The Vocal Flutter of Multiple System Atrophy: A Parkinsonian-Type Phenomenon?

BACKGROUND: Early features of multiple system atrophy (MSA) are similar to those in Parkinson's disease (PD), which can challenge differential diagnosis. Identifying clinical markers that help distinguish MSA from forms of parkinsonism is essential to promptly implement the most appropriate management plan. In the context of a thorough neurological evaluation, the presence of a vocal flutter might be considered a potential feature of MSA-parkinsonian type (MSA-P). CASES: This case series describes clinical histories of 3 individuals with MSA-P. In each case, vocal flutter was detected during neurological and motor speech evaluations. It seemed to be a concomitant feature with the constellation of other signs and symptoms that led to the clinical diagnosis. LITERATURE REVIEW: The vocal flutter may be described as pitch and loudness fluctuations during phonation. Different from a vocal tremor, the flutter phenomenon has higher oscillation frequencies. The neuropathological underpinnings of vocal flutter may be related to generalized laryngeal dysfunction that is commonly described in MSA-P. CONCLUSION: Vocal flutter may be a unique speech feature in some individuals who have MSA-P. Future studies using perceptual and acoustic measures of speech are warranted to quantify these observations and directly compare to other MSA variants, PD, and a control group.

A neonatal piglet model reveals interactions between nasal microbiota and influenza A virus pathogenesis.

While vaccination and therapeutics for prevention/treatment of influenza are available, new strategies are needed to combat influenza disease in susceptible populations, particularly young children and newborns. Host associated microbiota play an important role in modulating the virulence of numerous pathogens, including the influenza A virus. In this study, we examined microbiome-influenza interactions in a neonatal piglet model system. The nasal microbiome of newborn piglets was longitudinally sampled before and after intranasal infection with recombinant viruses expressing hemagglutinins (HAs) derived from distinct zoonotic H1 subtypes. We found that viruses expressing different parental HAs manifested unique patterns of pathogenicity, and varied impacts on microbial community diversity. Despite these virus specific differences, a consistent microbial signature of viral infection was detected. Our results indicate that influenza A virus infection associates with the restructuring of nasal microbiome and such shifts in microbial diversity may contribute to outcomes of viral infection in neonatal piglets.

Impacts of Deep Brain Stimulation of the Globus Pallidus Internus on Swallowing: A Retrospective, Cross-Sectional Study.

Deep brain stimulation (DBS) is a common treatment for motor symptoms of Parkinson disease (PD), a condition associated with increased risk of dysphagia. The effect of DBS on swallowing function has not been comprehensively evaluated using gold-standard imaging techniques, particularly for globus pallidus internus (GPi) DBS. The objective of this retrospective, cross-sectional study was to identify differences in swallowing safety and timing kinematics among PD subjects with and without GPi DBS. We investigated the effects of unilateral and bilateral GPi DBS as well as the relationship between swallowing safety and DBS stimulation parameters, using retrospective analysis of videofluoroscopy recordings (71 recordings from 36 subjects) from electronic medical records. Outcomes were analyzed by surgical status (pre-surgical, unilateral DBS, bilateral DBS). The primary outcome was percent of thin-liquid bolus trials rated as unsafe, with Penetration-Aspiration Scale scores of 3 or higher. Secondary analyses included swallowing timing measures, relationships between swallowing safety and DBS stimulation parameters, and Dynamic Imaging Grade of Swallowing Toxicity ratings. Most subjects swallowed all boluses safely (19/29 in the pre-surgical, 16/26 in the unilateral DBS, and 10/16 in the bilateral DBS conditions). Swallowing safety impairment did not differ among stimulation groups. There was no main effect of stimulation condition on timing metrics, though main effects were found for sex and bolus type. Stimulation parameters were not correlated with swallowing safety. Swallowing efficiency and overall impairment did not differ among conditions. These results provide evidence that GPi DBS does not affect pharyngeal swallowing function. Further, prospective, investigations are needed.

Comparison of a Minimally Invasive Transthoracic Approach and a Surgical Method for Intrapleural Injection of Tumor Cells in Mice.

Intrapleural injections can be used in mice to deliver therapeutic and diagnostic agents and to model human disease processes (for example, pleural fluid accumulation, malignant pleural disease, and lung cancers). In the context of establishing cancer models, minimally invasive methods of intrapleural injection are desirable because inflammation at the injection site can have a major impact on tumor growth and progression. Common approaches for intrapleural injection include surgical exposure of the thoracic wall or the diaphragm prior to injection; however, these invasive procedures require tissue dissection that triggers an undesirable inflammatory response and increases the risk of pneumothorax. While nonsurgical procedures can minimize this concern, 'blind' injections may lead to off target inoculation. In this study, we hypothesized that a minimally invasive transthoracic approach (MI-TT) would produce a tumor distribution and burden similar to that of a surgical transabdominal approach (SX-TA). Prior to performing the procedures on live mice, surgeons were trained using cadavers and terminal procedures. Then a total of 14 nude mice (female, 4 to 6 wk old) were injected with 50 µL (5 million) A549-Luc2 human cancer cells either using the MI-TT (n = 8) or SX-TA (n = 6) approach under carprofen analgesia and isoflurane anesthesia. Our results indicate that with training, a minimally invasive transthoracic approach for intrapleural injection provides more consistent tumor placement and a greater tumor burden than does the surgical method. However, additional studies are necessary to confirm anatomic placement and characterize tumor profiles.

Comparison of Low- and High-temperature Cagewash Cycles for Sanitation of Rodent Housing Equipment in Research Facilities.

Sanitation guidelines for animal research facilities state that disinfection is achieved by application of high-temperature water (143 to 180 °F [62 to 82 °C]) or detergents and disinfectants. However, these guidelines are based on requirements for pasteurization, which may be unnecessarily stringent for the sanitation of nonfood items and do not address the theoretical sanitation potential of water at temperatures below 143 °F (62 °C). Recent literature indicates that water temperatures below 143 °F (62 °C) can also provide effective sanitation. In this study, we compared cagewash cycles at low (100 °F [38 °C] and 120 °F [49 °C]) and high (standard) (180 °F [82 °C]) temperatures and evaluated sanitation efficacy by using ATP swabs and RODAC plates. Low-temperature loads were washed either with or without prior treatment of a chemical disinfectant (10% bleach). The 100 °F (38 °C) cycle was not sufficient for sanitization without bleach pretreatment. However, the 120 °F (49 °C) cycle effectively sanitized cages without bleach pretreatment. Validation of effective sanitation at a lower water temperature (120 °F [49 °C]) can improve cagewash logistics and reduce costs as compared with standard (180 °F [82 °C]) high-temperature cycles.

Emergency ventilator for COVID-19.

The COVID-19 pandemic disrupted the world in 2020 by spreading at unprecedented rates and causing tens of thousands of fatalities within a few months. The number of deaths dramatically increased in regions where the number of patients in need of hospital care exceeded the availability of care. Many COVID-19 patients experience Acute Respiratory Distress Syndrome (ARDS), a condition that can be treated with mechanical ventilation. In response to the need for mechanical ventilators, designed and tested an emergency ventilator (EV) that can control a patient's peak inspiratory pressure (PIP) and breathing rate, while keeping a positive end expiratory pressure (PEEP). This article describes the rapid design, prototyping, and testing of the EV. The development process was enabled by rapid design iterations using additive manufacturing (AM). In the initial design phase, iterations between design, AM, and testing enabled a working prototype within one week. The designs of the 16 different components of the ventilator were locked by additively manufacturing and testing a total of 283 parts having parametrically varied dimensions. In the second stage, AM was used to produce 75 functional prototypes to support engineering evaluation and animal testing. The devices were tested over more than two million cycles. We also developed an electronic monitoring system and with automatic alarm to provide for safe operation, along with training materials and user guides. The final designs are available online under a free license. The designs have been transferred to more than 70 organizations in 15 countries. This project demonstrates the potential for ultra-fast product design, engineering, and testing of medical devices needed for COVID-19 emergency response.

Dysarthria and Speech Intelligibility Following Parkinson's Disease Globus Pallidus Internus Deep Brain Stimulation.

BACKGROUND: Although earlier studies reported variable speech changes following subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients, the effects of globus pallidus internus (GPi) DBS on speech performance in PD remain largely unknown. OBJECTIVE: We aimed to characterize speech changes following PD GPi-DBS. METHODS: We retrospectively analyzed clinical and speech outcomes of 25 PD patients treated with bilateral GPi-DBS at a single center. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), speech subsystem domains (respiratory, laryngeal, resonance, orofacial, rate, prosody, rhythm, and naturalness), and overall speech intelligibility. Scores at baseline were compared with those at 6 months, 1 year, and the longest clinical follow-up available. RESULTS: In the off-medication state, activities of daily living and motor function based on UPDRS II and III significantly improved postoperatively. We observed unique patterns of speech changes in patients with PD following GPi-DBS in the short- (n = 25) and longer-term (n = 8) follow-up periods. Velopharyngeal (resonance), laryngeal components, and prosody worsened after bilateral GPi-DBS (p < 0.015). Speech intelligibility did not worsen after GPi-DBS in the short-term, but there was a trend to deteriorate at long-term follow-up (e.g., one year and beyond). We observed worsening of hypokinetic dysarthria in individual patients. Also, a minority of patients developed stuttering, spastic dysarthria, or ataxic dysarthria. CONCLUSION: Bilateral GPi-DBS worsened several modalities of parkinsonian speech without compromising overall speech intelligibility. GPi-DBS can potentially worsen or induce hypokinetic dysarthria, stuttering, spastic dysarthria, or ataxic dysarthria. GPi-DBS may have different and variable effects on speech function when compared to STN-DBS.

A comprehensive review of the diagnosis and treatment of Parkinson's disease dysphagia and aspiration.

INTRODUCTION: Bulbar dysfunction is common in Parkinson's disease (PD) with more than 80% of affected individuals developing dysphagia during the course of the disease. Symptoms can begin in the preclinical stage and individuals may remain clinically asymptomatic for years. Furthermore, patients may be unaware of swallowing changes, which contributes to the difference between the prevalence of self-reported dysphagia and deficits identified during instrumental evaluations. Dysphagia is underrecognized and contributes to the development of aspiration pneumonia which is the leading cause of death in PD. Dysphagia in PD is complex and not completely understood. Both dopaminergic and nondopaminergic pathways likely underpin dysphagia. AREAS COVERED: This comprehensive review will cover the epidemiology, pathophysiology, clinical evaluation, and expert management of dysphagia and aspiration in patients with PD. EXPERT OPINION: A multidisciplinary team approach is important to properly identify and manage PD dysphagia. Regular clinical screenings with objective instrumental assessments are necessary for early detection of dysphagia. Studies are needed to better understand the mechanism(s) involved in PD dysphagia, establish markers for early detection and progression, and develop evidence-based treatment options.

Respiratory and Laryngeal Function in Teachers: Pre- and Postvocal Loading Challenge.

PURPOSE: The purpose of this study was to examine laryngeal and respiratory physiological changes in teachers before and after a 1-hour vocal loading challenge. METHODS: Twelve teachers completed ratings of vocal tiredness, vocal effort, and produced a reading passage and monologue before and after a 1-hour vocal loading challenge (reading aloud in noise). Sound pressure level, lung volume parameters, cepstral peak prominence, and low/high spectral ratio were measured. RESULTS: After loading, participants significantly increased vocal effort, vocal tiredness, utterance length, and sound pressure level, and significantly decreased % vital capacity/syllable. CONCLUSIONS: Following the 1-hour reading-aloud challenge, tiredness and effort increased. However, lung volume did not change and cepstral peak prominence and low/high spectral ratio remained in the normal range. Future studies are needed to understand the effect of vocal use and vocal loading in teachers.

Sustained-Release Buprenorphine Improves Postsurgical Clinical Condition but Does Not Alter Survival or Cytokine Levels in a Murine Model of Polymicrobial Sepsis.

Cecal ligation and perforation (CLP) is a common technique for studying sepsis in mice. Because of the invasiveness of the procedure and its effects on clinical condition, many animal care and use committees require the use of analgesics with CLP. However, some analgesics have immunomodulatory effects and thus can hinder the overall research outcomes of a project. Here we sought to determine the effects of buprenorphine hydrochloride (Bup HCl) compared with sustained-release buprenorphine (Bup SR) on clinical condition, plasma concentrations of monocyte chemoattractant protein (MCP) 1 and IL6, and overall mortality in a murine CLP model of sepsis. Male C57/BL6 mice underwent CLP surgery and received Bup HCl or Bup SR as a component of an IACUCapproved analgesic dosing regimen. Mice were observed twice daily for clinical condition scoring by the same blinded investigator for the duration of the study. MCP1 and IL6 levels and mortality did not differ significantly between the 2 groups. Scoring of clinical condition revealed a significant decrease in behaviors associated with perceived pain at 12 and 24 h postoperatively in mice in the Bup SR group compared with the Bup HCl group. Because of the lack of significant effect on MCP1 and IL6 levels and mortality and the superior analgesic effects of Bup SR, we recommend the use of Bup SR for analgesia during the murine CLP model of sepsis.