Acute myocarditis associated with anti-COVID-19 vaccination.

Novel anti-coronavirus disease 2019 mRNA vaccines are rapidly implemented worldwide. Therefore, attention should be given to potentially life-threatening adverse reactions. We report on three young male patients, who developed acute myocarditis 2 days after receiving the second dose of the BNT162b2 vaccine. Primary acute myocarditis was not previously reported in association with vaccines that do not include adjuvants. A high index of suspicion should be maintained in order to diagnose and treat patients who develop auto-inflammatory vaccine-related complications in a timely manner. Further research is required in order to explore the significance of this phenomenon and its underlying molecular mechanism.

[HILLEL YAFFE MEDICAL CENTER - SIXTY YEARS OF ADVANCEMENT].

INTRODUCTION: The Hillel Yaffe Medical Center began its journey sixty years ago. Since its early days, the hospital's dedicated teams have struggled to bridge the gaps between limited resources and their uncompromising desire to meet patients' needs. Today, Hillel Yaffe Medical Center possesses more than five hundred beds in approximately eighty departments and units and dozens of ambulatory clinics. The Medical Center serves a population of half a million residents, with forecasts pointing to unprecedented growth, due to vast construction in the area and the settlement of the new city of Harish. In addition to the devoted care of patients, the other pillars of excellence in medicine, namely research and teaching, are actively developing. Hillel Yaffe is affiliated with the Technion - Israel Institute of Technology, and many of its physicians have academic appointments, owing to their dedication to scientific research and academic teaching, in addition to excellence in clinical practice. Research laboratories located in the medical center are operated by physicians and scientists, enabling them to conduct studies in basic science. Academic teaching and research are also practiced by nurses and other practitioners. The Hillel-Yaffe School of Nursing, affiliated with Tel Aviv University, has recently won the Ministry of Health Star Program for its high achievements. This issue is dedicated to articles written by Hillel Yaffe Medical Center's physicians in a variety of fields.

[Telemedicine: a novel service in pediatric emergency care].

INTRODUCTION: Telemedicine is a field that deals with monitoring and caring for patients who are physically apart from the caregivers, so they cannot communicate without technological means. The use of telemedicine has been recognized by a number of official organizations worldwide. This article reviews a unique service, "pediatrician online", provided by Clalit HMO, through Medtrix Ltd, with Schneider Children's Hospital specialists' supervision. With this service, parents can receive medical consultation from pediatricians beyond community clinic hours. The service is provided by telephone, computer or a mobile application, and when possible video calls are made. AIMS: To describe and analyze four years of telemedicine experience of the "pediatrician online" service. METHODS: A retrospective study was performed including analysis of all consultation calls conducted between November 2009 (the beginning of the project) and December 2013. Every call to the service was recorded and documented. Furthermore, analysis was conducted of follow-up calls to 4% of the applicants in order to monitor medical outcome and satisfaction. RESULTS: During the first four years approximately half a million consultation calls were provided. The average time from referral to obtaining medical advice was eight minutes. The duration of the consultation was four and a half minutes on average. Most of the calls were related to young children under 4 years (74%), dealing with common pediatric problems - fever (23%), respiratory complaints (17%), and gastrointestinal problems (12%). One-third of the applicants intended to go to the emergency department before they called the service, but only about one-sixth were referred at the end of the consultation. Among those referred, only about 60% actually went to the emergency department. The use of video-calls has been increasing, and reached an average of 30% of the applications. Satisfaction with the service was very high according to surveys, scoring 9.8 out of ten. Eighty-two percent of patients sampled reported medical improvement on the next day. CONCLUSIONS: There is a very high demand for consulting pediatricians beyond clinic hours. The use of telemedicine, as provided by the "pediatrician online" service, addresses this need safely and effectively with high patient satisfaction. Discussion: The use of telemedicine is expected to expand. In order to ensure its proper use while recognizing the capabilities and limitations, controlled studies should be conducted, exploring the outcome of different approaches in various situations.

Extracorporeal Membrane Oxygenation as a Resuscitation Measure in the Pediatric Emergency Department.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) may serve as a bridge to regain cardiac function in refractory resuscitation. However, its use has so far been limited owing to low availability, especially in emergency departments. OBJECTIVES: To describe two children with acute myocarditis successfully treated with ECMO in the emergency department of a tertiary pediatric medical center. DESCRIPTION: The children presented with vomiting, followed by rapid deterioration to cardiogenic shock that failed to respond to conservative treatment. Given the urgency of their condition and its presumably reversible (viral) etiology, treatment with ECMO was initiated in the department's resuscitation room. RESULTS: Outcome was excellent, and cardiac function remained normal throughout 6 and 10 months follow-up. CONCLUSIONS: Extracorporeal life support has enormous potential in the emergency department and warrants further assessment.

C-Reactive protein levels in children with primary herpetic gingivostomatitis.

BACKGROUND: C-reactive protein (CRP) is often used to distinguish bacterial from viral infections. However, the CRP level does have implications, which depend on the clinical scenario and are still under research. OBJECTIVES: To evaluate the distribution of CRP levels in children with primary herpetic gingivostomatitis. METHODS: The electronic database of a tertiary pediatric medical center was searched for all inpatients with a diagnosis of primary herpetic gingivostomatitis without bacterial coinfection. Background and clinical information was collected and CRP levels were analyzed. RESULTS: The study group consisted of 66 patients aged 8 months to 7.1 years who met the study criteria. The average CRP was 7.4 mg/dl (normal 0.5 mg/dl). More than a third of the patients had a level higher than 7 mg/dl. CONCLUSIONS: High values of CRP are prevalent in patients with primary herpetic gingivostomatitis, similar to adenoviral infections and some bacterial infections.

Community-associated methicillin-resistant Staphylococcus aureus infections in Israel.

BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus infections are increasingly being documented worldwide. In Israel, however, CA-MRSA infections have not yet been reported, so awareness among physicians may be low. OBJECTIVE: To alert physicians to the possibility of CA-MRSA infection, which necessitates a distinct therapeutic approach. METHODS: We present three children with soft tissue infections caused by CA-MRSA who were treated in our medical center from January to March 2009. RESULTS: In all three cases CA-MRSA was identified as the causative pathogen after surgical or spontaneous drainage. On susceptibility testing, the organisms were resistant to beta-lactam antibiotics but susceptible to clindamycin, rifampicin and trimethoprim-sulfamethoxazole. CONCLUSIONS: Physicians should maintain an index of suspicion for CA-MRSA infections. The antibiotic-resistance profile of S. aureus should be watched carefully, and in particular, cultures should be obtained whenever soft tissue infections fail to respond to conventional treatment.

Encoding by response duration in the basal ganglia.

Several models have suggested that information transmission in the basal ganglia (BG) involves gating mechanisms, where neuronal activity modulates the extent of gate aperture and its duration. Here, we demonstrate that BG response duration is informative about a highly abstract stimulus feature and show that the duration of "gate opening" can indeed be used for information transmission through the BG. We analyzed recordings from three BG locations: the external part of the globus pallidus (GPe), the substantia nigra pars reticulata (SNr), and dopaminergic neurons from the substantia nigra pars compacta (SNc) during performance of a probabilistic visuomotor task. Most (>85%) of the neurons showed significant rate modulation following the appearance of cues predicting future reward. Trial-to-trial mutual information analysis revealed that response duration encoded reward prospects in many (42%) of the responsive SNr neurons, as well as in the SNc (26.9%), and the GPe (29.3%). Whereas the low-frequency discharge SNc neurons responded with only an increase in firing rate, SNr and GPe neurons with high-frequency tonic discharge responded with both increases and decreases. Conversely, many duration-informative neurons in SNr (68%) and GPe (50%) responded with a decreased rather than an increased rate. The response duration was more informative than the extreme (minimal or maximal) amplitude or spike count in responsive bins of duration-informative neurons. Thus response duration is not simply correlated with the discharge rate and can provide additional information to the target structures of the BG.

Lack of spike-count and spike-time correlations in the substantia nigra reticulata despite overlap of neural responses.

Previous studies of single neurons in the substantia nigra reticulata (SNr) have shown that many of them respond to similar events. These results, as well as anatomical studies, suggest that SNr neurons share inputs and thus may have correlated activity. Different types of correlation can exist between pairs of neurons. These are traditionally classified as either spike-count ("signal" and "noise") or spike-timing (spike-to-spike and joint peristimulus time histograms) correlations. These measures of neuronal correlation are partially independent and have different implications. Our purpose was to probe the computational characteristics of the basal ganglia output nuclei through an analysis of these different types of correlation in the SNr. We carried out simultaneous multiple-electrode single-unit recordings in the SNr of two monkeys performing a probabilistic delayed visuomotor response task. A total of 113 neurons (yielding 355 simultaneously recorded pairs) were studied. Most SNr neurons responded to one or more task-related events, with instruction cue (69%) and reward (63%) predominating. Response-match analysis, comparing peristimulus time histograms, revealed a significant overlap between response vectors. However, no measure of average correlation differed significantly from zero. The lack of significant SNr spike-count population correlations appears to be an exceptional phenomenon in the brain, perhaps indicating unique event-related processing by basal ganglia output neurons to achieve better information transfer. The lack of spike-timing correlations suggests that the basal high-frequency discharge of SNr neurons is not driven by the common inputs and is probably intrinsic.

Physiology and pathophysiology of the basal ganglia-thalamo-cortical networks.

Low-frequency resting tremor is one of the cardinal signs of Parkinson's disease (PD) and occurs also in some of its animal models. Current physiological studies and models of the basal ganglia indicate that changes of discharge pattern and synchronization of basal ganglia neurons rather than modification in their discharge rate are crucial to the pathophysiology of PD. However, parkinsonian tremor is not strictly correlated with the synchronous oscillations in the basal ganglia networks. We therefore suggest that abnormal basal ganglia output enforces abnormal thalamo-cortical processing leading to akinesia, the main negative symptom of Parkinson's disease. The parkinsonian positive motor signs, such as tremor and rigidity, most likely evolve as a downstream compensatory mechanism.

Midbrain dopamine neurons encode decisions for future action.

Current models of the basal ganglia and dopamine neurons emphasize their role in reinforcement learning. However, the role of dopamine neurons in decision making is still unclear. We recorded from dopamine neurons in monkeys engaged in two types of trial: reference trials in an instructed-choice task and decision trials in a two-armed bandit decision task. We show that the activity of dopamine neurons in the decision setting is modulated according to the value of the upcoming action. Moreover, analysis of the probability matching strategy in the decision trials revealed that the dopamine population activity and not the reward during reference trials determines choice behavior. Because dopamine neurons do not have spatial or motor properties, we conclude that immediate decisions are likely to be generated elsewhere and conveyed to the dopamine neurons, which play a role in shaping long-term decision policy through dynamic modulation of the efficacy of basal ganglia synapses.

Physiological studies of information processing in the normal and Parkinsonian basal ganglia: pallidal activity in Go/No-Go task and following MPTP treatment.

Understanding the role of the basal ganglia in day to day behavior is critical for a better understanding of the role of these structures in pathological states--such as Parkinson's disease. To elucidate this connection, we studied pallidal activity in a monkey performing a delayed release Go/No-Go task and in monkeys treated with the dopaminergic neurotoxin--MPTP. We compared the results with the predictions of the action selection and reinforcement driven dimensionality reduction models of the basal ganglia. The fraction of responding pallidal neurons, as well as the ratio of positive to negative responses, were equal in the Go and the No-Go modes. The fraction of pallidal neurons with significant responses following the trigger signal (19/26) was higher than that following the visual cue (11/26); however, the fraction of negative responses was significantly higher following the cue signal (47%) than that following the trigger signal (22%). Most (80%) of the cue responses were sensitive to the laterality of the cue, whereas only 25% of the responses following the trigger signal were sensitive to the cue or movement direction. Finally, pallidal spiking activity was not correlated in the normal behaving monkey, and became highly synchronized following MPTP treatment. We conclude that pallidal activity in the normal monkey is consistent with the model of action selection, assuming that action is selected following the visual cue. However, the reinforcement driven dimensionality reduction model is consistent with both the Go/No-Go responses and the normal/MPTP correlation studies.

Coincident but distinct messages of midbrain dopamine and striatal tonically active neurons.

Midbrain dopamine and striatal tonically active neurons (TANs, presumed acetylcholine interneurons) signal behavioral significance of environmental events. Since striatal dopamine and acetylcholine affect plasticity of cortico-striatal transmission and are both crucial to learning, they may serve as teachers in the basal ganglia circuits. We recorded from both neuronal populations in monkeys performing a probabilistic instrumental conditioning task. Both neuronal types respond robustly to reward-related events. Although different events yielded responses with different latencies, the responses of the two populations coincided, indicating integration at the target level. Yet, while the dopamine neurons' response reflects mismatch between expectation and outcome in the positive domain, the TANs are invariant to reward predictability. Finally, TAN pairs are synchronized, compared to a minority of dopamine neuron pairs. We conclude that the striatal cholinergic and dopaminergic systems carry distinct messages by different means, which can be integrated differently to shape the basal ganglia responses to reward-related events.

Discharge rate of substantia nigra pars reticulata neurons is reduced in non-parkinsonian monkeys with apomorphine-induced orofacial dyskinesia.

Involuntary movements (dyskinesia) are a common symptom of dopamine-replacement therapy in parkinsonian patients, neuroleptic drug treatment of mental patients, and tic disorders. Levodopa-induced dyskinesia has been shown to be associated with substantial reduction of firing rate in the internal part of the globus pallidus. This study characterizes the changes that occur in the activity of the substantia nigra pars reticulata (SNr) of non-parkinsonian (normal) monkeys with apomorphine (APO)-induced orofacial dyskinesia. We conducted extracellular recordings of SNr neurons of two monkeys before and after induction of orofacial dyskinesia by systemic administration of APO. Involuntary orofacial movements appeared a few minutes after the injections and lasted 20-40 min. Almost all recorded neurons changed their firing rate after APO injection (96%), and most declined (70%). The mean amplitude of decreases was also larger than that of increases (40 vs. 21% of the control rate). Changes in firing pattern were not significant on average. Pairs of SNr neurons were uncorrelated before APO injection, similar to the normal pallidum. However, unlike the increased correlations in the pallidum that accompany parkinsonism, orofacilal dyskinesia in non-parkinsonian monkeys was not associated with changes in correlation between SNr neurons. We conclude that normal monkeys treated with APO can model orofacial dyskinesia and tic disorders that are a consequence of dopaminergic over-activity. These symptoms appear to be more related to reduced firing rate of SNr neurons and thus to disinhibition of their targets, than to changes in pattern and synchronization.

Anatomical funneling, sparse connectivity and redundancy reduction in the neural networks of the basal ganglia.

The major anatomical characteristics of the main axis of the basal ganglia are: (1) Numerical reduction in the number of neurons across layers of the feed-forward network, (2) lateral inhibitory connections within the layers, and (3) neuro-modulatory effects of dopamine and acetylcholine, both on the basal ganglia neurons and on the efficacy of information transmission along the basal ganglia axis. We recorded the simultaneous activity of neurons in the output stages of the basal ganglia as well as the activity of dopaminergic and cholinergic neurons during the performance of a probability decision-making task. We found that the functional messages of the cholinergic and dopaminergic neurons differ, and that the cholinergic message is less specific than that of the dopaminergic neurons. The output stage of the basal ganglia showed uncorrelated neuronal activity. We conclude that despite the huge numerical reduction from the cortex to the output nuclei of the basal ganglia, the activity of these nuclei represents an optimally compressed (uncorrelated) version of distinctive features of cortical information.