Oculomotor Dysfunction in Idiopathic and LRRK2-Parkinson's Disease and At-Risk Individuals.

Background: Video-oculography constitutes a highly-sensitive method of characterizing ocular movements, which could detect subtle premotor changes and contribute to the early diagnosis of Parkinson's disease (PD). Objective: To investigate potential oculomotor differences between idiopathic PD (iPD) and PD associated with the G2019S variant of LRRK2 (L2PD), as well as to evaluate oculomotor function in asymptomatic carriers of the G2019S variant of LRRK2. Methods: The study enrolled 129 subjects: 30 PD (16 iPD, 14 L2PD), 23 asymptomatic carriers, 13 non-carrier relatives of L2PD patients, and 63 unrelated HCs. The video-oculographic evaluation included fixation, prosaccade, antisaccade, and memory saccade tests. Results: We did not find significant differences between iPD and L2PD. Compared to controls, PD patients displayed widespread oculomotor deficits including larger microsaccades, hypometric vertical prosaccades, increased latencies in all tests, and lower percentages of successful antisaccades and memory saccades. Non-carrier relatives showed oculomotor changes with parkinsonian features, such as fixation instability and hypometric vertical saccades. Asymptomatic carriers shared multiple similarities with PD, including signs of unstable fixation and hypometric vertical prosaccades; however, they were able to reach percentages of successful antisaccade and memory saccades similar to controls, although at the expense of longer latencies. Classification accuracy of significant oculomotor parameters to differentiate asymptomatic carriers from HCs ranged from 0.68 to 0.74, with BCEA, a marker of global fixation instability, being the parameter with the greatest classification accuracy. Conclusions: iPD and LRRK2-G2019S PD patients do not seem to display a differential oculomotor profile. Several oculomotor changes in asymptomatic carriers of LRRK2 mutations could be considered premotor biomarkers.

Lessons from Two Latino Communities Working with Academic Partners to Increase Access to COVID-19 Testing.

OBJECTIVE: We sought to examine the experiences of community partners in a community-academic partnership to promote COVID-19 testing in two majority Latino communities. METHODS: We conducted semistructured, in-depth interviews in English and Spanish with community-based organization leaders and community health workers/promotoras (n = 10) from June to July 2021. Interviews focused on identifying partner roles in planning and testing implementation and evaluating communication among partners. Interviews were transcribed and analyzed in ATLAS.ti version 8.4.5. Analyses involved deductive and inductive approaches to identify key themes. RESULTS: Participants described both strengths and challenges to the collaborative approach within each of three core themes: building relationships in the time of COVID-19; uplifting existing community leadership; and commitment of the academic partners and community-based organizations to conduct partnership activities in Spanish. CONCLUSION: Community-academic partnerships that invest in strong relationships, community leadership, and a commitment to the community's preferred language offer a promising approach to addressing COVID-19 testing barriers. Findings provide direction for future research on how community members and academic partners can come together to inform strategies to continue addressing the COVID-19 pandemic.

Septicemia due to Bacillus clausii after the use of probiotics. A complication to keep in mind. / Septicemia por Bacillus clausii posterior al uso de probióticos. Una complicación para tener presente.

Probiotics are live microorganisms that benefit the host in different clinical situations. Bacillus clausii is one of the most frequently used, but it is not without risk. To date, there are few reports of complications secondary to this agent in pediatric patients. OBJECTIVE: To describe the case of an infant who developed after treatment sepsis due to Bacillus clausii. CLINICAL CASE: A 4-month-old female infant of indigenous ethnicity, from a rural area in the interior of Panama, 3 hours away from the nearest health sub-center by canoe, and with protein-calorie malnutrition, presented with acute diarrhea and moderate-severe dehydration, receiving Enterogermina as part of the initial treatment. She was transferred to a tertiary hospital, where she arrived with impaired consciousness, respiratory distress, and signs of shock. The initial blood culture reported growth of methicillin-resistant Staphylococcus aureus (MRSA), the gastrointestinal panel was positive for Clostridiodes difficile, and later serial blood cultures of peripheral blood and central venous catheter confirmed growth of Bacillus clausii. With a torpid evolution and resistance to multiple antibiotic schemes, she died due to multisystem organ failure twelve days after admission. CONCLUSIONS: The use of probiotics as concomitant treatment in patients with some degree of immunosuppression should be administered with caution, considering the presence of risk criteria for complications such as malnutrition or intestinal epithelial damage due to severe diarrhea since they predispose to the development of bacteremia and/or sepsis.

Interactions between functional networks in Parkinson's disease mild cognitive impairment.

The study of mild cognitive impairment (MCI) is critical to understand the underlying processes of cognitive decline in Parkinson's disease (PD). Functional connectivity (FC) disruptions in PD-MCI patients have been observed in several networks. However, the functional and cognitive changes associated with the disruptions observed in these networks are still unclear. Using a data-driven methodology based on independent component analysis, we examined differences in FC RSNs among PD-MCI, PD cognitively normal patients (PD-CN) and healthy controls (HC) and studied their associations with cognitive and motor variables. A significant difference was found between PD-MCI vs PD-CN and HC in a FC-trait comprising sensorimotor (SMN), dorsal attention (DAN), ventral attention (VAN) and frontoparietal (FPN) networks. This FC-trait was associated with working memory, memory and the UPDRS motor scale. SMN involvement in verbal memory recall may be related with the FC-trait correlation with memory deficits. Meanwhile, working memory impairment may be reflected in the DAN, VAN and FPN interconnectivity disruptions with the SMN. Furthermore, interactions between the SMN and the DAN, VAN and FPN network reflect the intertwined decline of motor and cognitive abilities in PD-MCI. Our findings suggest that the memory impairments observed in PD-MCI are associated with reduced FC within the SMN and between SMN and attention networks.

Optical Encoding Model Based on Orbital Angular Momentum Powered by Machine Learning.

Based on orbital angular momentum (OAM) properties of Laguerre-Gaussian beams LG(p,ℓ), a robust optical encoding model for efficient data transmission applications is designed. This paper presents an optical encoding model based on an intensity profile generated by a coherent superposition of two OAM-carrying Laguerre-Gaussian modes and a machine learning detection method. In the encoding process, the intensity profile for data encoding is generated based on the selection of p and ℓ indices, while the decoding process is performed using a support vector machine (SVM) algorithm. Two different decoding models based on an SVM algorithm are tested to verify the robustness of the optical encoding model, finding a BER =10-9 for 10.2 dB of signal-to-noise ratio in one of the SVM models.

Switch to ocrelizumab in MS patients treated with natalizumab in extended interval dosing at high risk of PML: A 96-week follow-up pilot study.

We aimed to assess the long-term safety and effectiveness of ocrelizumab in a cohort of patients with multiple sclerosis (MS) at high risk of progressive multifocal leukoencephalopathy (PML), previously treated with natalizumab in extending interval dosing (EID), who switched to ocrelizumab and to compare them with patients who continued EID-natalizumab. Thirty MS patients previously treated with natalizumab in EID (every 8 weeks) were included in this observational retrospective cohort study. Among them, 17 patients were switched to ocrelizumab and 13 continued with EID-natalizumab. Except for the John Cunningham virus (JCV) index, no significant differences were detected between both groups. Main outcome measures included: annualized relapse rate (ARR), radiological activity, disability progression, and the NEDA-3 index. Patients were followed for 96 weeks. The median washout period in ocrelizumab-switchers was 6 weeks. Among them, AAR and radiological activity during follow-up were 0.03, without significant differences in comparison with the previous period on natalizumab-EID. The comparison between ocrelizumab-switchers and patients continuing on EID-natalizumab showed no significant differences in AAR, radiological activity, or disability progression. However, the proportion of patients maintaining a NEDA-3 status in week 96 was slightly superior among ocrelizumab-switchers (94 vs 69%). No serious adverse events were observed in any group. In conclusion, switching from EID-natalizumab to ocrelizumab can be considered as a therapeutic option, particularly in patients with MS at high risk of PML, to mitigate the risks of both PML and disease reactivation.

A novel clinical sign to assess the risk of Parkinson's disease in patients with isolated asymmetric arm swing.

INTRODUCTION: An isolated asymmetric arm swing can represent the beginning of Parkinson's disease (PD) but also be related to physiological or non-specific musculoskeletal pathology. PATIENTS AND METHODS: In this brief clinical observation including 15 patients with asymmetric arm swing, we provide a new clinical clue to evaluate the risk of subjacent parkinsonism. RESULTS: Among non-parkinsonian subjects, the immobilization of the contralateral arm, by asking the patient to put his hand on the contralateral shoulder, induced a clear increase in the amplitude of the arm swing, whereas in PD patients, the arm swing amplitude did not significantly vary when the contralateral upper limb was immobilized. CONCLUSIONS: This novel clinical sign may be helpful when approaching patients with gait abnormalities and specifically reduced arm swing.

Reproducibility and implementation of a rapid, community-based COVID-19 "test and respond" model in low-income, majority-Latino communities in Northern California.

OBJECTIVE: To evaluate implementation of a community-engaged approach to scale up COVID-19 mass testing in low-income, majority-Latino communities. METHODS: In January 2021, we formed a community-academic "Latino COVID-19 Collaborative" with residents, leaders, and community-based organizations (CBOs) from majority-Latinx, low-income communities in three California counties (Marin/Merced/San Francisco). The collaborative met monthly to discuss barriers/facilitators for COVID-19 testing, and plan mass testing events informed by San Francisco's Unidos en Salud "test and respond" model, offering community-based COVID-19 testing and post-test support in two US-census tracts: Canal (Marin) and Planada (Merced). We evaluated implementation using the RE-AIM framework. To further assess testing barriers, we surveyed a random sample of residents who did not attend the events. RESULTS: Fifty-five residents and CBO staff participated in the Latino collaborative. Leading facilitators identified to increase testing were extended hours of community-based testing and financial support during isolation. In March-April 2021, 1,217 people attended mass-testing events over 13 days: COVID-19 positivity was 3% and 1% in Canal and Planada, respectively. The RE-AIM evaluation found: census tract testing coverage of 4.2% and 6.3%, respectively; 90% of event attendees were Latino, 89% had household income <$50,000/year, and 44% first-time testers (reach), effectiveness in diagnosing symptomatic cases early (median isolation time: 7 days) and asymptomatic COVID-19 (41% at diagnosis), high adoption by CBOs in both counties, implementation of rapid testing (median: 17.5 minutes) and disclosure, and post-event maintenance of community-based testing. Among 265 non-attendees surveyed, 114 (43%) reported they were aware of the event: reasons for non-attendance among the 114 were insufficient time (32%), inability to leave work (24%), and perceptions that testing was unnecessary post-vaccination (24%) or when asymptomatic (25%). CONCLUSION: Community-engaged mass "test and respond" events offer a reproducible approach to rapidly increase COVID-19 testing access in low-income, Latinx communities.

Increasing access and uptake of SARS-CoV-2 at-home tests using a community-engaged approach.

Inequalities around COVID-19 testing and vaccination persist in the U.S. health system. We investigated whether a community-engaged approach could be used to distribute free, at-home, rapid SARS-CoV-2 tests to underserved populations. Between November 18-December 31, 2021, 400,000 tests were successfully distributed via 67 community partners and a mobile unit to a majority Hispanic/Latino/Spanish population in Merced County, California. Testing before gathering (59 %) was the most common testing reason. Asians versus Whites were more likely to test for COVID-19 if they had close contact with someone who may have been positive (odds ratio [OR] = 3.4, 95 % confidence interval [CI] = 1.7-6.7). Minors versus adults were more likely to test if they had close contact with someone who was confirmed positive (OR = 1.7, 95 % CI = 1.0-3.0), whereas Asian (OR = 4.1, 95 % CI = 1.2-13.7) and Hispanic/Latino/Spanish (OR = 2.5, 95 % CI = 1.0-6.6) versus White individuals were more likely to test if they had a positive household member. Asians versus Whites were more likely to receive a positive test result. Minors were less likely than adults to have been vaccinated (OR = 0.2, 95 % CI = 0.1-0.3). Among unvaccinated individuals, those who completed the survey in English versus Spanish indicated they were more likely to get vaccinated in the future (OR = 8.2, 95 % CI = 1.5-44.4). Asians versus Whites were less likely to prefer accessing oral COVID medications from a pharmacy/drug store only compared with a doctor's office or community setting (OR = 0.3, 95 % CI = 0.2-0.6). Study findings reinforce the need for replicable and scalable community-engaged strategies for reducing COVID-19 disparities by increasing SARS-CoV-2 test and vaccine access and uptake.

A Novel Physical Mechanism to Model Brownian Yet Non-Gaussian Diffusion: Theory and Application.

In the last years, a few experiments in the fields of biological and soft matter physics in colloidal suspensions have reported "normal diffusion" with a Laplacian probability distribution in the particle's displacements (i.e., Brownian yet non-Gaussian diffusion). To model this behavior, different stochastic and microscopic models have been proposed, with the former introducing new random elements that incorporate our lack of information about the media and the latter describing a limited number of interesting physical scenarios. This incentivizes the search of a more thorough understanding of how the media interacts with itself and with the particle being diffused in Brownian yet non-Gaussian diffusion. For this reason, a comprehensive mathematical model to explain Brownian yet non-Gaussian diffusion that includes weak molecular interactions is proposed in this paper. Based on the theory of interfaces by De Gennes and Langevin dynamics, it is shown that long-range interactions in a weakly interacting fluid at shorter time scales leads to a Laplacian probability distribution in the radial particle's displacements. Further, it is shown that a phase separation can explain a high diffusivity and causes this Laplacian distribution to evolve towards a Gaussian via a transition probability in the interval of time as it was observed in experiments. To verify these model predictions, the experimental data of the Brownian motion of colloidal beads on phospholipid bilayer by Wang et al. are used and compared with the results of the theory. This comparison suggests that the proposed model is able to explain qualitatively and quantitatively the Brownian yet non-Gaussian diffusion.

Neurogenetic traits outline vulnerability to cortical disruption in Parkinson's disease.

The genetic traits that underlie vulnerability to neuronal damage across specific brain circuits in Parkinson's disease (PD) remain to be elucidated. In this study, we characterized the brain topological intersection between propagating connectivity networks in controls and PD participants and gene expression patterns across the human cortex - such as the SNCA gene. We observed that brain connectivity originated from PD-related pathology epicenters in the brainstem recapitulated the anatomical distribution of alpha-synuclein histopathology in postmortem data. We also discovered that the gene set most related to cortical propagation patterns of PD-related pathology was primarily involved in microtubule cellular components. Thus, this study sheds light on new avenues for enhancing detection of PD neuronal vulnerability via an evaluation of in vivo connectivity trajectories across the human brain and successful integration of neuroimaging-genetic strategies.

Imaging Cognitive Impairment and Impulse Control Disorders in Parkinson's Disease.

Dementia and mild forms of cognitive impairment as well as neuropsychiatric symptoms (i. e., impulse control disorders) are frequent and disabling non-motor symptoms of Parkinson's disease (PD). The identification of changes in neuroimaging studies for the early diagnosis and monitoring of the cognitive and neuropsychiatric symptoms associated with Parkinson's disease, as well as their pathophysiological understanding, are critical for the development of an optimal therapeutic approach. In the current literature review, we present an update on the latest structural and functional neuroimaging findings, including high magnetic field resonance and radionuclide imaging, assessing cognitive dysfunction and impulse control disorders in PD.

Serial DaT-SPECT imaging in asymptomatic carriers of LRRK2 G2019S mutation: 8 years' follow-up.

BACKGROUND: Carriers of the G2019S mutation of LRRK2 provide a great opportunity to investigate the premotor stages of Parkinson's disease (PD). We have studied by serial clinical and dopamine transporter single photon emission computed tomography (DaT-SPECT) evaluations a cohort of asymptomatic carriers of the LRRK2-G2019S mutation in order to evaluate the usefulness of these tools as biomarkers. Here we report the results of the extended follow-up of this cohort at 8 years. METHODS: Seventeen participants, of the 25 available from the 4-year evaluation, completed the 8-year assessment. UPDRS-III, UPSIT test and DaT-SPECT imaging (123 I-ioflupane) were performed. We used repeated-measures linear mixed effects models to examine the changes in DaT binding over time. RESULTS: Three carriers had converted to PD at 4 years. One additional carrier converted at 8 years. PD-converters had lower striatal DaT binding at baseline than non-converters. There was a significant decline of DaT binding over time, with a mean annual rate of 3.5%, with somewhat inter-individual and intra-individual variability and comparable between PD-converters and non-converters. No carrier with DAT binding ratio above an undefined threshold between 0.5 and 0.8 developed PD symptoms. The age-adjusted UPSIT score did not change significantly over time. CONCLUSIONS: The rate of conversion to PD at 8 years in this cohort aged ~58 years at baseline was 16%. The observed decline of DaT binding over time and its association with the phenotype render DaT-SPECT a potentially useful tool for monitoring the premotor stage of the disease, although at the individual level its ability to predict phenoconversion is limited.

Three novel quantum-inspired swarm optimization algorithms using different bounded potential fields.

Based on the behavior of the quantum particles, it is possible to formulate mathematical expressions to develop metaheuristic search optimization algorithms. This paper presents three novel quantum-inspired algorithms, which scenario is a particle swarm that is excited by a Lorentz, Rosen-Morse, and Coulomb-like square root potential fields, respectively. To show the computational efficacy of the proposed optimization techniques, the paper presents a comparative study with the classical particle swarm optimization (PSO), genetic algorithm (GA), and firefly algorithm (FFA). The algorithms are used to solve 24 benchmark functions that are categorized by unimodal, multimodal, and fixed-dimension multimodal. As a finding, the algorithm inspired in the Lorentz potential field presents the most balanced computational performance in terms of exploitation (accuracy and precision), exploration (convergence speed and acceleration), and simulation time compared to the algorithms previously mentioned. A deeper analysis reveals that a strong potential field inside a well with weak asymptotic behavior leads to better exploitation and exploration attributes for unimodal, multimodal, and fixed-multimodal functions.

Eficacia de la cánula nasal de alto flujo en patologías respiratorias / Efficiency of high flow nasal cannula in pediatric respiratory pathologies

Introducción: En la edad pediátrica hay factores predisponentes importantes que hacen a los niños ser más vulnerables a presentar insuficiencia respiratoria aguda (IRA). Objetivo: Demostrar los beneficios del uso de la cánula nasal de alto flujo (CNAF) en pacientes menores de 5 años con IRA secundaria a enfermedades respiratorias y admitidos a la unidad de cuidados intensivos pediátricos (UCIP). Sujetos y Métodos: Estudio analítico observacional de cohortes mixtas, donde una cohorte esta formada por un grupo expuesto a la CNAF evaluada de manera prospectiva, mientras se comparo con una cohorte histórica. Resultados: 138 pacientes fueron admitidos al estudio de los cuales 69 fueron casos manejados con CNAF y 69 fueron controles que no estuvieron expuestos al uso de la CNAF pero sí a otros modos de ventilación mecánica invasiva. Los días de oxigenoterapia fueron estadísticamente menores en el grupo de casos de 13 (DE 8.01) días a 22 (DE 20.7) días en el grupo control (P = <0.05). Al igual los días de UCIP y los días totales de hospitalización fueron menores en el grupo manejado con CNAF (P = 0.011 y P = 0.001, respectivamente), con una media de tiempo de 10 (DE 7.8) días en UCIP y 17 (DE 9.25) días intrahospitalarios para el grupo de casos versus 14 (DE 10.1) días en UCIP y 28 (DE 23.9) días intrahospitalarios para el grupo control. Conclusión: La CNAF es un método de soporte respiratorio no invasivo, efectivo y fácil de usar en la población pediátrica con IRA secundario a diversas patologías respiratorias.

Introduction: During pediatric ages there are important predisposing factors that make children more vulnerable to present acute respiratory failure (ARF). Objective: Determine the benefits of the use of high flow nasal cannula (HFNC) in patients younger than 5 years with ARF, secondary to respiratory diseases and admitted to the pediatric intensive care unit (PICU). Subjects and Method: Analytical observational study of mixed type cohorts, where a cohort is formed by the group exposed to HFNC and evaluated prospectively, while it was compared with a historical cohort. Results: 138 patients were admitted to the study of which 69 were cases handled with HFNC and 69 were controls who were not exposed to the use of HFNC but to other types of invasive mechanical ventilation. Oxygen therapy days were statistically shorter in the case group from 13 (SD 8.01) days to 22 (SD 20.7) days in the control group (P = <0.05). The length of stay in PICU and the total inpatient days were lower in the group managed with HFNC (P = 0.011, P = 0.001), with a mean time of 10 (SD 7.8) days in PICU and 17 (SD 9.25) inpatient days for the case group versus 14 (SD 10.1) days in PICU and 28 (SD 23.9) inpatient days for the control group. Conclusion: HFNC system is a non-invasive respiratory support method, simple, effective and easy to use in the pediatric population less than 5 years of age with ARF due to various respiratory diseases.