Brain-first forms of Parkinson's disease are over-represented in patients with non-responsive resting tremor.

Motor subtypes in Parkinson's Disease (PD) are unstable over time, limiting mechanistic insights and biomarker discovery. We focused on Rest Tremor (RT) as a symptom to test for phenotype stability and link it to specific circuits and disease mechanisms. Using the PPMI cohort data over 5 years we found that RT is more stable than classical Tremor-Dominant definitions, a stability also seen for RT response to therapy. At time of diagnosis, the population of therapy-resistant RT patients was enriched with a brain-first PD profile as predicted by a-Synuclein origin site and connectome (SOC) model. Resistant-RT patients have lower gastrointestinal and cardiovascular symptoms, lower prevalence of probable REM-Sleep behaviour disorder, and higher dopaminergic asymmetry compared to therapy-responsive or no tremor patients. Treating RT as a distinct phenomenon revealed a relative phenotypic stability with treatment response being linked to different patterns of disease progression.

Peripubertal exposure of atrazine cause decrease in exploratory activity, deficits in sociability and few alterations on brain monoaminergic systems of rats.

Atrazine is a pesticide used to control weeds in both in pre- and post-emergence crops. The chronic exposure to atrazine can lead to severe damage in animals, especially in the endocrine and reproduction systems, leading to the inclusion of this pesticide into the endocrine disrupting chemicals group. Studies with rats showed that atrazine exposure during lactation in dams caused changes in the juvenile offspring, however; there is still limited information regarding the effects of atrazine during puberty. Thus, the aim of this study is to evaluate the effects of peripubertal exposure of atrazine in rats, assessing motor activity, social behavior and neurochemical alterations. Juvenile rats were treated with different doses of atrazine (0, 10, 30 or 100 mg/kg) by gavage from postnatal day 22 to 41. Behavioral tests were conducted for the evaluation of motor activity and social behavior, and neurochemical evaluation was done in order to assess monoamine levels. Atrazine caused behavioral alterations, evidenced by decrease in the exploratory activity (p values variation between 0.05 and 0.0001) and deficits in the social behavior of both male and females as adults (p values variation between 0.01 and 0.0001). As for the monoaminergic neurotransmission, atrazine led to very few alterations on the dopamine and serotonin systems that were limited to the females (p < 0.05). Altogether, the results suggests that peripubertal exposure of atrazine cause behavioral and neurochemical alterations. More studies need to be conducted to fully understand the differences in atrazine's effects and its use should be considered carefully.

Combined antibodies against internalins A and B proteins have potential application in immunoassay for detection of Listeria monocytogenes.

Listeria monocytogenes is a food-borne bacterium that causes listeriosis upon the ingestion of contaminated food. Traditional methods to detect L. monocytogenes require pre-enrichment broths to increase its concentration. To improve the screening of contaminated food and prevent listeriosis outbreaks, rapid, specific and sensitive assays are needed to detect L. monocytogenes. This study developed a prototype lateral flow immunochromatographic assay (LFIA) employing antibodies against L. monocytogenes Internalin A (InlA) and Internalin B (InlB) proteins, that are involved in non-phagocytic cell invasion. The following antibodies were used to capture L. monocytogenes antigenic targets: mouse anti-Internalin A monoclonal antibody (MAb-2D12) conjugated to colloidal gold nanoparticles and a mouse anti-Internalin B polyclonal antibody. This test was able to detect pure L. monocytogenes from culture with a limit of detection (LOD) ranging from 5.9 × 103 to 1.5 × 104 CFU/mL. In milk artificially contaminated with L. monocytogenes, the LOD was 1 × 105 CFU/mL. This prototype test discriminated L. monocytogenes from other bacterial species (Listeria innocua, Enterobacter cloacae, Bacillus cereus). Results indicate that this LFIA developed using antibodies against L. monocytogenes InlA and InlB proteins is a sensitive and specific tool that can be potentially useful to rapidly detect L. monocytogenes in contaminated food. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05597-9.

Distinct gait dimensions are modulated by physical activity in Parkinson's disease patients.

Parkinson's disease (PD) is the fastest growing neurodegenerative disease, but disease-modifying or preventive treatments are lacking. Physical activity is a modifiable factor that decreases the PD risk and improves motor symptoms in PD. Understanding which dimensions of gait performance correlate with physical activity in PD can have important pathophysiological and therapeutic implications. Clinical/demographic data together with physical activity levels were collected from thirty-nine PD patients. Gait analysis was performed wearing seven inertial measurement units on the lower body, reconstructing the subjects' lower body motion using 3D kinematic biomechanical models. Higher physical activity scores were significantly correlated with MDS-UPDRS part III scores (r = - 0.58, p value = 9.2 × 10-5), age (r = - 0.39, p value = 1.5 × 10-2) and quality-of-life (r = - 0.47, p value = 5.9 × 10-3). Physical activity was negatively associated with MDS-UPDRS part III scores after adjusting for age and disease duration (ß = - 0.08530, p value = 0.0010). The effect of physical activity on quality-of-life was mediated by the MDS-UPDRS part III (62.10%, 95% CI = 0.0758-1.78, p value = 0.022). The level of physical activity was correlated primarily with spatiotemporal performance. While spatiotemporal performance displays the strongest association with physical activity, other quality-of-movement dimensions of clinical relevance (e.g., smoothness, rhythmicity) fail to do so. Interventions targeting these ought to be leveraged for performance enhancement in PD through neuroprotective and brain network connectivity strengthening. It remains to be ascertained to which extent these are amenable to modulation.

Listeria monocytogenes: review of pathogenesis and virulence determinants-targeted immunological assays.

Listeria monocytogenes is one of the most invasive foodborne pathogens and is responsible for numerous outbreaks worldwide. Most of the methods to detect this bacterium in food require selective enrichment using traditional bacterial culture techniques that can be time-consuming and labour-intensive. Moreover, molecular methods are expensive and need specific technical knowledge. In contrast, immunological approaches are faster, simpler, and user-friendly alternatives and have been developed for the detection of L. monocytogenes in food, environmental, and clinical samples. These techniques are dependent on the constitutive expression of L. monocytogenes antigens and the specificity of the antibodies used. Here, updated knowledge on pathogenesis and the key immunogenic virulence determinants of L. monocytogenes that are used for the generation of monoclonal and polyclonal antibodies for the serological assay development are summarised. In addition, immunological approaches based on enzyme-linked immunosorbent assay, immunofluorescence, lateral flow immunochromatographic assays, and immunosensors with relevant improvements are highlighted. Though the sensitivity and specificity of the assays were improved significantly, methods still face many challenges that require further validation before use.

REM sleep behaviour disorder in essential tremor: A polysomnographic study.

Our objectives were to assess the prevalence of REM sleep behaviour disorder in patients with Essential Tremor, using video-polysomnography and to compare REM sleep behaviour disorder features in essential tremor with those of patients with alpha-synucleinopathies. Forty-nine patients with essential tremor were screened with the REM Sleep Behaviour Disorder Screening Questionnaire. Patients scoring positive and those with spontaneous complaints of REM sleep behaviour disorder (n = 6) underwent video-polysomnography. The clinical features of essential tremor were compared between patients with and without REM sleep behaviour disorder. Video-polysomnography data were compared between patients who had essential tremor and Parkinson's disease with REM sleep behaviour disorder and those with idiopathic REM sleep behaviour disorder. Fourteen patients (23.5%) screened positive for REM sleep behaviour disorder, confirmed by video-polysomnography in five (11.6%). All patients with essential tremor and REM sleep behaviour disorder had rest tremor, compared with 13 (34.2%) in the group with essential tremor but without REM sleep behaviour disorder (p = .009). In video-polysomnography, patients with essential tremor and REM sleep behaviour disorder were similar to patients with Parkinson's disease with REM sleep behaviour disorder and presented worse sleep dysfunction and lower severity of REM sleep behaviour disorder compared to those with idiopathic REM sleep behaviour disorder. We found a high prevalence of REM sleep behaviour disorder in patients with essential tremor, associated with a predominance of rest tremor. Polysomnography data from patients with essential tremor and REM sleep behaviour disorder were similar to those in patients with Parkinson's disease. This suggests a relation between this subgroup of patients with essential tremor and the alpha-synucleinopathies.

Naringenin-Functionalized Multi-Walled Carbon Nanotubes: A Potential Approach for Site-Specific Remote-Controlled Anticancer Delivery for the Treatment of Lung Cancer Cells.

Multi-walled carbon nanotubes functionalized with naringenin have been developed as new drug carriers to improve the performance of lung cancer treatment. The nanocarrier was characterized by Transmission Electron Microscopy (TEM), Fourier-Transform Infrared Spectroscopy (FTIR), X-ray photoelectron spectroscopy, Raman Spectroscopy, and Differential Scanning Calorimetry (DSC). Drug release rates were determined in vitro by the dialysis method. The cytotoxic profile was evaluated using the MTT assay, against a human skin cell line (hFB) as a model for normal cells, and against an adenocarcinomic human alveolar basal epithelial (A569) cell line as a lung cancer in vitro model. The results demonstrated that the functionalization of carbon nanotubes with naringenin occurred by non-covalent interactions. The release profiles demonstrated a pH-responsive behavior, showing a prolonged release in the tumor pH environment. The naringenin-functionalized carbon nanotubes showed lower cytotoxicity on non-malignant cells (hFB) than free naringenin, with an improved anticancer effect on malignant lung cells (A549) as an in vitro model of lung cancer.

Cognitive complaints in Parkinson's disease patients: from subjective cognitive complaints to dementia and affective disorders.

Subjective cognitive complaints (SCC) are frequent in elderly populations. PD patients report SCC more often than healthy controls. The association between SCC, objective cognitive impairment and affective symptoms remains controversial. We assessed consecutive PD patients between March 2014 and March 2015. Presence of SCC was defined as a score ≥ 1 in the Non-Motor Symptom Assessment Scale for Parkinson's Disease (NMSS) Domain 5. MoCA was used for cognitive impairment assessment. Pill Questionnaire measured the impact in daily activities. PD with Dementia (PDD) and PD with Mild Cognitive Impairment (PDMCI) were defined as the presence of cognitive impairment with or without impact on daily activities. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scales. Significance was set at p < 0.05. From 134 patients, 128 were included. PDD was diagnosed in 21 (16.4%), PDMCI in 31 (24.2%), and 76 (59.4%) had normal cognition (PDCN). SCC were present in 85% of whole cohort and evenly distributed (p = 0.361), PDD (95.2%), PDMCI (83.9%) and PDCN (82.9%). Severity was significantly different between PDD (20.00 ± 10.81), PDMCI (6.54 ± 5.5) and PDCN (6.97 ± 6.98), p < 0.001. A score ≥ 19 had a specificity of 77.3% and a sensitivity of 78.8% for identifying PDD. In PDCN, SCC severity was found to be related to depression (OR 1.23, CI 95% 1.02-1.47, p = 0.026) more than with MoCA scores (OR: 0.86, CI 95% 0.69-1.05, p = 0.141). SCC are common in PD. Their severity can help distinguish PDD from non-demented PD patients. In PDCN, SCC should alert the clinician for an affective disorder.

Autonomic nervous system response to remote ischemic conditioning: heart rate variability assessment.

BACKGROUND: Remote ischemic conditioning (RIC) is a procedure applied in a limb for triggering endogenous protective pathways in distant organs, namely brain or heart. The underlying mechanisms of RIC are still not fully understood, and it is hypothesized they are mediated either by humoral factors, immune cells and/or the autonomic nervous system. Herein, heart rate variability (HRV) was used to evaluate the electrophysiological processes occurring in the heart during RIC and, in turn to assess the role of autonomic nervous system. METHODS: Healthy subjects were submitted to RIC protocol and electrocardiography (ECG) was used to evaluate HRV, by assessing the variability of time intervals between two consecutive heart beats. This is a pilot study based on the analysis of 18 ECG from healthy subjects submitted to RIC. HRV was characterized in three domains (time, frequency and non-linear features) that can be correlated with the autonomic nervous system function. RESULTS: RIC procedure increased significantly the non-linear parameter SD2, which is associated with long term HRV. This effect was observed in all subjects and in the senior (> 60 years-old) subset analysis. SD2 increase suggests an activation of both parasympathetic and sympathetic nervous system, namely via fast vagal response (parasympathetic) and the slow sympathetic response to the baroreceptors stimulation. CONCLUSIONS: RIC procedure modulates both parasympathetic and sympathetic autonomic nervous system. Furthermore, this modulation is more pronounced in the senior subset of subjects. Therefore, the autonomic nervous system regulation could be one of the mechanisms for RIC therapeutic effectiveness.

Effect of patients' expectations on clinical response to fampridine treatment.

INTRODUCTION: Patient expectation of treatment outcome is one of the primary mechanisms underlying the placebo effect. In multiple sclerosis trials with symptomatic treatments, a robust placebo effect is observed, which might be related to patient expectations. The aim of this study was to evaluate whether patient expectations regarding fampridine treatment influence the clinical response after 4 weeks and 6 months of treatment. MATERIALS AND METHODS: We designed and carried out a prospective study from June 2015 to August 2017. Before treatment, patients completed a questionnaire including a scale evaluating their expectations regarding the treatment. The effect of baseline positive expectancy on the response status after 4 weeks and 6 months of treatment was analyzed through univariable and, when applicable, multivariable analysis. RESULTS: A total of 47 consecutive patients were included in the study. At week 4, 37 (78.7%) patients were classified as responders; a one-point increase in the positive expectancy questionnaire was significantly associated with a fourfold increase in the likelihood of being a responder [OR = 4.020 (95% CI 1.082-14.933); p = 0.038]. At 6 months, 43 patients completed follow-up. The number of responders decreased to 28; at this point, positive expectancy at baseline was no longer associated with response status. CONCLUSION: Baseline positive expectancy regarding fampridine was determinant of the clinical response after 4 weeks of treatment. However, in the long term, fampridine efficacy was not dependent on expectations prior to treatment.

Beer Molecules and Its Sensory and Biological Properties: A Review.

The production and consumption of beer plays a significant role in the social, political, and economic activities of many societies. During brewing fermentation step, many volatile and phenolic compounds are produced. They bring several organoleptic characteristics to beer and also provide an identity for regional producers. In this review, the beer compounds synthesis, and their role in the chemical and sensory properties of craft beers, and potential health benefits are described. This review also describes the importance of fermentation for the brewing process, since alcohol and many volatile esters are produced and metabolized in this step, thus requiring strict control. Phenolic compounds are also present in beer and are important for human health since it was proved that many of them have antitumor and antioxidant activities, which provides valuable data for moderate dietary beer inclusion studies.

Heart rate variability in Parkinson disease and idiopathic REM sleep behavior disorder.

PURPOSE: Heart rate variability, a marker of autonomic function modulation, is known to be blunted in Parkinson disease, although data remains conflicting and a putative modifying role of REM sleep behavior disorder persists unclarified. METHODS: We assessed ten patients with idiopathic REM sleep behavior disorder patients, 18 patients with Parkinson disease and REM behavior disorder and eight patients with Parkinson disease without REM sleep behavior disorder. Heart rate variability analysis was performed in 5-min epochs selected from wake, Non-REM and REM polysomnography records. We compared heart rate variability measures by stage between two sets of groups: Parkinson disease vs. idiopathic RBD and patients with vs. without RBD, by using repeated measures ANOVA. RESULTS: There were no heart rate variability differences between Parkinson disease and idiopathic REM sleep behavior disorder groups. There were significant stage vs. group interactions (p = 0.045) regarding the high frequencies components when comparing patients with and without REM sleep behavior disorder, with the former presenting lower values and attenuation of sleep stage variations. CONCLUSION: Our study suggests that RBD is related with reduction in parasympathetic modulation of heart rate variability and blunting of sleep stage related variations.

Characterization of motor events in REM sleep behavior disorder.

We used video-polysomnography to characterize motor events (ME) in 14 Parkinson's disease (PD-RBD) and 18 idiopathic (iRBD) REM sleep behavior disorder cases. ME occurred predominantly in the upper limbs and were mostly simple, non-emotional, distal and focal. There were no significant differences in ME features between PD-RBD and iRBD groups. Our data suggests that RBD ME are mostly non violent. Similarity between PD-RBD and iRBD groups suggests that motor dysfunction does not affect ME features.

Motor and non-motor symptoms in old-age onset Parkinson's disease patients.

Advancing age is a well-known risk factor for Parkinson's disease (PD). With population ageing it is expected that the total number of patients with PD onset at oldage increases. Information on the motor but particularly on non-motor phenotype of this late-onset population is lacking. We recruited 24 patients with PD onset at or over 75 years. Each patient was matched with 1 control patient with PD onset between the ages of 40 and 65 and matched for disease duration. Both groups were assessed with the UPDRS, the Non-motor symptoms scale (NMSS) and other scales to assess non-motor symptoms. Groups were compared with conditional logistic regression analysis. Old-age onset PD was, on average, 80 years at the time of PD onset while middle-age onset were 59. Disease duration was approximately 5 years in both groups. While no difference was observed in the total UPDRS-III scores, old-age onset PD was associated with higher axial symptoms (7.42 vs. 4.63, p = 0.011) and a higher frequency of dementia (7/24 vs. 0/24, p = 0.009). While no difference in the total number of non-motor symptoms was observed (6.79 vs. 6.22, p = 0.310), old-age onset patients had a higher prevalence of gastrointestinal symptoms (20/24 vs. 12/24, p = 0.037). For the same disease duration, older age onset is associated with worse axial motor dysfunction and dementia in PD patients. Beside gastrointestinal symptoms, non-motor symptoms are not associated with age.

Steroid-responsive painful ophthalmoplegia: Tolosa-Hunt syndrome, Eales disease, or both?

Introduction Tolosa-Hunt syndrome (THS) is one of the most common 'benign' causes of painful ophthalmoplegia. Diagnosis is based on clinical and imaging findings and the exclusion of other causes because there is no specific biomarker for the syndrome. Eales disease, an idiopathic inflammatory venous disease that primarily affects the eye, can also affect the central (as stroke or myelitis) and peripheral nervous system. Case report We report the case of a 32-year-old woman with a subacute left ophthalmoplegia and evidence of a gadolinium-enhanced lesion suggesting an inflammatory granuloma that resolved within 48 hours after treatment with steroids. A diagnosis of THS was considered at this time. On a follow-up ophthalmological examination, a diagnosis of Eales disease with involvement of the left eye was made. The patient was treated successfully. Conclusion Eales disease could be a cause of painful ophthalmoplegia and may mimic THS. Long-term follow-up of patients diagnosed with THS may be necessary to exclude other diagnoses.

Herbal Supplements Association with Reversible Cerebral Vasoconstriction Syndrome: A Case Report.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a clinico-radiologic syndrome characterized by thunderclap headache and reversible multifocal arterial constrictions that resolves within 3 months. RCVS can be either spontaneous or related to a trigger; vasoactive drugs including over-the-counter medicine are common culprits. Nevertheless, there are sparse data on the association of herbal supplements in the genesis of unexplained RCVS. METHODS: We describe a case of RCVS with a temporal association with the consumption of a diet pill composed of green tea, L-carnitine, and conjugated linoleic acid. We reviewed the literature describing RCVS cases associated with consumption of herbal supplements or plants. RESULTS: A 50-year-old black woman presented at the emergency room with a thunderclap headache less than 1 week after beginning a new herbal supplement with weight loss purpose. Angiographic study revealed multiple arterial constriction of virtually all intracranial territories that were reversed 28 days later. The patient was discharged with minimal symptoms. From our review, we identified 5 previous reports of herbal product-related triggers. CONCLUSIONS: Different factors can trigger RCVS. Besides our case, at least 5 other nutraceutical products were described to be associated with the disorders, 3 of them in patients without any other clear cause. Clinicians should be aware of the possible role of herbal supplements in RCVS, and their use should be systematically assessed in large RCVS cohorts to clarify this association.

Association of depressive symptoms with allodynia in patients with migraine: A cross-sectional study.

Aims Migraine and depression have a strong association. We aimed to determine whether this relationship was particularly evident in migraineurs with allodynia. Methods A cross-sectional study was carried out of 98 consecutive patients with episodic migraine presenting for their first evaluation in an outpatient clinic. The participants completed a demographic questionnaire, the Allodynia Symptom Checklist and the Hospital Anxiety and Depression Scale (HADS). Results Among the migraineurs, 75 (77%) reported allodynia. Allodynia was associated with higher median HADS-Anxiety (9 vs. 6, p = 0.038) and HADS-Depression (6 vs. 4, p = 0.014) scores. In a multiple regression model, the HADS-Depression scores were independently associated with allodynia (odds ratio 1.236, 95% confidence interval 1.046-1.461). An increased severity of allodynia correlated with higher depression scores ( r = 0.224; p = 0.027). Conclusion Anxious and depressive symptoms are more common in migraineurs with allodynia than in those without allodynia. Further studies are necessary to clarify the relationship between depressive symptoms and allodynia, as well as its therapeutic implications in migraine.