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Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) can markedly reduce muscle rigidity in people with Parkinson's disease (PD); however, the mechanisms mediating this effect are poorly understood. Computational modeling of DBS provides a method to estimate the relative contributions of neural pathway activations to changes in outcomes. In this study, we generated subject-specific biophysical models of GPi DBS (derived from individual 7-T MRI), including pallidal efferent, putamenal efferent, and internal capsule pathways, to investigate how activation of neural pathways contributed to changes in forearm rigidity in PD. Ten individuals (17 arms) were tested off medication under four conditions: off stimulation, on clinically optimized stimulation, and on stimulation specifically targeting the dorsal GPi or ventral GPi. Quantitative measures of forearm rigidity, with and without a contralateral activation maneuver, were obtained with a robotic manipulandum. Clinically optimized GPi DBS settings significantly reduced forearm rigidity (P < 0.001), which aligned with GPi efferent fiber activation. The model demonstrated that GPi efferent axons could be activated at any location along the GPi dorsal-ventral axis. These results provide evidence that rigidity reduction produced by GPi DBS is mediated by preferential activation of GPi efferents to the thalamus, likely leading to a reduction in excitability of the muscle stretch reflex via overdriving pallidofugal output.NEW & NOTEWORTHY Subject-specific computational models of pallidal deep brain stimulation, in conjunction with quantitative measures of forearm rigidity, were used to examine the neural pathways mediating stimulation-induced changes in rigidity in people with Parkinson's disease. The model uniquely included internal, efferent and adjacent pathways of the basal ganglia. The results demonstrate that reductions in rigidity evoked by deep brain stimulation were principally mediated by the activation of globus pallidus internus efferent pathways.

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BACKGROUND: The COVID-19 pandemic responses in jails have forced detention officers to adjust how they approach the confinement and care of individuals while they are incarcerated. One aspect of incarceration affected was detention officers' roles. The aims of this research project were to determine how the COVID-19 pandemic has affected the general duties of detention officers at a Southwest County Jail. Detention officers were recruited via email to participate in an online questionnaire from October to December 2020. Participants answered Likert scale and open-ended questions regarding how the COVID-19 pandemic has affected their job duties. Descriptive statistics and thematic analysis were used to identify themes and patterns in the responses. RESULTS: Among 24 detention officers, 87% indicated agreement that the COVID-19 pandemic has significantly changed the duties of detention officers at CCDF. The most discussed change was the introduction of a 14-day quarantine process for newly incarcerated individuals. The 14-day quarantine increased the workload of detention officers. CONCLUSION: The COVID-19 pandemic responses in jail may have unintended negative consequences for the job duties of detention officers. Current and future pandemic response strategies in jails would benefit from taking staff perspectives into consideration as they are directly impacted by the COVID-19 response strategies put into place. Policy implications are discussed.

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People with Parkinson's disease who have elevated muscle activity during rapid eye movement sleep (REM sleep without atonia) typically have a worse motor and cognitive impairment compared with those with normal muscle atonia during rapid eye movement sleep. This study used tract-based spatial statistics to compare diffusion MRI measures of fractional anisotropy, radial, mean and axial diffusivity (measures of axonal microstructure based on the directionality of water diffusion) in white matter tracts between people with Parkinson's disease with and without rapid eye movement sleep without atonia and controls and their relationship to measures of motor and cognitive function. Thirty-eight individuals with mild-to-moderate Parkinson's disease and 21 matched control subjects underwent ultra-high field MRI (7 T), quantitative motor assessments of gait and bradykinesia and neuropsychological testing. The Parkinson's disease cohort was separated post hoc into those with and without elevated chin or leg muscle activity during rapid eye movement sleep based on polysomnography findings. Fractional anisotropy was significantly higher, and diffusivity significantly lower, in regions of the corpus callosum, projection and association white matter pathways in the Parkinson's group with normal rapid eye movement sleep muscle tone compared with controls, and in a subset of pathways relative to the Parkinson's disease group with rapid eye movement sleep without atonia. The Parkinson's disease group with elevated rapid eye movement sleep muscle tone showed significant impairments in the gait and upper arm speed compared with controls and significantly worse scores in specific cognitive domains (executive function, visuospatial memory) compared with the Parkinson's disease group with normal rapid eye movement sleep muscle tone. Regression analyses showed that gait speed and step length in the Parkinson's disease cohort were predicted by measures of fractional anisotropy of the anterior corona radiata, whereas elbow flexion velocity was predicted by fractional anisotropy of the superior corona radiata. Visuospatial memory task performance was predicted by the radial diffusivity of the posterior corona radiata. These findings show that people with mild-to-moderate severity of Parkinson's disease who have normal muscle tone during rapid eye movement sleep demonstrate compensatory-like adaptations in axonal microstructure that are associated with preserved motor and cognitive function, but these adaptations are reduced or absent in those with increased rapid eye movement sleep motor tone.

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BACKGROUND: Subtle gait deficits can be seen in people with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), a prodromal stage of Parkinson's disease (PD) and related alpha-synucleinopathies. It is unknown if the presence and level of REM sleep without atonia (RSWA, the electromyographic hallmark of RBD) is related to the severity of gait disturbances in people with PD. OBJECTIVE: We hypothesized that gait disturbances in people with mild-to-moderate PD would be greater in participants with RSWA compared to those without RSWA and matched controls, and that gait impairment would correlate with measures of RSWA. METHODS: Spatiotemporal characteristics of gait were obtained from 41 people with PD and 21 age-matched controls. Overnight sleep studies were used to quantify muscle activity during REM sleep and group participants with PD into those with RSWA (PD-RSWA+, n = 22) and normal REM sleep muscle tone (PD-RSWA-, n = 19). Gait characteristics were compared between groups and correlated to RSWA. RESULTS: The PD-RSWA+ group demonstrated significantly reduced gait speed and step lengths and increased stance and double support times compared to controls, and decreased speed and cadence and increased stride velocity variability compared to PD-RSWA- group. Larger RSWA scores were correlated with worse gait impairment in the PD group. CONCLUSION: The presence and level of muscle tone during REM sleep is associated with the severity of gait disturbances in PD. Pathophysiological processes contributing to disordered gait may occur earlier and/or progress more rapidly in people with PD and RBD.

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OBJECTIVE: Increased muscle activity during rapid eye movement (REM) sleep (i.e. REM sleep without atonia) is common in people with Parkinson's disease (PD). This study tested the hypotheses that people with PD and REM sleep without atonia (RSWA) would present with more severe and symmetric rigidity compared to individuals with PD without RSWA and age-matched controls. METHODS: Sixty-one individuals participated in this study (41 PD, 20 controls). An overnight sleep study was used to classify participants with PD as having either elevated (PD-RSWA+) or normal muscle activity (PD-RSWA-) during REM sleep. Quantitative measures of rigidity were obtained using a robotic manipulandum that passively pronated and supinated the forearm. RESULTS: Quantitative measures of forearm rigidity were significantly higher in the PD-RSWA+ group compared to the control group. Rigidity was significantly more asymmetric between limbs in the PD-RSWA- group compared with controls, while there was no significant difference in symmetry between the control and PD-RSWA+ groups. CONCLUSION: In people with mild to moderate PD, RSWA is associated with an increased and more symmetric presentation of upper limb rigidity. SIGNIFICANCE: Dysfunction of brainstem systems that control muscle tone during REM sleep may contribute to increased rigidity during wakefulness in people with PD.

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OBJECTIVE: Cisplatin is widely used to treat a variety of pediatric solid tumors. One of the most severe and debilitating adverse drug reactions experienced by patients who receive cisplatin therapy is permanent bilateral hearing loss. The aim of this study was to evaluate the incidence and risk factors for cisplatin-induced hearing loss in Mexican pediatric patients. METHODS: Detailed medical and drug histories, including use of cisplatin as well as other drugs known to cause hearing loss, were collected from patient medical records. Results of audiology tests on pediatric patients with solid tumors were collected at baseline, during treatment and at the end of cisplatin chemotherapy. Hearing loss was classified according to the Common Terminology Criteria for Adverse Events. Bivariate and multivariate analyses were performed using survival curves. RESULTS: Fifty-nine pediatric patients, median age 11 years (range, 3-17 years) were included in the study. The incidence of cisplatin-induced hearing loss was 56%. Individual risk factors including age (< 5 years), male sex, and concomitant medications were not associated with an increased risk of cisplatin-induced hearing loss. Patients with a diagnosis of osteosarcoma and a cumulative cisplatin dose greater than 400 mg/m(2) were at higher risk of hearing loss compared with all other tumor and cumulative dose combinations (HR = 2.47 [95% CI, 1.043-5.831]). CONCLUSIONS: Cumulative dose and tumor type are associated with an increased risk of cisplatin-induced hearing loss. Further research is required to characterize fully the interindividual variation in hearing loss in Mexican patients.

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Introducción. La sordera congénita es un problema de salud pública. Su incidencia en México es de 2-3 por cada 1000 recién nacidos. El diagnóstico oportuno con el tamiz auditivo neonatal es fundamental para un mejor pronóstico funcional. Aproximadamente 70% de las sorderas congénitas son de origen genético, con herencia autosómica recesiva. La mayoría de estos casos se asocia con mutaciones en el gen GJB2 , que codifica para la proteína conexina 26. Hay tres mutaciones reportadas como las más frecuentes en este gen: c.35delG, c.167delT y c.235delC. Métodos. Previo consentimiento informado de los pacientes, se obtuvo 1 ml de sangre periférica para la extracción de ADN. Mediante las técnicas de PCR-RFLP o PCR seguida de secuenciación, se buscaron las tres mutaciones más frecuentes del gen GJB2 . Resultados. Se realizó el estudio molecular en 11 pacientes: Se encontró un cambio en la secuencia codificante en cinco de ellos. Un paciente fue homocigoto para c.35delG; otro resultó heterocigoto para c.35insG, mutación no reportada previamente; un tercero fue heterocigoto para c.34G>T y dos más fueron heterocigotos para el polimorfismo c.79G>A (p.V27I). En ningún caso se hallaron las mutaciones c.167delT y c.235delC. Conclusiones. Se encontraron cambios de secuencias que correspondieron a dos polimorfismos y a tres mutaciones. La frecuencia de las tres mutaciones investigadas fue menor a lo reportado en la literatura y se encontró una mutación no reportada previamente. Este estudio evidencia la importancia del diagnóstico oportuno con manejo integral, incluyendo el asesoramiento genético con base en estudios moleculares, y resalta la importancia de conocer el perfil genotípico de este grupo de pacientes.

Background. Congenital deafness is a public health problem affecting 2-3:1000 newborns in Mexico. Neonatal audiologic screening allows early detection with important implications for the functional prognosis. About 70% of cases of congenital deafness are associated with a genetic etiology with an autosomal recessive pattern of inheritance. Most cases are caused by mutations in the GJB2 gene, which codifies conexin 26. The three most commonly reported mutations in this gene are c.35delG, c.167delT and c.235delC. Methods. After obtaining informed consent, DNA was extracted from a blood sample, and the three previously mentioned mutations were searched for using PCR-RFLP or PCR followed by sequencing. Results. Molecular analysis was carried out in 11 patients. In five of these patients, a change in sequence was observed. In none of the patients were c.167delT and c.235delC mutations found. One patient was homozygous for c.35delG and another patient was heterozygous for c.35insG, which is a mutation not previously reported. A third patient was heterozygous for c.34G>T. Two additional patients had the c.79G>A (p.V27I) polymorphism. Conclusions. Frequency of the three mutations analyzed was lower compared to other populations. Five sequence changes were observed, two polymorphisms and three mutations, one of them novel. This study also demonstrates the relevance of early diagnosis and multidisciplinary management and the importance of determining the genetic basis of this disease in pediatric patients with congenital deafness.

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Transmissible viral proventriculitis (TVP) was experimentally reproduced in 2-wk-old specific-pathogen-free chickens and commercial broiler chickens by eyedrop inoculation of adenovirus-like virus (AdLV), isolate R1 1/3. No clinical signs and no weight gain depression were observed in chickens inoculated with AdLV (R11/3); however, gross and microscopic lesions characteristic of TVP were present in proventriculi of inoculated chickens. Proventriculi of AdLV (R11/3)-inoculated chickens were markedly enlarged, compared with sham-inoculated controls, by day 7 postinoculation (PI). Microscopic lesions in proventriculi of inoculated chickens were detected beginning on day 3 PI and consisted of degeneration and necrosis of glandular epithelium, ductal epithelial hyperplasia, replacement of glandular epithelium with ductal epithelium, and diffuse interstitial lymphoid infiltration; no microscopic lesions were observed in other tissues. AdLV (R11/3) antigens were detected in proventriculi by immunohistochemistry on days 3-10 PI in inoculated SPF chickens and days 3-21 PI in inoculated commercial broiler chickens; no viral antigens were detected in other tissues. AdLV (R11/3) was reisolated from proventriculi of inoculated SPF and commercial broiler chickens on days 5 and 7 PI. No virus, viral antigens, or lesions were detected in proventriculi collected from sham-inoculated chickens. These findings indicate an etiologic role for AdLV (R11/3) in TVP.

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The behavior of 643 pedestrians and 1749 motorists at two signal-controlled intersections was observed over a 2-mo. period of observation in March and November. One intersection had a coffin-shaped traffic sign with the wording "Fatality" erected during the first month of observation (March). The second intersection was identical in traffic and pedestrian volume but lacked a "Fatality" sign in either March or November. "Fatality" signs are erected and maintained by the City of Edmonton for 6 mo. whenever a pedestrian death has occurred, and they are intended to raise the awareness of both pedestrians and motorists concerning the risks at dangerous intersections. This sign had been removed for nearly 3 mo. when a follow-up observation was made in November. While female pedestrians and pedestrians over the age of 50 years showed greater caution at both intersections, the presence or absence of the "Fatality" sign had no statistically significant influence on safety. Similarly, the presence or absence of a sign did not significantly influence motorists' behavior. Of motorists 7.6% ran either amber or red traffic control lights at the two intersections. The "Fatality" sign did not affect the rates of these violations.

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BACKGROUND: Hemodynamic instability remains a prominent concern for surgeons performing coronary surgery without cardiopulmonary bypass. The purpose of this study was to further elucidate the mechanism of hemodynamic instability by comparing vacuum stabilization to mechanical stabilization. METHODS: Four 60-kg swine were placed under general anesthesia. A median sternotomy incision was made, and baseline hemodynamic measurements were recorded. Mechanical and vacuum stabilization of the circumflex distribution were alternately compared with repeated baseline measurements in a counterbalanced method, and 32 experiments were conducted. RESULTS: There were significant differences between baseline hemodynamics and stabilized hemodynamics for mechanical stabilization versus vacuum stabilization, respectively, for the following parameters: blood pressure (mean decrement), -32.18% (P =.0028) versus -31.3% (P =.0006); cardiac output, -31.03% (P =.0046) versus -35.2% (P =.03); and mixed venous oxygen saturation, -29.8% (P =.008) versus -27.4% (P =.0004). There were no statistical differences between mechanical and vacuum stabilization when their decremental effects on baseline hemodynamics were compared with each other for any of the measured variables. CONCLUSIONS: The mechanisms of hemodynamic compromise during coronary stabilization remain to be fully elucidated. Our study demonstrates no statistical difference between vacuum and mechanical stabilization on the measured hemodynamic values. More sophisticated studies involving detailed analysis of motion and geometry are required so that technical solutions to hemodynamic instability can be developed.

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