The Frequency and Clinical Impact of Synonymous HTT Loss-of-Interruption and Duplication-of-interruption Variants in a Diverse HD Cohort.

PURPOSE: To determine the frequency and clinical impact of loss-of-interruption (LOI) and duplication-of-interruption (DOI) modifier variants of the HTT CAG and CCG repeat in a cohort of individuals with Huntington disease (HD). METHODS: We screened symptomatic HD participants from the UBC HD Biobank and five research sites for sequence variants. Following variant identification, we examined the clinical impact and frequency in the reduced penetrance range. RESULTS: Participants with CAG-CCG LOI and CCG LOI variants have a similar magnitude of earlier onset of HD, by 12.5 years. The sequence variants exhibit ancestry-specific differences. Participants with the CAG-CCG LOI variant also have a faster progression of TMS by 1.9 units per year. Symptomatic participants with the CAG-CCG LOI variant show enrichment in the reduced penetrance range. The CAG-CCG LOI variant explains the onset of two symptomatic HD participants with diagnostic repeats below the pathogenetic range. CONCLUSION: Our findings have significant clinical implications for participants with the CAG-CCG LOI variant who receive inaccurate diagnoses near diagnostic cut-off ranges. Improved diagnostic testing approaches and clinical management are needed for these individuals. We present the largest and most diverse HTT CAG and CCG sequence variant cohort and emphasize their importance in clinical presentation in HD.

JYNNEOS Vaccination Coverage Among Persons at Risk for Mpox - United States, May 22, 2022-January 31, 2023.

From May 2022 through the end of January 2023, approximately 30,000 cases of monkeypox (mpox) have been reported in the United States and >86,000 cases reported internationally.* JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) is recommended for subcutaneous administration to persons at increased risk for mpox (1,2) and has been demonstrated to provide protection against infection (3-5). To increase the total number of vaccine doses available, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) on August 9, 2022, recommending administration of the vaccine intradermally (0.1 mL per dose) for persons aged ≥18 years who are recommended to receive it (6); intradermal administration can generate an equivalent immune response to that achieved through subcutaneous injection using approximately one fifth the subcutaneous dose (7). CDC analyzed JYNNEOS vaccine administration data submitted to CDC from jurisdictional immunization information systems (IIS)† to assess the impact of the EUA and to estimate vaccination coverage among the population at risk for mpox. During May 22, 2022-January 31, 2023, a total of 1,189,651 JYNNEOS doses (734,510 first doses and 452,884 second doses)§ were administered. Through the week of August 20, 2022, the predominant route of administration was subcutaneous, after which intradermal administration became predominant, in accordance with FDA guidance. As of January 31, 2023, 1-dose and 2-dose (full vaccination) coverage among persons at risk for mpox is estimated to have reached 36.7% and 22.7%, respectively. Despite a steady decline in mpox cases from a 7-day daily average of more than 400 cases on August 1, 2022, to five cases on January 31, 2023, vaccination for persons at risk for mpox continues to be recommended (1). Targeted outreach and continued access to and availability of mpox vaccines to persons at risk are important to help prevent and minimize the impact of a resurgence of mpox.

Molecular mechanisms, physiological roles, and therapeutic implications of ion fluxes in bone cells: Emphasis on the cation-Cl- cotransporters.

Bone turnover diseases are exceptionally prevalent in human and come with a high burden on physical health. While these diseases are associated with a variety of risk factors and causes, they are all characterized by common denominators, that is, abnormalities in the function or number of osteoblasts, osteoclasts, and/or osteocytes. As such, much effort has been deployed in the recent years to understand the signaling mechanisms of bone cell proliferation and differentiation with the objectives of exploiting the intermediates involved as therapeutic preys. Ion transport systems at the external and in the intracellular membranes of osteoblasts and osteoclasts also play an important role in bone turnover by coordinating the movement of Ca2+ , PO4 2- , and H+ ions in and out of the osseous matrix. Even if they sustain the terminal steps of osteoformation and osteoresorption, they have been the object of very little attention in the last several years. Members of the cation-Cl- cotransporter (CCC) family are among the systems at work as they are expressed in bone cells, are known to affect the activity of Ca2+ -, PO4 2- -, and H+ -dependent transport systems and have been linked to bone mass density variation in human. In this review, the roles played by the CCCs in bone remodeling will be discussed in light of recent developments and their potential relevance in the treatment of skeletal disorders.

Evaluation of five methods to identify composite restorations in human teeth on a forensic purpose-an ex vivo comparative study.

The use of tooth-colored composite resin materials in dentistry is increasing. As composite restorations appear similar to the natural tooth structure, their detection is becoming more challenging. The aim of this study was to compare five diagnostic methods for detection of dental restorations and to create reliable postmortem dental records for forensic purposes. A conventional examination method without a direct light source (CONV), with a dental loupe light (DL), Galilean loupes with a direct light source (GDL), a fluorescence-inducing device (FIT), and intraoral radiographs (RX) were compared. Dentists specializing in conservative dentistry or oral surgery and dentistry students participated. Regarding sensitivity, specificity, positive predictive value, and negative predictive value, FIT and RX showed significantly higher results than CONV, DL, and GDL. RX and FIT showed comparable results in identifying composite restorations but depending on their location. The combination of both methods may lead to even better results. In conclusion fluorescence-inducing devices show good results in identifying composite restorations and therefore should be considered as a standard tool in forensic examinations. Another advantage is their small size, low cost, and mobility. Good illumination and magnification devices are recommended to enhance performance during conventional examinations. Involving dentists specialized in conservative dentistry could contribute to dental identification.

Association of State-Issued Mask Mandates and Allowing On-Premises Restaurant Dining with County-Level COVID-19 Case and Death Growth Rates - United States, March 1-December 31, 2020.

CDC recommends a combination of evidence-based strategies to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 (1). Because the virus is transmitted predominantly by inhaling respiratory droplets from infected persons, universal mask use can help reduce transmission (1). Starting in April, 39 states and the District of Columbia (DC) issued mask mandates in 2020. Reducing person-to-person interactions by avoiding nonessential shared spaces, such as restaurants, where interactions are typically unmasked and physical distancing (≥6 ft) is difficult to maintain, can also decrease transmission (2). In March and April 2020, 49 states and DC prohibited any on-premises dining at restaurants, but by mid-June, all states and DC had lifted these restrictions. To examine the association of state-issued mask mandates and allowing on-premises restaurant dining with COVID-19 cases and deaths during March 1-December 31, 2020, county-level data on mask mandates and restaurant reopenings were compared with county-level changes in COVID-19 case and death growth rates relative to the mandate implementation and reopening dates. Mask mandates were associated with decreases in daily COVID-19 case and death growth rates 1-20, 21-40, 41-60, 61-80, and 81-100 days after implementation. Allowing any on-premises dining at restaurants was associated with increases in daily COVID-19 case growth rates 41-60, 61-80, and 81-100 days after reopening, and increases in daily COVID-19 death growth rates 61-80 and 81-100 days after reopening. Implementing mask mandates was associated with reduced SARS-CoV-2 transmission, whereas reopening restaurants for on-premises dining was associated with increased transmission. Policies that require universal mask use and restrict any on-premises restaurant dining are important components of a comprehensive strategy to reduce exposure to and transmission of SARS-CoV-2 (1). Such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States (3,4).

Counties with High COVID-19 Incidence and Relatively Large Racial and Ethnic Minority Populations - United States, April 1-December 22, 2020.

Long-standing systemic social, economic, and environmental inequities in the United States have put many communities of color (racial and ethnic minority groups) at increased risk for exposure to and infection with SARS-CoV-2, the virus that causes COVID-19, as well as more severe COVID-19-related outcomes (1-3). Because race and ethnicity are missing for a proportion of reported COVID-19 cases, counties with substantial missing information often are excluded from analyses of disparities (4). Thus, as a complement to these case-based analyses, population-based studies can help direct public health interventions. Using data from the 50 states and the District of Columbia (DC), CDC identified counties where five racial and ethnic minority groups (Hispanic or Latino [Hispanic], non-Hispanic Black or African American [Black], non-Hispanic Asian [Asian], non-Hispanic American Indian or Alaska Native [AI/AN], and non-Hispanic Native Hawaiian or other Pacific Islander [NH/PI]) might have experienced high COVID-19 impact during April 1-December 22, 2020. These counties had high 2-week COVID-19 incidences (>100 new cases per 100,000 persons in the total population) and percentages of persons in five racial and ethnic groups that were larger than the national percentages (denoted as "large"). During April 1-14, a total of 359 (11.4%) of 3,142 U.S. counties reported high COVID-19 incidence, including 28.7% of counties with large percentages of Asian persons and 27.9% of counties with large percentages of Black persons. During August 5-18, high COVID-19 incidence was reported by 2,034 (64.7%) counties, including 92.4% of counties with large percentages of Black persons and 74.5% of counties with large percentages of Hispanic persons. During December 9-22, high COVID-19 incidence was reported by 3,114 (99.1%) counties, including >95% of those with large percentages of persons in each of the five racial and ethnic minority groups. The findings of this population-based analysis complement those of case-based analyses. In jurisdictions with substantial missing race and ethnicity information, this method could be applied to smaller geographic areas, to identify communities of color that might be experiencing high potential COVID-19 impact. As areas with high rates of new infection change over time, public health efforts can be tailored to the needs of communities of color as the pandemic evolves and integrated with longer-term plans to improve health equity.

Clinical and Demographic Characteristics of Upper Limb Dystonia.

BACKGROUND: Knowledge of characteristics in upper limb dystonia remains limited, derived primarily from small, single-site studies. OBJECTIVE: The objective of this study was to characterize demographic and clinical characteristics of upper limb dystonia from the Dystonia Coalition data set, a large, international, multicenter resource. METHODS: We evaluated clinical and demographic characteristics of 367 participants with upper limb dystonia from onset, comparing across subcategories of focal (with and without dystonia spread) versus nonfocal onset. RESULTS: Focal onset occurred in 80%; 67% remained focal without spread. Task specificity was most frequent in this subgroup, most often writer's cramp and affecting the dominant limb (83%). Focal onset with spread was more frequent in young onset (<21 years). Focal onset occurred equally in women and men; nonfocal onset affected women disproportionately. CONCLUSIONS: Upper limb dystonia distribution, focality, and task specificity relate to onset age and likelihood of regional spread. Observations may inform clinical counseling and design, execution, and interpretation of future studies. © 2020 International Parkinson and Movement Disorder Society.

Finding Sarcocystis spp. on the Tioman Island: 28S rRNA gene next-generation sequencing reveals nine new Sarcocystis species.

The Tioman Island of Malaysia experienced acute muscular sarcocystosis outbreaks from 2011 to 2014. So far, a previous study based on the 18S rRNA gene sequencing has reported S. singaporensis, S. nesbitti and Sarcocystis sp. YLL-2013 in water samples acquired from the island, thus confirming the waterborne nature of this emerging parasitic disease. This study aimed to improve the detection methods for Sarcocystis, in order to have a clearer picture of the true diversity of Sarcocystis species in Tioman. A new primer set (28S R7F-28S R8 Deg R) was designed to amplify the 28S rRNA gene of Sarcocystis. Subsequently, Sarcocystidae was detected in 65.6% (21/32) of water samples and 28% (7/25) of soil samples acquired between 2014 and 2015 from Tioman. Next-generation sequencing (NGS) on 18 of the positive samples was then performed using amplicons generated from the same primer set. This yielded 53 potentially unique Sarcocystidae sequences (290 bp), of which nine of the most abundant, prevalent and unique sequences were named herein. In contrast, NGS of the 18S rRNA gene V9 hypervariable region of 10 selected samples detected only two Sarcocystis species (160 bp). S. mantioni was the most ubiquitous sequence found in this study.

Is There an Advantage to Minimizing Surgery in Scaphocephaly? A Study on Extended Strip Craniectomy Versus Extensive Cranial Vault Remodeling.

BACKGROUND: Different techniques have been described to correct scaphocephaly. In authors' institution, total cranial vault remodeling (TCVR) was the standard of care. To limit the extent of surgery and the need for transfusion, the technique was minimized to extended strip craniectomy (ESC) without helmet therapy. This retrospective study compares outcome and morbidity between ESC and TCVR. METHODS: Twenty-seven scaphocephalic patients were included. The ESC was performed in 9 patients between 2012 and 2014, and TCVR in 17 patients between 2008 and 2016. Data on blood loss and transfusion rate, duration of surgery, length of hospital stay (LOS), head circumference, and cephalic index (CI) were collected retrospectively. A cosmetic outcome score (COS) was developed to rate esthetic outcome since CI is a limited and crude measurement of cosmetic outcome. RESULTS: The LOS was identical in both groups, but duration of surgery was significantly shorter in ESC (P < 0.0001). Transfusion rate appeared higher in the TCVR group, but differences were not significant (P = 0.11). Cosmetic outcome appeared slightly worse in the ESC group, but results were not significantly different (P = 0.66). There was, however, a significant improvement in postoperative CI in the TCVR group (P < 0.0001). CONCLUSION: The only advantage of ESC was the reduced duration of surgery, but this could not prevent the need for transfusion in this group of patients. The improvement of the CI was significantly less pronounced after ESC, but the COS was not significantly worse in the ESC group. The scar and LOS were similar in both groups. Therefore, our findings indicate that minimizing TCVR to ESC without helmet therapy does not provide significant advantages.

Internal Carotid Artery Occlusion Causing Acute Cranial Neuropathies.

A 54-year-old male with a history of left posterior parietal ischemic stroke, epilepsy, tobacco and marijuana smoking, and alcohol abuse, presented with acute left visual loss and diplopia. On examination, he had reduced left visual acuity and a left oculomotor nerve palsy. CT angiogram from aortic arch to circle of Willis identified extensive thrombus occluding the left common and internal carotid arteries, extending to the left ophthalmic artery. This case demonstrates acute visual loss from ophthalmic artery occlusion, and left oculomotor nerve palsy from occlusion of the inferolateral trunk of the internal carotid artery (cavernous sinus portion).

Phenotypic insights into ADCY5-associated disease.

BACKGROUND: Adenylyl cyclase 5 (ADCY5) mutations is associated with heterogenous syndromes: familial dyskinesia and facial myokymia; paroxysmal chorea and dystonia; autosomal-dominant chorea and dystonia; and benign hereditary chorea. We provide detailed clinical data on 7 patients from six new kindreds with mutations in the ADCY5 gene, in order to expand and define the phenotypic spectrum of ADCY5 mutations. METHODS: In 5 of the 7 patients, followed over a period of 9 to 32 years, ADCY5 was sequenced by Sanger sequencing. The other 2 unrelated patients participated in studies for undiagnosed pediatric hyperkinetic movement disorders and underwent whole-exome sequencing. RESULTS: Five patients had the previously reported p.R418W ADCY5 mutation; we also identified two novel mutations at p.R418G and p.R418Q. All patients presented with motor milestone delay, infantile-onset action-induced generalized choreoathetosis, dystonia, or myoclonus, with episodic exacerbations during drowsiness being a characteristic feature. Axial hypotonia, impaired upward saccades, and intellectual disability were variable features. The p.R418G and p.R418Q mutation patients had a milder phenotype. Six of seven patients had mild functional gain with clonazepam or clobazam. One patient had bilateral globus pallidal DBS at the age of 33 with marked reduction in dyskinesia, which resulted in mild functional improvement. CONCLUSION: We further delineate the clinical features of ADCY5 gene mutations and illustrate its wide phenotypic expression. We describe mild improvement after treatment with clonazepam, clobazam, and bilateral pallidal DBS. ADCY5-associated dyskinesia may be under-recognized, and its diagnosis has important prognostic, genetic, and therapeutic implications. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Rapid stimulus-evoked astrocyte Ca2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo.

Increased neuron and astrocyte activity triggers increased brain blood flow, but controversy exists over whether stimulation-induced changes in astrocyte activity are rapid and widespread enough to contribute to brain blood flow control. Here, we provide evidence for stimulus-evoked Ca(2+) elevations with rapid onset and short duration in a large proportion of cortical astrocytes in the adult mouse somatosensory cortex. Our improved detection of the fast Ca(2+) signals is due to a signal-enhancing analysis of the Ca(2+) activity. The rapid stimulation-evoked Ca(2+) increases identified in astrocyte somas, processes, and end-feet preceded local vasodilatation. Fast Ca(2+) responses in both neurons and astrocytes correlated with synaptic activity, but only the astrocytic responses correlated with the hemodynamic shifts. These data establish that a large proportion of cortical astrocytes have brief Ca(2+) responses with a rapid onset in vivo, fast enough to initiate hemodynamic responses or influence synaptic activity.

Next-generation sequencing identifies altered whole blood microRNAs in neuromyelitis optica spectrum disorder which may permit discrimination from multiple sclerosis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) have a similar clinical phenotype but represent distinct diseases, requiring different therapies. MicroRNAs (miRNAs) are short non-coding RNAs whose expression profiles can serve as diagnostic biomarkers and which may be involved in the pathophysiology of neuroinflammatory diseases. Here, we analyzed miRNA profiles in serum and whole blood of patients with NMOSD and clinically isolated syndrome (CIS)/relapsing-remitting MS (RRMS) as well as healthy controls by next-generation sequencing (NGS). METHODS: MiRNA expression profiles were determined by NGS in sera of patients with aquaporin-4 antibody-positive NMOSD (n = 20), CIS/RRMS (n = 20), and healthy controls (n = 20) and in whole blood of patients with NMOSD (n = 11), CIS/RRMS (n = 60), and healthy controls (n = 43). Differentially expressed miRNAs were calculated by analysis of variance and t tests. All significance values were corrected for multiple testing. Selected miRNAs were validated in whole blood of patients with NMOSD (n = 18) and CIS/RRMS (n = 19) by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: None of 261 miRNAs detected in serum but 178 of 416 miRNAs detected in whole blood showed significantly different expression levels among the three groups. Pairwise comparisons revealed 115 (NMOSD vs. CIS/RRMS), 141 (NMOSD vs. healthy controls), and 44 (CIS/RRMS vs. healthy controls) miRNAs in whole blood with significantly different expression levels. qRT-PCR confirmed different expression levels in whole blood of patients with NMOSD and CIS/RRMS for 9 out of 10 exemplarily chosen miRNAs. In silico enrichment analysis demonstrated an accumulation of altered miRNAs in NMOSD in particular in CD15(+) cells (i.e., neutrophils and eosinophils). CONCLUSIONS: This study identifies a set of miRNAs in whole blood, which may have the potential to discriminate NMOSD from CIS/RRMS and healthy controls. In contrast, miRNA profiles in serum do not appear to be promising diagnostic biomarkers for NMOSD. Enrichment of altered miRNAs in CD15(+) neutrophils and eosinophils, which were previously implicated in the pathophysiology of NMOSD, suggests that miRNAs could be involved in the regulation of these cells in NMOSD.

Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation.

The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b(+) cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an "oxidative stress memory" both in the periphery and CNS compartments, in chronic neuroinflammation.

Review of the performance of quantitative sensory testing methods to detect hyperalgesia in chronic pain patients on long-term opioids.

BACKGROUND: Opioid-induced hyperalgesia is a clinical syndrome whereby patients on long-term opioids become more sensitive to pain while taking opioids. Opioid-induced hyperalgesia is characterized by increased pain intensity over time, spreading of pain to other locations, and increased pain sensation to external stimuli. To characterize opioid-induced hyperalgesia, laboratory methods to measure hyperalgesia have been developed. To determine the performance of these methods, the authors conducted a systematic review of clinical studies that incorporate measures of hyperalgesia in chronic pain patients on long-term opioids. METHODS: PubMed and Cochrane databases were searched (terms: opioid induced hyperalgesia, study or trial, and long-term or chronic). Studies published in English were selected if they were conducted in chronic pain patients on long-term opioids and incorporated measures of hyperalgesia; acute/single-dose studies and/or conducted in healthy volunteers were excluded. RESULTS: Fourteen articles made the final selection (11 were selected from the search and 3 others were found from additional sources); there was one randomized controlled trial, one prospective controlled study, three prospective uncontrolled studies, and nine cross-sectional observation studies. Hyperalgesia measurement paradigms used included cold pain, heat pain, pressure pain, electrical pain, ischemic pain, and injection pain. Although none of the stimuli were capable of detecting patients' hyperalgesia, heat pain sensitivity showed some promising results. CONCLUSIONS: None of the measures reviewed herein met the criteria of a definitive standard for the measurement of hyperalgesia. Additional studies that use improved study design should be conducted.

Are there roles for brain cell senescence in aging and neurodegenerative disorders?

The term cellular senescence was introduced more than five decades ago to describe the state of growth arrest observed in aging cells. Since this initial discovery, the phenotypes associated with cellular senescence have expanded beyond growth arrest to include alterations in cellular metabolism, secreted cytokines, epigenetic regulation and protein expression. Recently, senescence has been shown to play an important role in vivo not only in relation to aging, but also during embryonic development. Thus, cellular senescence serves different purposes and comprises a wide range of distinct phenotypes across multiple cell types. Whether all cell types, including post-mitotic neurons, are capable of entering into a senescent state remains unclear. In this review we examine recent data that suggest that cellular senescence plays a role in brain aging and, notably, may not be limited to glia but also neurons. We suggest that there is a high level of similarity between some of the pathological changes that occur in the brain in Alzheimer's and Parkinson's diseases and those phenotypes observed in cellular senescence, leading us to propose that neurons and glia can exhibit hallmarks of senescence previously documented in peripheral tissues.

Genome sequencing reanalysis increases the diagnostic yield in dystonia.

PURPOSE: We investigated the contribution of genomic data reanalysis to the diagnostic yield of dystonia patients who remained undiagnosed after prior genome sequencing. METHODS: Probands with heterogeneous dystonia phenotypes who underwent initial genome sequencing (GS) analysis in 2019 were included in the reanalysis, which was performed through gene-specific discovery collaborations and systematic genomic data reanalysis. RESULTS: Initial GS analysis in 2019 (n = 111) identified a molecular diagnosis in 11.7 % (13/111) of cases. Reanalysis between 2020 and 2023 increased the diagnostic yield by 7.2 % (8/111); 3.6 % (4/111) through focused gene-specific clinical correlation collaborative efforts [VPS16 (two probands), AOPEP and POLG], and 3.6 % (4/111) by systematic reanalysis completed in 2023 [NUS1 (two probands) and DDX3X variants, and a microdeletion encompassing VPS16]. Seven of these patients had a high phenotype-based dystonia score ≥3. Notable unverified findings in four additional cases included suspicious variants of uncertain significance in FBXL4 and EIF2AK2, and potential phenotypic expansion associated with SLC2A1 and TREX1 variants. CONCLUSION: GS data reanalysis increased the diagnostic yield from 11.7 % to 18.9 %, with potential extension up to 22.5 %. While optimal timing for diagnostic reanalysis remains to be determined, this study demonstrates that periodic re-interrogation of dystonia GS datasets can provide additional genetic diagnoses, which may have significant implications for patients and their families.

Motor and Sensory Dysfunction in Musician's Dystonia.

Musicians' dystonia is a task-specific and painless loss of motor control in a previously well-executed task. It is increasingly recognized in the medical and musical community. Recent advances in neuroimaging, transcranial magnetic stimulation and novel techniques in electroencephalography have shed light on its underlying pathophysiology. To date, a deranged cortical plasticity leading to abnormal sensorimotor integration, combined with reduced inhibition across several levels of the motor pathway are likely mechanisms.This paper reviews the various phenomenology of musician's dystonia across keyboard, string, brass, flute and drum players. Treatment is often challenging. Medical therapies like botulinum toxin injection and rehabilitation method with sensorimotor training offer symptomatic relief and return to baseline performance to some musicians.

Super-spreaders of novel coronaviruses that cause SARS, MERS and COVID-19: a systematic review.

PURPOSE: Most index cases with novel coronavirus infections transmit disease to just one or two other individuals, but some individuals "super-spread"-they infect many secondary cases. Understanding common factors that super-spreaders may share could inform outbreak models, and be used to guide contact tracing during outbreaks. METHODS: We searched in MEDLINE, Scopus, and preprints to identify studies about people documented as transmitting pathogens that cause SARS, MERS, or COVID-19 to at least nine other people. We extracted data to describe them by age, sex, location, occupation, activities, symptom severity, any underlying conditions, disease outcome and undertook quality assessment for outbreaks published by June 2021. RESULTS: The most typical super-spreader was a male age 40+. Most SARS or MERS super-spreaders were very symptomatic, the super-spreading occurred in hospital settings and frequently the individual died. In contrast, COVID-19 super-spreaders often had very mild disease and most COVID-19 super-spreading happened in community settings. CONCLUSIONS: SARS and MERS super-spreaders were often symptomatic, middle- or older-age adults who had a high mortality rate. In contrast, COVID-19 super-spreaders tended to have mild disease and were any adult age. More outbreak reports should be published with anonymized but useful demographic information to improve understanding of super-spreading, super-spreaders, and the settings in which super-spreading happens.