can be explained by pelvic organ cross‐talk facilitated through complex neurological and nonneurological interactions. At the molecular level, the role of vasopressin receptors in the bladder's modulation and their potential relevance to therapeutic strategies for LUTS are explored. Frailty emerges as a parallel concept to lifelong LUTS, with a complex and synergistic relationship. Frailty, not solely an age‐related condition, accentuates LUTS severity with insufficient evidence regarding the effectiveness and safety profile of the available therapeutic modalities. Conclusion: Understanding lifelong LUTSs offers insights into genetic, anatomical, neurological, and molecular mechanisms. Further research could identify predictive biomarkers, elucidate the role of clinically translatable elements in pelvic cross‐talk, and uncover molecular signatures for personalized management. [ABSTRACT FROM AUTHOR]

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Diarrhea is a common gastrointestinal disorder in horses, with diet-induced diarrhea being an emerging challenge. This study aimed to investigate the gut microbiota differences in healthy and diet-induced diarrheic horses and evaluate the effectiveness of fecal microbiota transplantation (FMT) and carbonate buffer mixture (CBM) as potential therapeutic approaches. Twenty healthy horses were included in the study, with four groups: Control, Diarrhea, CBM, and FMT. Diarrhea was induced using oligofructose, and fecal samples were collected for microbiota analysis. FMT and CBM treatments were administered orally using donor fecal matter, and formula mixture, respectively. Clinical parameters, serum levels, intestinal tissue histopathology, and fecal microbiota profiles were evaluated. The results showed that diarrhea induction disbalanced the gut microbiota with decreased diversity and richness, affected clinical parameters including elevated body temperature and diarrhea score, and decreased fecal pH, increased inflammatory responses such as increased serum LPS, IL-17A, lactic acid and total protein, and caused damage in the colon tissue. CBM and FMT treatments altered the gut microbiota composition, restoring it towards a healthier profile compared to diarrheic, restored the gut microbiota composition to healthier states, improved clinical symptoms including decreased body temperature and diarrhea score, and increased fecal pH, decreased inflammatory responses such as increased serum LPS, IL- 17A, lactic acid and total protein, and repaired tissue damage. CBM and FMT Spearman correlation analysis identified specific bacterial taxa associated with host parameters and inflammation. FMT and CBM treatments showed promising therapeutic effects in managing oligofructose-induced diarrhea in horses. The findings provide valuable insights into the management and treatment of diarrhea in horses and suggest the potential of combined CBM and FMT approaches for optimal therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Prolonged bed rest can have a significant negative effect on skeletal muscles, leading to muscle wasting and reduced strength. This process can take as little as 10 days in healthy individuals, with the loss of muscle mass and strength being particularly pronounced during the first week of immobilization. Head-down tilt bed rest (HDTBR) is a method used to simulate physiological changes that occur in weightlessness during spaceflight. This technique involves lying in bed with the head tilted downward. Here, we analyze the key anabolic markers of the human m. soleus during 21 days of HDTBR. Six healthy male volunteers, aged 25–35 years, were exposed to 21 days of strict bed rest at a tilt angle of –6°. A needle biopsy of the m. soleus was performed via the Bergström method before the onset of HDTBR and on day 21 after that. The biopsy material was immediately frozen in liquid nitrogen for further Western blot and PCR analysis. A study of mTORC1 substrates showed a significant decrease in p70 and 4EBP1 phosphorylation after HDTBR. We also observed a significant decrease in the phosphorylation of another ribosomal kinase, p90RSK, a significant increase in eEF2 phosphorylation, and an increase in eEF2k mRNA expression. In addition, the phosphorylation of AMPK and its substrate ACC decreased after HDTBR. The data obtained in this work support the hypothesis that a decrease in protein synthesis, together with an increase in proteolysis, contributes to the development of human m. soleus atrophy after 21 days of HDTBR. [ABSTRACT FROM AUTHOR]

Background More than half of childhood tuberculosis cases remain undiagnosed yearly. The World Health Organization recommends the Xpert-Ultra assay as a first pediatric diagnosis test, but microbiological confirmation remains low. We aimed to determine the diagnostic performance of Xpert-Ultra with stool and urine samples in presumptive pediatric tuberculosis cases in 2 high-tuberculosis-burden settings. Methods This Médecins Sans Frontières cross-sectional multicentric study took place at Simão Mendes Hospital, Guinea-Bissau (July 2019 to April 2020) and in Malakal Hospital, South Sudan (April 2021 to June 2023). Children aged 6 months to 15 years with presumptive tuberculosis underwent clinical and laboratory assessment, with 1 respiratory and/or extrapulmonary sample (reference standard [RS]), 1 stool, and 1 urine specimen analyzed with Xpert-Ultra. Results A total of 563 children were enrolled in the study, 133 from Bissau and 400 from Malakal; 30 were excluded. Confirmation of tuberculosis was achieved in 75 (14.1%), while 248 (46.5%) had unconfirmed tuberculosis. Of 553 with an RS specimen, the overall diagnostic yield was 12.4% (66 of 533). A total of 493 stool and 524 urine samples were used to evaluate the performance of Xpert-Ultra with these samples. Compared with the RS, the sensitivity and specificity of Xpert-Ultra were 62.5% (95% confidence interval, 49.4%–74%) and 98.3% (96.7%–99.2%), respectively, with stool samples, and 13.9% (7.5%–24.3%) and 99.4% (98.1%–99.8%) with urine samples. Nine patients were positive with stool and/or urine samples but negative with the RS. Conclusions Xpert-Ultra in stool samples showed moderate to high sensitivity and high specificity compared with the RS and an added diagnostic yield when RS results were negative. Xpert-Ultra in stool samples was useful in extrapulmonary cases. Xpert-Ultra in urine samples showed low test performance. Clinical Trials Registration NCT06239337 [ABSTRACT FROM AUTHOR]

Background: 'PD Warrior' (PDW) is a popular exercise programme for Parkinson disease; however, there are no published studies on the outcomes of the programme. Aims: To investigate short‐term functional and quality of life (QoL) outcomes after the PDW 10‐week programme in a pilot study of individuals with early Parkinson Disease (PD). Methods: Twenty individuals with PD (Hoehn & Yahr 1–3) attending a hospital outpatient clinic were recruited into the PDW 10‐week programme, comprising a weekly 1‐h supervised class complemented by an individualised daily home exercise programme. Participants had the following assessments at baseline and after completion of the programme: Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS‐UPDRS) Part III, timed up‐and‐go (TUG), 10‐m walk test (10mWT), 6‐min walking test (6MWT), balance tests, fine motor skills, 7‐day Parkinson KinetiGraph (PKG) and PDQ‐39 QoL scale. Results: Seventeen individuals completed the programme. Significant improvements were observed in MDS‐UPDRS motor score (P = 0.019, d = 0.68, MCID 7); 6MWT distance (P < 0.001, d = 1.16); walking time during motor or cognitive dual tasking (P = 0.006, d = 0.77; P = 0.005, d = 0.79, respectively); and the PDQ‐39 emotional well‐being subdomain (P = 0.009; MCID 4.2); as well as improvements trending to significance in bradykinesia (P = 0.025, d = 0.73), 10mWT walking time (P = 0.023, d = 0.61) and borderline improvement in balance (P = 0.056, d = 0.50). Conclusions: The outcomes of this study support the efficacy of the PDW programme in individuals with early PD and provide justification for future trials and investigation of its effects. [ABSTRACT FROM AUTHOR]

Introduction: The definitive diagnosis of coronavirus disease-2019 (COVID-19) infection is made by polymerase chain reaction (PCR) tests on nasopharyngeal and oropharyngeal swab samples. However, the presence of viral RNA has also been identified in stool samples. In this study, we aimed to investigate the relationship between severe acute respiratory syndrome-coronavirus-2 positivity in stool and the outcomes of COVID-19 disease. Methods: Fifty-four patients who were hospitalized between April-June 2020 and had positive COVID-19 PCR tests in nasopharyngeal and oropharyngeal swab samples were included in the study. PCR was performed on the stool samples of all patients. In addition, laboratory findings, clinical data, and computed tomography (CT) results of these patients were recorded and analyzed. Results: Among the patients, 13 out of 28 (46.4%) with positive fecal PCR test results were female, whereas 11 out of 26 (46.4%) with negative fecal PCR test results were female. Furthermore, 19 out of 28 patients (67.9%) with positive fecal PCR test results recovered, whereas 23 out of 26 patients (88.5%) with negative fecal PCR test results recovered. Notably, patients with fecal PCR-positive results exhibited more severe dyspnea, higher blood pressure, abnormal CT findings, and elevated D-dimer levels. Moreover, compared with patients with negative PCR results, those with positive fecal PCR results had lower levels of procalcitonin, hemoglobin, hematocrit, and lymphocytes. Conclusion: Considering the relationship between stool PCR positivity and the prognosis of the disease and laboratory test results, routine stool PCR tests may be useful, especially in COVID-19 patients presenting with gastrointestinal symptoms. [ABSTRACT FROM AUTHOR]

Objectives Purpose in life has been associated with diverse health outcomes; however, few studies have examined its associations with progressive motor decline in older adults. We tested if higher purpose would be associated with lower likelihood of incident parkinsonism as well as with lower levels and slower rates of increase in parkinsonian signs. Methods Participants were 2,626 older adults from the Rush Memory and Aging Project and Minority Aging Research Study followed for an average of 7.2 years (standard deviation [ SD ] = 4.6). Purpose was measured using the purpose in life subscale of the modified Ryff's and Keyes's measure of psychological well-being. Four parkinsonian signs (i.e. parkinsonian gait, rigidity, bradykinesia, and tremor) were assessed using the United Parkinson's Disease Rating Scale. We examined purpose with risk of developing incident parkinsonism using Cox proportional hazards models. We also used linear mixed-effect models to assess the association between purpose and parkinsonian sign trajectories. Results After including demographics, health conditions, and health behaviors in the model, for a 1- SD increase in purpose, the hazards ratio for incident parkinsonism was 0.88 (95% confidence interval [CI] 0.80, 0.97). A 1- SD increase in purpose was associated with a −0.19 (95% CI −0.24, −0.15) point lower score in the global parkinsonian summary score at baseline but no differences in rate of change were evident. Discussion Higher purpose was associated with lower hazards of incident parkinsonism and lower levels of parkinsonian signs at baseline. Associations were seen even after adjustment for a wide range of covariates. Findings suggest higher purpose may contribute to maintenance of healthy physical function among older adults. [ABSTRACT FROM AUTHOR]

The SARS‐CoV‐2 VIrus PERsistence (VIPER) study investigated the presence of long‐lasting SARS‐CoV‐2 RNA in plasma, stool, urine, and nasopharyngeal samples in COVID‐19 survivors. The presence of SARS‐CoV‐2 RNA reverse transcription polymerase chain reactions (RT‐PCR) were analyzed within plasma, stool, urine, and nasopharyngeal swab samples in COVID‐19 survivors with post‐COVID symptoms and a comparison group of COVID‐19 survivors without post‐COVID symptoms matched by age, sex, body mass index and vaccination status. Participants self‐reported the presence of any post‐COVID symptom (defined as a symptom that started no later than 3 months after the initial infection). Fifty‐seven (57.9% women, age: 51.1, standard deviation [SD]: 10.4 years) previously hospitalized COVID‐19 survivors with post‐COVID symptoms and 55 (56.4% women, age: 50.0, SD: 12.8 years) matched individuals who had a past SARS‐CoV‐2 infection without post‐COVID symptoms were evaluated 27 (SD 7.5) and 26 (SD 8.7) months after hospital discharge, respectively. The presence of SARS‐CoV‐2 RNA was identified in three nasopharyngeal samples of patients with post‐COVID symptoms (5.2%) but not in plasma, stool, or urine samples. Thus, SARS‐CoV‐2 RNA was not identified in any sample of survivors without post‐COVID symptoms. The most prevalent post‐COVID symptoms consisted of fatigue (93%), dyspnea, and pain (both, 87.7%). This study did not find SARS‐CoV‐2 RNA in plasma, stool, or urine samples, 2 years after the infection. A prevalence of 5.2% of SARS‐CoV‐2 RNA in nasopharyngeal samples, suggesting a potential active or recent reinfection, was found in patients with post‐COVID symptoms. These results do not support the association between SARS‐CoV‐2 RNA in plasma, stool, urine, or nasopharyngeal swab samples and post‐COVID symptomatology in the recruited population. [ABSTRACT FROM AUTHOR]

Overweight and obesity are one of the most serious social and medical problems today. It is appropriate to single out a special category of young women aged 18–35 years with excessive body weight, that is, the age which is capable of ensuring the reproductive potential of the future. The objective: to determine the probable factors of metabolic imbalance and the main parameters of reproductive health disorders in young overweight women. Materials and methods. Reproductive health parameters and the main predictors of its impairment were evaluated in two groups of patients – the main group (890 women with BMI > 25.0 kg/m² ) and a control group (40 patients with BMI of 18.5–24.9 kg/m² ). The main group was divided into two subgroups taking into account the age of formation of overweight and obesity: I subgroup – 596 women with pubertal obesity (66.9%) and II subgroup – 294 women with overweight in the postpubertal period (33.1%). Results. A high rate of pregnancy complications (86.9%), gestational diabetes (25.8%), preeclampsia (34.1%), premature birth and low birth weight fetus (20.9%), as well as the birth of a girl with a large body weight (24.4%), can become modified factors in the formation of the reproductive system according to the characteristics of the “perinatal portrait” and form the basis of screening programs. The relationship between the early introduction of complementary foods and the absence of breastfeeding and the presence of obesity in the girl in the future was established (OR=7.25; 95% CI: 2.99–17.59; χ² =23.53, p<0.0001). Attention should be paid to reproductive function disorders: amenorrhea was found 1.7 times more often in the case of postpubertal obesity, as well as abnormal uterine bleeding or metrorrhagia, infertility (24.4%), dyshormonal breast diseases (34.7%), polycystic ovary syndrome (59.8%), proliferative processes of the endometrium and myometrium (34.7%), as well as the formation of endometrial hyperplasia and polyposis with age (25.8%). A high percentage of stressogenic factors was determined in the examined cohort of patients, which could initiate the manifestation of metabolic and endocrine disorders in 569 cases – 63.9% (OR=4.14; 95% CI: 2.07–8.25; χ² =17.38, p<0.0001). Conclusions. Probable predictors of impaired fat metabolism in young women were statistically identified: heredity from the mothers of such patients regarding metabolic and endocrine disorders, body weight at birth more than 4000 g and artificial feeding, early age of menarche, pubertal paratrophy, stress factors, infectious diseases during menarche, hypodynamia and a high level of intellectual differentiation. The reproductive health of women with overweight and obesity is characterized by a high frequency of menstrual cycle disorders, increased manifestations of changes in the vaginal microbiome and dysuric symptoms, as well as infertility, hormonedependent diseases, and impaired reproductive function. [ABSTRACT FROM AUTHOR]

Acute intermittent porphyria is caused due to deficiency of porphobilinogen deaminase and usually presents with classic triad of neurologic dysfunction, abdominal pain and psychiatric disturbances. A 16-year old unmarried girl presented with 1-day history of recurrent episodes of generalized tonic clonic fits. There was history of mild diffuse abdominal pain for 15 days partially relieved by taking drotaverine. On examination, she was vitally stable and afebrile. Once the fits had stopped, there was no focal motor, sensory or cerebellar neurologic deficit and negative signs of neck rigidity. Initial investigations revealed microcytic anemia and a low normal sodium. Her ESR, CRP, CSF analysis, MRI scan (brain), EEG and aerobic cultures were normal. Urine had a pinkish red color and her 24-hour urine porphobilinogen were raised at 23 mg/24 h (normal range 0-3.4 mg/24 h) with normal fecal porphyrin levels. A diagnosis of Acute Intermittent Porphyria (AIP) was made and 10% dextrose infusion was stared which resulted in recovery. Her attack was most likely precipitated by drotaverine and it was withdrawn. Counseling and education about her diagnosis and possible triggering factors was done. She was asymptomatic at discharge and remained stable on follow-up at 4 weeks. [ABSTRACT FROM AUTHOR]

Introduction: Although restriction of vertical ocular range of motion is known to be the hallmark of progressive supranuclear palsy (PSP), the maximal amplitude of ocular movement has not been quantitatively assessed despite of accumulating evidences of oculomotor dysfunction in Parkinson's disease (PD). Here, we evaluated the maximal oculomotor range and its response to levodopa in PD, and compare findings to atypical parkinsonism. Methods: We recruited 159 healthy controls (HC) as well as 154 PD, 30 PSP, and 16 multiple system atrophy (MSA) patients. Oculomotor range was assessed using a kinetic perimeter-adapted device for the vertical and horizontal axes (four positions). Parameters were reassessed after levodopa challenge and compared among PD, PSP, and MSA patients. Results: Maximum oculomotor range in PD patients was reduced as compared to HC. Levodopa improved oculomotor range in all directions; corrective effects of upward range positively correlated with improvements in Unified Parkinson's Disease Rating Scale III and bradykinesia sub-scores among PD patients. Although oculomotor range was markedly restricted among PSP and MSA patients, the beneficial effects of levodopa was less pronounced. Reduced oculomotor range of motion was more significant among PSP as compared to PD or MSA patients; MSA patients did not significantly differ from PD patients. The range of upward gaze was optimally sensitive for differentiating among PD, PSP, and MSA patients. Conclusion: Maximum oculomotor range was reduced among PD patients significantly improved by levodopa treatment. Variations in, as well as the positively effects of levodopa on, the range of upward gaze assist diagnostic differentiation among PD, PSP, and MSA patients. [ABSTRACT FROM AUTHOR]