A phase 4, open-label study to evaluate the safety and immunogenicity of DTaP5-HBV-IPV-Hib in children previously vaccinated with DTaP2-HBV-IPV-Hib or DTaP5-HBV-IPV-Hib (V419-016).

DTaP5-HBV-IPV-Hib (Vaxelis®) is a hexavalent combination vaccine (HV) indicated in infants and toddlers for the prevention of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive disease due to Haemophilus influenzae type b. Switching between HVs during the childhood vaccination series is sometimes necessary due to, for example, vaccine availability, health-care provider preference, and/or tender awards. The purpose of this study was to describe the safety, tolerability, and immunogenicity of a booster dose of Vaxelis® in participants who previously received a primary infant series of either DTaP2-HBV-IPV-Hib (Hexyon®) or Vaxelis®. Healthy participants approximately 11-13 months of age who previously received a two-dose primary series of Hexyon® (HHV group) or Vaxelis® (VVV group) all received a Vaxelis® booster dose. Immunogenicity was evaluated by measuring antibody levels to individual vaccine antigens approximately 30 days following booster vaccination. Safety was evaluated as the proportion of participants with adverse events (AEs). The proportions of participants with antibody-specific responses for antigens contained in both Vaxelis® and Hexyon® at 30 days post-toddler-booster vaccination with Vaxelis® were comparable between groups, and higher in the VVV group for Vaxelis® antigens PRN and FIM2/3. The overall proportions of participants with AEs were generally comparable between groups. Following a booster dose of Vaxelis®, immune responses were comparable between groups for all shared antigens, and higher in the VVV group for antigens found only in Vaxelis®. The booster was well tolerated in both groups. These data support the use of Vaxelis® as a booster in mixed HV regimens.

Interhemispheric imbalance and bradykinesia features in Parkinson's disease.

In patients with Parkinson's disease, the connectivity between the two primary motor cortices may be altered. However, the correlation between asymmetries of abnormal interhemispheric connections and bradykinesia features has not been investigated. Furthermore, the potential effects of dopaminergic medications on this issue remain largely unclear. The aim of the present study is to investigate the interhemispheric connections in Parkinson's disease by transcranial magnetic stimulation and explore the potential relationship between interhemispheric inhibition and bradykinesia feature asymmetry in patients. Additionally, we examined the impact of dopaminergic therapy on neurophysiological and motor characteristics. Short- and long-latency interhemispheric inhibition was measured in 18 Parkinson's disease patients and 18 healthy controls, bilaterally. We also assessed the corticospinal and intracortical excitability of both primary motor cortices. We conducted an objective analysis of finger-tapping from both hands. Correlation analyses were performed to explore potential relationships among clinical, transcranial magnetic stimulation and kinematic data in patients. We found that short- and long-latency interhemispheric inhibition was reduced (less inhibition) from both hemispheres in patients than controls. Compared to controls, finger-tapping movements in patients were slower, more irregular, of smaller amplitudes and characterized by a progressive amplitude reduction during movement repetition (sequence effect). Among Parkinson's disease patients, the degree of short-latency interhemispheric inhibition imbalance towards the less affected primary motor cortex correlated with the global clinical motor scores, as well as with the sequence effect on the most affected hand. The greater the interhemispheric inhibition imbalance towards the less affected hemisphere (i.e. less inhibition from the less to the most affected primary motor cortex than that measured from the most to the less affected primary motor cortex), the more severe the bradykinesia in patients. In conclusion, the inhibitory connections between the two primary motor cortices in Parkinson's disease are reduced. The interhemispheric disinhibition of the primary motor cortex may have a role in the pathophysiology of specific bradykinesia features in patients, i.e. the sequence effect.

Theta-tACS modulates cerebellar-related motor functions and cerebellar-cortical connectivity.

OBJECTIVE: To evaluate the effects of cerebellar transcranial alternating current stimulation (tACS) delivered at cerebellar-resonant frequencies, i.e., theta (θ) and gamma (γ), on upper limb motor performance and cerebellum-primary motor cortex (M1) connectivity, as assessed by cerebellar-brain inhibition (CBI), in healthy subjects. METHODS: Participants underwent cerebellar-tACS while performing three cerebellar-dependent motor tasks: (i) rhythmic finger-tapping, (ii) arm reaching-to-grasp ('grasping') and (iii) arm reaching-to-point ('pointing') an object. Also, we evaluated possible changes in CBI during cerebellar-tACS. RESULTS: θ-tACS decreased movement regularity during the tapping task and increased the duration of the pointing task compared to sham- and γ-tACS. Additionally, θ-tACS increased the CBI effectiveness (greater inhibition). The effect of θ-tACS on movement rhythm correlated with CBI changes and less tapping regularity corresponded to greater CBI. CONCLUSIONS: Cerebellar-tACS delivered at the θ frequency modulates cerebellar-related motor behavior and this effect is, at least in part, mediated by changes in the cerebellar inhibitory output onto M1. The effects of θ-tACS may be due to the modulation of cerebellar neurons that resonate to the θ rhythm. SIGNIFICANCE: These findings contribute to a better understanding of the physiological mechanisms of motor control and provide new evidence on cerebellar non-invasive brain stimulation.

Prenatal Findings in Postnatal Cases of Disorders of Sex Development: Experience from a Tertiary-Specialized Center in Brazil.

INTRODUCTION AND OBJECTIVE: Prenatal suspicion of disorders/differences of sex development (DSDs) is a relatively new phenomenon. The aim of this study was to review the prenatal findings of DSD cases postnatally diagnosed in our tertiary referral center. METHODS: We evaluated 57 DSD cases with sex ambiguity who had undergone prenatal ultrasound with phenotypic sex assessment and/or cell-free fetal DNA (cffDNA) for genotypic sex assessment. RESULTS: Prenatal cffDNA had been performed in 32 cases, being positive (suggestive of male genotypic sex) in 26 and negative (suggestive of female genotypic sex) in 6. Five with cffDNA negative had a prenatal ultrasound indicating female external genitalia, in turn, in those with cffDNA positive, only two had a prenatal ultrasound indicating male external genitalia. Our postnatal data showed that when external genitalia were female or poorly virilized, prenatal ultrasound indicated female sex, but in cases of higher degree of virilization, ultrasound showed similar rates of male, female, or undetermined sex. Regarding the karyotype, our data showed those with XY karyotype had positive cffDNA, those with XX karyotype had negative cffDNA, and all five with sex chromosome anomalies had positive cffDNA because they were 45,X/46,XY. We suggested an algorithm to investigate these cases during gestation, including evaluation of uterus, fetal growth, and malformations. CONCLUSION: We suggest that the parents should be counseled prenatally by a dedicated multidisciplinary team with experience in DSD management and evaluated as soon as possible after birth.

Facial emotion expressivity in patients with Parkinson's and Alzheimer's disease.

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders with some overlapping clinical features. Hypomimia (reduced facial expressivity) is a prominent sign of PD and it is also present in AD. However, no study has experimentally assessed hypomimia in AD and compared facial expressivity between PD and AD patients. We compared facial emotion expressivity in patients with PD, AD, and healthy controls (HCs). Twenty-four PD patients, 24 AD patients and 24 HCs were videotaped during neutral facial expressions and while posing six facial emotions (anger, surprise, disgust, fear, happiness, and sadness). Fifteen raters were asked to evaluate the videos using MDS-UPDRS-III (item 3.2) and to identify the corresponding emotion from a seven-forced-choice response format. We measured the percentage of accuracy, the reaction time (RT), and the confidence level (CL) in the perceived accuracy of the raters' responses. We found the highest MDS-UPDRS 3.2 scores in PD, and higher in AD than HCs. When evaluating the posed expression captures, raters identified a lower percentage of correct answers in the PD and AD groups than HCs. There was no difference in raters' response accuracy between the PD and AD. No difference was observed in RT and CL data between groups. Hypomimia in patients correlated positively with the global MDS-UPDRS-III and negatively with Mini Mental State Examination scores. PD and AD patients have a similar pattern of reduced facial emotion expressivity compared to controls. These findings hold potential pathophysiological and clinical implications.

Deep brain stimulation of globus pallidus internus and subthalamic nucleus in Parkinson's disease: a multicenter, retrospective study of efficacy and safety.

BACKGROUND: Deep brain stimulation (DBS) is an established therapeutic option in advanced Parkinson's disease (PD). Literature data and recent guidelines remain inconclusive about the best choice as a target between the subthalamic nucleus (STN) and the globus pallidus internus (GPi). MATERIALS AND METHODS: We retrospectively reviewed the clinical efficacy outcomes of 48 DBS-implanted patients (33 STN-DBS and 15 GPi-DBS) at a short- (<1 year from the surgery) and long-term (2-5 years) follow-up. Also, clinical safety outcomes, including postoperative surgical complications and severe side effects, were collected. RESULTS: We found no difference between STN-DBS and GPi-DBS in improving motor symptoms at short-term evaluation. However, STN-DBS achieved a more prominent reduction in oral therapy (L-DOPA equivalent daily dose, P = .02). By contrast, GPi-DBS was superior in ameliorating motor fluctuations and dyskinesia (MDS-UPDRS IV, P < .001) as well as motor experiences of daily living (MDS-UPDRS II, P = .03). The greater efficacy of GPi-DBS on motor fluctuations and experiences of daily living was also present at the long-term follow-up. We observed five serious adverse events, including two suicides, all among STN-DBS patients. CONCLUSION: Both STN-DBS and GPi-DBS are effective in improving motor symptoms severity and complications, but GPi-DBS has a greater impact on motor fluctuations and motor experiences of daily living. These results suggest that the two targets should be considered equivalent in motor efficacy, with GPi-DBS as a valuable option in patients with prominent motor complications. The occurrence of suicides in STN-treated patients claims further attention in target selection.

Objective assessment of the effects of opicapone in Parkinson's disease through kinematic analysis.

BACKGROUND: Opicapone (OPC) is a third-generation, selective peripheral COMT inhibitor that improves peripheral L-DOPA bioavailability and reduces OFF time and end-of-dose motor fluctuations in Parkinson's disease (PD) patients. OBJECTIVES: In this study, we objectively assessed the effects of adding OPC to L-DOPA on bradykinesia in PD through kinematic analysis of finger movements. METHODS: We enrolled 20 treated patients with PD and motor fluctuations. Patients underwent two experimental sessions (L-DOPA, L-DOPA + OPC), separated by at least 1 week. In each session, patients were clinically evaluated and underwent kinematic movement analysis of repetitive finger movements at four time points: (i) before their usual morning dose of L-DOPA (T0), (ii) 30 min (T1), (iii) 1 h and 30 min (T2), and (iv) 3 h and 30 min after the L-DOPA intake (T3). RESULTS: Movement velocity and amplitude of finger movements were higher in PD patients during the session with OPC compared to the session without OPC at all the time points tested. Importantly, the variability of finger movement velocity and amplitude across T0-T3 was significantly lower in the L-DOPA + OPC than L-DOPA session. CONCLUSIONS: This study is the first objective assessment of the effects of adding OPC to L-DOPA on bradykinesia in patients with PD and motor fluctuations. OPC, in addition to the standard dopaminergic therapy, leads to significant improvements in bradykinesia during clinically relevant periods associated with peripheral L-DOPA dynamics, i.e., the OFF state in the morning, delayed-ON, and wearing-OFF periods.

DHX37 and the implications in Disorders of Sex Development: an update review.

BACKGROUND: DHX37 is an autosomal gene responsible for encoding a helicase from the DExD/H-box family that plays an essential role in ribosome biogenesis. Variants in this gene were previously reported in two different phenotypes: neurodevelopmental disorders and disorders/differences of sex development (DSD). Particularly for the DSD group, variants were mainly reported associated with gonadal dysgenesis and testicular regression syndrome. SUMMARY: Focusing specific in the DSD group, we revised the 21 DHX37 variants described across a total of 55 cases published in the literature so far. We summarized the most important clinical and molecular features of all cases, trying to have a better comprehensiveness about this gene in the sexual development. KEY MESSAGES: The trick question regarding DHX37 is how a helicase involved in basic cell function could have a specific role in testis development. Little is known about the impact of DHX37 variants in DSD individuals. Nevertheless, current research strongly suggests that DHX37 is involved in the male sex development pathway, particularly in testis determination and maintenance. This is evidenced by the predominant assignment of affected individuals as males and the presence of Wolffian structures in most of the cases. Advancements in molecular techniques, such as the generation of induced pluripotent stem cells, and the digenic inheritance for DHX37 cases, are also addressed in this paper. This represents the first comprehensive review of all DHX37 variants published in the literature to date.

Racismo e Sexismo: Estruturas de Transmissão, Incidências da História e Insistências do Real / Racism and Sexism: Transmission Structures, History Incidences and Insistences of the Real / Racismo y Sexismo: Estructuras de Transmisión, Incidencias de la Historia e Insistencias de lo Real

Este artigo propõe articulações entre as estruturas coloniais de incidência do racismo e do sexismo no laço social e suas vias de inscrição no inconsciente e no corpo. Partimos de um debate sobre o enquadre colonial da subjetividade e de questões levantadas por Frantz Fanon acerca do modo como o racismo se conecta com a lógica fálica do complexo de Édipo para avaliar sua validade em relação à realidade de povos colonizados. Retomamos formulações freudianas e lacanianas úteis para abordar essa encruzilhada, a partir dos caminhos apontados por Lélia Gonzalez ao discutir as subversões operadas pela mulher negra diante do racismo e do sexismo no contexto brasileiro. Com base em alguns fragmentos clínicos, sustentamos que uma abordagem clínica da perspectiva interseccional antecipada por Lélia Gonzalez demanda uma tomada dialética das relações entre estrutura e história, entre o coletivo e o singular e entre o inconsciente colonizado e o resto que escapa e subverte as relações de dominação.

This article proposes articulations between the colonial structures of incidence of the racism and sexism in the social bond and their ways of inscription in the unconscious and in the body. Starting from a debate about the colonial framework of subjectivity and from questions raised by Frantz Fanon about how the racism connects with the phallic logic of the Oedipus complex to assess its validity in relation to the reality of colonized peoples. We return to useful Freudian and Lacanian formulations to address this crossroads, based on the paths pointed out by Lélia Gonzalez when discussing the subversions operated by black women in the face of racism and sexism in the Brazilian context. Based on some clinical fragments, we argue that a clinical approach to the intersectional perspective anticipated by Lélia Gonzalez demands a dialectical approach to the relations between structure and history, between the collective and the singular, and between the colonized unconscious and the rest that escapes and subverts the relations of domination.

Este artículo propone articulaciones entre las estructuras coloniales de incidencia del racismo y del sexismo en el lazo social y sus formas de inscripción en el inconsciente y en el cuerpo. Partimos de un debate sobre el marco colonial de la subjetividad y de las preguntas planteadas por Frantz Fanon sobre la forma en que el racismo se relaciona con la lógica fálica del complejo de Edipo para evaluar su validez con relación a la realidad de los pueblos colonizados. Retomamos formulaciones freudianas y lacanianas útiles para abordar esta encrucijada, a partir de los caminos señalados por Lélia González al discutir las subversiones operadas por las mujeres negras frente al racismo y al sexismo en el contexto brasileño. En función de algunos fragmentos clínicos, sostenemos que una aproximación clínica de la perspectiva interseccional, anticipada por Lélia González, exige un abordaje dialéctico de las relaciones entre estructura e historia, entre lo colectivo y lo singular y entre el inconsciente colonizado y el resto que escapa y subvierte las relaciones de dominación.

Band-Specific Altered Cortical Connectivity in Early Parkinson's Disease and its Clinical Correlates.

BACKGROUND: Functional connectivity (FC) has shown promising results in assessing the pathophysiology and identifying early biomarkers of neurodegenerative disorders, such as Parkinson's disease (PD). OBJECTIVES: In this study, we aimed to assess possible resting-state FC abnormalities in early-stage PD patients using high-density electroencephalography (EEG) and to detect their clinical relationship with motor and non-motor PD symptoms. METHODS: We enrolled 26 early-stage levodopa naïve PD patients and a group of 20 healthy controls (HC). Data were recorded with 64-channels EEG system and a source-reconstruction method was used to identify brain-region activity. FC was calculated using the weighted phase-lag index in θ, α, and ß bands. Additionally, we quantified the unbalancing between ß and lower frequencies through a novel index (ß-functional ratio [FR]). Statistical analysis was conducted using a network-based statistical approach. RESULTS: PD patients showed hypoconnected networks in θ and α band, involving prefrontal-limbic-temporal and frontoparietal areas, respectively, and a hyperconnected network in the ß frequency band, involving sensorimotor-frontal areas. The θ FC network was negatively related to Non-Motor Symptoms Scale scores and α FC to the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III gait subscore, whereas ß FC and ß-FR network were positively linked to the bradykinesia subscore. Changes in θ FC and ß-FR showed substantial reliability and high accuracy, precision, sensitivity, and specificity in discriminating PD and HC. CONCLUSIONS: Frequency-specific FC changes in PD likely reflect the dysfunction of distinct cortical networks, which occur from the early stage of the disease. These abnormalities are involved in the pathophysiology of specific motor and non-motor PD symptoms, including gait, bradykinesia, mood, and cognition. © 2023 International Parkinson and Movement Disorder Society.

Remote monitoring of implantable cardiac monitors in patients with unexplained syncope: Predictors of false-positive alert episodes.

BACKGROUND: Remote monitoring is recommended for patients with implantable cardiac monitors (ICMs), but compared to other cardiac implantable devices, ICMs are less accurate and transmit a higher number of alerts. OBJECTIVE: The aim of this study was to investigate the predictors of false-positive (FP) arrhythmic alerts in patients with unexplained syncope who were implanted with ICM and followed by an automatic remote monitoring system. METHODS: We retrospectively evaluated all consecutive patients who received a long-sensing vector ICM for unexplained syncope between January 2019 to September 2021 at our Syncope Unit. The primary endpoint was the incidence of the first FP episode. The secondary endpoints included assessing the incidence of FP episodes for all types of algorhythms and indentifying the reasons for the misdetection of these episodes. RESULTS: Among 105 patients (44.8% males, median age 51 years), 51 (48.6%) transmitted at least one FP alert during a median follow-up of 301 days. The presence of pre-ventricular complexes (PVCs) on the resting electrocardiogram was the only clinical characteristic associated with an increased risk of FP alerts (adjusted Hazard ratio [HR] 5.76 [2.66-12.4], p = 0.010). The other significant device-related variables were a low-frequency filter at 0.05 Hz versus the default 0.5 Hz (adjusted HR 3.82 [1.38-10.5], p = 0.010) and the R-wave amplitude (adjusted HR 0.35 [0.13-0.99], p = 0.049). CONCLUSION: Patients who have PVCs are at higher risk of inappropriate ICM activations. To reduce the occurrence of FP alerts, it may be beneficial to target a large R-wave amplitude during device insertion and avoid programming a low-frequency filter at 0.05 Hz.

Subtle changes in central dopaminergic tone underlie bradykinesia in essential tremor.

INTRODUCTION: In this research, our primary objective was to explore the correlation between basal ganglia dopaminergic neurotransmission, assessed using 123I-FP-CIT (DAT-SPECT), and finger movements abnormalities in patients with essential tremor (ET) and Parkinson's disease (PD). METHODS: We enrolled 16 patients with ET, 17 with PD, and 18 healthy controls (HC). Each participant underwent comprehensive clinical evaluations, kinematic assessments of finger tapping. ET and PD patients underwent DAT-SPECT imaging. The DAT-SPECT scans were subjected to both visual and semi-quantitative analysis using DaTQUANT®. We then investigated the correlations between the clinical, kinematic, and DAT-SPECT data, in patients. RESULTS: Our findings confirm that individuals with ET exhibited slower finger tapping than HC. Visual evaluation of radiotracer uptake in both striata demonstrated normal levels within the ET patient cohort, while PD patients displayed reduced uptake. However, there was notable heterogeneity in the quantification of uptake within the striata among ET patients. Additionally, we found a correlation between the amount of radiotracer uptake in the striatum and movement velocity during finger tapping in patients. Specifically, lower radioligand uptake corresponded to decreased movement velocity (ET: coef. = 0.53, p-adj = 0.03; PD: coef. = 0.59, p-adj = 0.01). CONCLUSION: The study's findings suggest a potential link between subtle changes in central dopaminergic tone and altered voluntary movement execution, in ET. These results provide further insights into the pathophysiology of ET. However, longitudinal studies are essential to determine whether the slight reduction in dopaminergic tone observed in ET patients represents a distinct subtype of the disease or could serve as a predictor for the clinical progression into PD.

Current and novel infusion therapies for patients with Parkinson's disease.

Advanced Parkinson's disease is characterized by periods of poor mobility, dyskinesia and progressive decline in functional independence of the affected person despite the manipulation of levodopa doses and the introduction of supplemental therapies such as catechol-O-methyl transferase inhibitors, monoamine oxidase-B inhibitors and dopamine agonists. The implementation of drug delivery systems allows to bypass problems related to irregular and often unpredictable intestinal absorption of oral levodopa, which significantly affects its bioavailability and contributes to the development and persistence of motor complications. Subcutaneous apomorphine and levodopa/carbidopa jejunal infusion systems have been available for many years and their efficacy is confirmed by randomized studies and long-term experience in many centers worldwide. Recently, a new formulation of levodopa/carbidopa infusion gel that includes the catechol-O-methyl transferase inhibitor Entacapone has been introduced to the market. The use of entacapone allows to reduce total daily dose of administered levodopa. Two different soluble formulations of levodopa/carbidopa (ND0612 and ABBV-951) have completed clinical development, and both can ensure subcutaneous delivery by a portable pump infusion system. ABBV-951 uses a foslevodopa/foscarbidopa formulation, both prodrugs to improve absorption and tolerability. Both systems provide effective improvement of motor complications and are likely to expand the therapeutic options in advanced patients. Future efforts should focus on the earlier detection of patients who are candidates for device-aided therapies, increasing appropriate referral and broadening the availability of these treatments globally.

May Bradykinesia Features Aid in Distinguishing Parkinson's Disease, Essential Tremor, And Healthy Elderly Individuals?

BACKGROUND: Bradykinesia is the hallmark feature of Parkinson's disease (PD); however, it can manifest in other conditions, including essential tremor (ET), and in healthy elderly individuals. OBJECTIVE: Here we assessed whether bradykinesia features aid in distinguishing PD, ET, and healthy elderly individuals. METHODS: We conducted simultaneous video and kinematic recordings of finger tapping in 44 PD patients, 69 ET patients, and 77 healthy elderly individuals. Videos were evaluated blindly by expert neurologists. Kinematic recordings were blindly analyzed. We calculated the inter-raters agreement and compared data among groups. Density plots assessed the overlapping in the distribution of kinematic data. Regression analyses and receiver operating characteristic curves determined how the kinematics influenced the likelihood of belonging to a clinical score category and diagnostic group. RESULTS: The inter-rater agreement was fair (Fleiss K = 0.32). Rater found the highest clinical scores in PD, and higher scores in ET than healthy elderly individuals (p < 0.001). In regard to kinematic analysis, the groups showed variations in movement velocity, with PD presenting the slowest values and ET displaying less velocity than healthy elderly individuals (all ps < 0.001). Additionally, PD patients showed irregular rhythm and sequence effect. However, kinematic data significantly overlapped. Regression analyses showed that kinematic analysis had high specificity in differentiating between PD and healthy elderly individuals. Nonetheless, accuracy decreased when evaluating subjects with intermediate kinematic values, i.e., ET patients. CONCLUSION: Despite a considerable degree of overlap, bradykinesia features vary to some extent in PD, ET, and healthy elderly individuals. Our findings have implications for defining bradykinesia and categorizing patients.

Remote monitoring of implantable loop recorders reduces time to diagnosis in patients with unexplained syncope: a multicenter propensity score-matched study.

Background: There are little data on remote monitoring (RM) of implantable loop recorders (ILRs) in patients with unexplained syncope and whether it confers enhanced diagnostic power. Objective: To evaluate the effect of RM in ILR recipients for unexplained syncope for early detection of clinically relevant arrhythmias by comparison with a historical cohort with no RM. Methods: SyncRM is a propensity score (PS)-matched study prospectively including 133 consecutive patients with unexplained syncope and ILR followed up by RM (RM-ON group). A historical cohort of 108 consecutive ILR patients with biannual in-hospital follow-up visits was used as control group (RM-OFF group). The primary endpoint was the time to the clinician's evaluation of clinically relevant arrhythmias (types 1, 2, and 4 of the ISSUE classification). Results: The primary endpoint of arrhythmia evaluation was reached in 38 patients (28.6%) of the RM-ON group after a median time of 46 days (interquartile range, 13-106) and in 22 patients (20.4%) of the RM-OFF group after 92 days (25-368). The PS-matched adjusted ratio of rates of arrhythmia evaluation was 2.53 (95% confidence interval, 1.32-4.86) in the RM-ON vs. RM-OFF group (p = 0.005). Conclusion: In our PS-matched comparison with a historical cohort, RM of ILR patients with unexplained syncope was associated with a 2.5-fold higher chance of evaluations of clinically relevant arrhythmias as compared with biannual in-office follow-up visits.

Objective measurement versus clinician-based assessment for Parkinson's disease.

INTRODUCTION: Although clinician-based assessment through standardized clinical rating scales is currently the gold standard for quantifying motor impairment in Parkinson's disease (PD), it is not without limitations, including intra- and inter-rater variability and a degree of approximation. There is increasing evidence supporting the use of objective motion analyses to complement clinician-based assessment. Objective measurement tools hold significant potential for improving the accuracy of clinical and research-based evaluations of patients. AREAS COVERED: The authors provide several examples from the literature demonstrating how different motion measurement tools, including optoelectronics, contactless and wearable systems allow for both the objective quantification and monitoring of key motor symptoms (such as bradykinesia, rigidity, tremor, and gait disturbances), and the identification of motor fluctuations in PD patients. Furthermore, they discuss how, from a clinician's perspective, objective measurements can help in various stages of PD management. EXPERT OPINION: In our opinion, sufficient evidence supports the assertion that objective monitoring systems enable accurate evaluation of motor symptoms and complications in PD. A range of devices can be utilized not only to support diagnosis but also to monitor motor symptom during the disease progression and can become relevant in the therapeutic decision-making process.

DHX37 and NR5A1 Variants Identified in Patients with 46,XY Partial Gonadal Dysgenesis.

The group of disorders known as 46,XY gonadal dysgenesis (GD) is characterized by anomalies in testis determination, including complete and partial GD (PGD) and testicular regression syndrome (TRS). Several genes are known to be involved in sex development pathways, however approximately 50% of all cases remain elusive. Recent studies have identified variants in DHX37, a gene encoding a putative RNA helicase essential in ribosome biogenesis and previously associated with neurodevelopmental disorders, as a cause of PGD and TRS. To investigate the potential role of DHX37 in disorders of sexual development (DSD), 25 individuals with 46,XY DSD were analyzed and putative pathogenic variants were found in four of them. WES analyses were performed on these patients. In DHX37, the variant p.(Arg308Gln), recurrent associated with DSD, was identified in one patient; the p.(Leu467Val), predicted to be deleterious, was found together with an NR5A1 loss-of-function variant in patient 2; and, the p.(Val999Met) was identified in two unrelated patients, one of whom (patient 3) also carried a pathogenic NR5A1 variant. For both patients carrying DHX37 and NR5A1 pathogenic variants, a digenic inheritance is suggested. Our findings support the importance of DHX37 variants as a cause of disorders of sex development, implying a role in testis development.