Awareness of errors is reduced by sleep loss.

The ability to detect and subsequently correct errors is important in preventing the detrimental consequences of sleep loss. The Error Related Negativity (ERN), and the error positivity (Pe) are established neural correlates of error processing. Previous work has shown sleep loss reduces ERN and Pe, indicating sleep loss impairs error-monitoring processes. However, no previous work has examined behavioral error awareness, in conjunction with EEG measures, under sleep loss conditions, and studies of sleep restriction are lacking. Using combined behavioral and EEG measures, we report two studies investigating the impact of total sleep deprivation (TSD) and sleep restriction (SR) on error awareness. Fourteen healthy participants completed the Error Awareness Task under conditions of TSD and 27 completed the same task under conditions of SR. It was found that TSD did not influence behavioral error awareness or ERN or Pe amplitude, however, SR reduced behavioral error awareness, increased the time taken to detect errors, and reduced Pe amplitude. Findings indicate individuals who are chronically sleep restricted are at risk for reduced recognition of errors. Reduced error awareness may be one factor contributing to the increased accidents and injuries seen in contexts where sleep loss is prevalent.

Multimodal assessment of tinnitus using functional near-infrared spectroscopy and psychophysiological measures.

OBJECTIVE: To use a multimodal approach to classify individuals with tinnitus from controls, and individuals with mild versus severe tinnitus. DESIGN: We have previously shown feasibility of a non-invasive imaging technique called functional near-infrared spectroscopy (fNIRS) to detect tinnitus-related changes in cortical activity and classify individuals with tinnitus from controls, as well as individuals with mild versus severe tinnitus. In this study we have used a multimodal approach by recording heart rate, heart rate variability and skin conductance, in addition to fNIRS signals, from individuals with tinnitus and controls. STUDY SAMPLE: Twenty-seven participants with tinnitus and 21 controls were recruited. RESULTS: Our findings show, addition of heart rate measures can improve accuracy of classifying tinnitus severity, in particular loudness as rated subjectively. The f1-score, a measure of classification accuracy, increased from 0.73 to 0.86 when using a support vector machine classifier for differentiating low versus high tinnitus loudness. CONCLUSIONS: Subjective tinnitus is a condition that can only be described by the individual experiencing it, as there are currently no objective measures to determine tinnitus presence and severity, or assess the effectiveness of treatments. Objective measurement of tinnitus is a critical step in developing reliable treatments for this debilitating condition.

Assessing the post hoc effectiveness of tixagevimab-cilgavimab for prevention of SARS-CoV-2 infections in solid organ transplant recipients.

BACKGROUND: Tixagevimab-cilgavimab (Tix-Cil) was authorized for prophylaxis against COVID-19 in immunocompromised patients from December 2021 through January 2023. Real-world effectiveness for solid organ transplant (SOT) recipients has been unclear. METHODS: We enrolled 911 SOT recipients into a longitudinal COVID-19 serology study, of whom 381 (42%) received ≥1 dose of Tix-Cil. We collected and analyzed data on incident SARS-CoV-2 infections and antibody kinetics for all patients from January 2022 to March 2023, including periods dominated by Omicron BA and BQ subvariants. RESULTS: Over 253 ± 131 days of follow-up, there were 324 new-onset SARS-CoV-2 infections: 117 (31%) in Tix-Cil treated and 207 (39%) in Tix-Cil untreated patients (p = .012). In analyses adjusting for demographic, clinical, and COVID-19 exposure factors, any Tix-Cil treatment was associated with lower infection risk (OR 0.52, 95% CI 0.27-0.96, p = .039) throughout the surveillance period including when more resistant BQ.1 and BQ.1.1 subvariants had emerged (12/1/2022 onwards). Among treated patients, receiving a Tix-Cil dose was associated with substantial and sustained increase in anti-spike IgG antibody and angiotensin-converting enzyme 2 binding inhibition levels (Abbott Architect assay) that together also demonstrated association with lower infection risk (p = .042). During the full surveillance period, the frequency of infections requiring hospitalization was low overall (N = 26, 2.9% of the total cohort) and not significantly different between Tix-Cil recipients (N = 12, 3.2% of treated patients) and non-Tix-Cil recipients (N = 14, 2.6% of untreated patients) with unadjusted p = .31 for between-group difference. CONCLUSION: In a large cohort of SOT recipients, we found that Tix-Cil reduced infection risk even amidst emergent Omicron subvariants. Additionally, the extent of measurable humoral response to Tix-Cil may indicate relative effectiveness. Pre-exposure monoclonal antibody therapy may represent a strategy that will continue to offer clinical benefit for immunocompromised persons who are known to derive limited protection from vaccinations.

Towards non-invasive peripheral stimulation as a treatment for Parkinson's disease gait.

Non-invasive coordinated reset stimulation (CRS) to the hands has been shown to improve motor ability in Parkinson's patients, but not specific for gait disturbances. The overall aim of the project is the application of vibrotactile CRS to the feet to improve gait impairments in Parkinson's disease. As a first step towards this objective, we showed that vibrotactile stimulation to the feet can elicit a cortical response and have identified differences in younger and older individuals. Our findings suggest the potential for non-invasive peripheral stimulation as a therapeutic technique.Clinical Relevance- This is an important step towards developing a non-invasive stimulation technique for the management of gait disturbances in Parkinson's disease.

Serological response to vaccination in post-acute sequelae of COVID.

BACKGROUND: Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC. METHODS: We prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity. RESULTS: Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden. CONCLUSION: We found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention.

Acute Respiratory Distress Syndrome in Patients with Subarachnoid Hemorrhage: Incidence, Predictive Factors, and Impact on Mortality.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a known predictor of poor outcomes in critically ill patients. We sought to examine the role ARDS plays in outcomes in subarachnoid hemorrhage (SAH) patients. Prior studies investigating the incidence of ARDS in SAH patients did not control for SAH severity. Hence, we sought to determine the incidence ARDS in patients diagnosed with aneurysmal SAH and investigate the predisposing risk factors and impact upon outcomes. METHODS: A retrospective cohort study was conducted using the National Inpatient Sample (NIS) database for the years 2008 to 2014. Multivariate stepwise regression analysis was performed to identify the risk factors and outcome associated with developing ARDS in the setting of SAH. RESULTS: We identified 170,869 patients with non-traumatic subarachnoid hemorrhage, of whom 6962 were diagnosed with ARDS and of those 4829 required mechanical ventilation. ARDS more frequently developed in high grade SAH patients (1.97 ± 0.05 vs. 1.15 ± 0.01; p < 0.0001). Neurologic predictors of ARDS included cerebral edema (OR 1.892, CI 1.180-3.034, p = 0.0035) and medical predictors included cardiac arrest (OR 4.642, CI 2.273-9.482, p < 0.0001) and cardiogenic shock (OR 2.984, CI 1.157-7.696, p = 0.0239). ARDS was associated with significantly worse outcomes (15.5% vs. 52.9% discharged home, 63.0% vs. 40.8% discharged to rehabilitation facility and 21.5% vs. 6.3% in-hospital mortality). CONCLUSION: Patients with SAH who developed ARDS were less likely to be discharged home, more likely to need rehabilitation and had a significantly higher risk of mortality. The identification of risk factors contributing to ARDS is helpful for improving outcomes and resource utilization.

Bihemispheric ischemic strokes in patients with COVID-19.

BACKGROUND: There is emerging evidence that COVID-19 can trigger thrombosis because of a hypercoagulable state, including large-vessel occlusion ischemic strokes. Bihemispheric ischemic stroke is uncommon and is thought to indicate an embolic source. Here, we examine the findings and outcomes of patients with bihemispheric stroke in the setting of COVID-19. METHODS: We performed a retrospective cohort study at a quaternary academic medical center between March 1, 2020, and April 30, 2020. We identified all patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who presented with simultaneous bihemispheric ischemic strokes. RESULTS: Of 637 COVID-19 admissions during the 2-month period, 13 had a diagnosis of acute ischemic stroke, including 5 who developed bihemispheric cerebral infarction. Three of those 5 (60%) were female, median age was 54 (range 41-67), and all five were being managed for severe COVID-19-related pneumonia complicated by acute kidney injury and liver failure before the diagnosis of cerebral infarction was established. Five presented with elevated ferritin, lactate dehydrogenase, and interleukin-6 (IL-6) levels, and four had lymphopenia and elevated D-dimer levels. All patients underwent neuroimaging with computed tomography for persistent depressed mentation, with or without a focal neurologic deficit, demonstrating multifocal ischemic strokes with bihemispheric involvement. Outcome was poor in all patients: two were discharged to a rehabilitation facility with moderate-to-severe disability and three (60%) patients died. CONCLUSIONS: Stroke is implicated in SARS-CoV-2 infection. Although causality cannot be established, we present the imaging and clinical findings of patients with COVID-19 and simultaneous bihemispheric ischemic strokes. Multifocal ischemic strokes with bihemispheric involvement should be considered in COVID-19 patients with severe infection and poor neurologic status and may be associated with poor outcomes.

Impact of pre-ictal antiplatelet therapy use in aneurysmal subarachnoid hemorrhage.

OBJECTIVE: There is limited evidence on the use of antiplatelet therapy (APT) to reduce the risk and morbidity of cerebral aneurysmal rupture. This analysis retrospectively assessed APT use in patients presenting to our institution with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We evaluated the records of 186 patients over 7 years of retrospective data from our tertiary care center and an existing database of patients with aSAH. A total of 18 cases with patients on APT and 168 patients not on APT (controls) were identified. Primary outcomes measured were clinical grade (Hunt and Hess score), radiographic grade (Fisher score), and presence of delayed cerebral ischemia (DCI). Secondary outcomes were modified Rankin score at discharge and at 3 months. DCI from cerebral vasospasm was defined as the occurrence of focal neurological impairment or a decrease in at least 2 points on the Glasgow Coma Scale. Logistic regression models were generated. RESULTS: We found that APT use did not appear to lead to statistically significant differences in initial presentation, including Hunt-Hess score and Fisher grade (2.91 vs 3.06, p = 0.66, and 3.23 vs 3.22, p = 0.96 respectively). In addition, APT use was not associated with increased rates of delayed cerebral ischemia (DCI) (OR 0.27 p = 0.12). Our analysis showed that increased Hunt Hess score and the presence of DCI are both associated with increased mRS at 90 days (OR 2.32 p < 0.001; OR 2.91 p = 0.002). CONCLUSION: The patients in this retrospective observational study did not demonstrate worse outcomes from their aSAH despite APT therapy. Larger prospective studies should be performed to see if this relationship holds and if decreased rates of DCI can be observed.

Late leukoencephalopathy in patients with methanol intoxication / Leucoencefalopatía tardía posterior a intoxicación por metanol

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Obesity paradox, obesity orthodox, and the metabolic syndrome: An approach to unity.

Obesity and the accompanying metabolic syndrome are strongly associated with heightened morbidity and mortality in older adults. In our review of more than 20 epidemiologic studies of major infectious diseases, including leaders such as tuberculosis, community-acquired pneumonia, and sepsis, obesity was associated with better outcomes. A cause-and-effect relationship between over-nutrition and survival with infection is suggested by results of two preliminary studies of infections in mice, where high fat feeding for 8-10 weeks provided much better outcomes. The better outcomes of infections with obesity are reminiscent of many recent studies of "sterile" non-infectious medical and surgical conditions where outcomes for obese patients are better than for their thinner counterparts --- and given the tag "obesity paradox". Turning to the history of medicine and biological evolution, we hypothesize that the metabolic syndrome has very ancient origins and is part of a lifelong metabolic program. While part of that program (the metabolic syndrome) promotes morbidity and mortality with aging, it helps infants and children as well as adults in their fight against infections and recovery from injuries, key roles in the hundreds of centuries before the public health advances of the 20th century. We conclude with speculation on how understanding the biological elements that protect obese patients with infections or injuries might be applied advantageously to thin patients with the same medical challenges.

Heart Rate Responses of High School Students Participating in Surfing Physical Education.

Despite the nation's rising epidemic of childhood obesity and diabetes, schools struggle to promote physical activities that help reduce risks for cardiovascular disease. Emerging data suggest that adopting novel activities into physical education (PE) curriculum may serve as an effective strategy for increasing physical activity in children. The purpose of this investigation was to characterize activity in the water and heart rates (HRs) of high school students participating in surf PE courses. Twenty-four male (n = 20) and female (n = 4) high school students (mean age = 16.7 ± 1.0 years) who were enrolled in surf PE courses at 2 high schools participated in this investigation. Daily measurements of surfing durations, average HR, and maximum HR were made on the students with HR monitors (PolarFT1) over an 8-week period. In addition, HR and activity in the water was evaluated during a single session in a subset of students (n = 11) using a HR monitor (PolarRCX5) and a video camera (Canon HD). Activity and HR were synchronized and evaluated in 5-second intervals during data analyses. The average duration that PE students participated in surfing during class was 61.7 ± 1.0 minutes. Stationary, paddling, wave riding, and miscellaneous activities comprised 42.7 ± 9.5, 36.7 ± 7.9, 2.9 ± 1.4, and 17.8 ± 11.4 percent of the surf session, respectively. The average and maximum HRs during these activities were 131.1 ± 0.9 and 177.2 ± 1.0 b·min, respectively. These data suggest that high school students participating in surf PE attained HRs and durations that are consistent with recommendations with cardiovascular fitness and health. In the future, PE programs should consider incorporating other action sports into their curriculum to enhance cardiovascular health.

The brighter (and evolutionarily older) face of the metabolic syndrome: evidence from Trypanosoma cruzi infection in CD-1 mice.

BACKGROUND: Infection with Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, results in chronic infection that leads to cardiomyopathy with increased mortality and morbidity in endemic regions. In a companion study, our group found that a high-fat diet (HFD) protected mice from T. cruzi-induced myocardial damage and significantly reduced post-infection mortality during acute T. cruzi infection. METHODS: In the present study metabolic syndrome was induced prior to T. cruzi infection by feeding a high fat diet. Also, mice were treated with anti-diabetic drug metformin. RESULTS: In the present study, the lethality of T. cruzi (Brazil strain) infection in CD-1 mice was reduced from 55% to 20% by an 8-week pre-feeding of an HFD to induce obesity and metabolic syndrome. The addition of metformin reduced mortality to 3%. CONCLUSIONS: It is an interesting observation that both the high fat diet and the metformin, which are known to differentially attenuate host metabolism, effectively modified mortality in T. cruzi-infected mice. In humans, the metabolic syndrome, as presently construed, produces immune activation and metabolic alterations that promote complications of obesity and diseases of later life, such as myocardial infarction, stroke, diabetes, Alzheimer's disease and cancer. Using an evolutionary approach, we hypothesized that for millions of years, the channeling of host resources into immune defences starting early in life ameliorated the effects of infectious diseases, especially chronic infections, such as tuberculosis and Chagas disease. In economically developed countries in recent times, with control of the common devastating infections, epidemic obesity and lengthening of lifespan, the dwindling benefits of the immune activation in the first half of life have been overshadowed by the explosion of the syndrome's negative effects in later life.

Adesão de mulheres mastectomizadas ao início precoce de um programa de reabilitação / Adherence to an early rehabilitation program among women who underwent mastectomy

OBJETIVOS: Verificar a adesão de mulheres mastectomizadas ao início precoce de um programa de reabilitação da amplitude de movimento do ombro homolateral à cirurgia e identificar as dificuldades na realização dos exercícios e das atividades de vida diária. MÉTODOS: Estudo prospectivo desenvolvido no Ambulatório de Oncomastologia do Hospital São Paulo/Universidade Federal de São Paulo, no período de 2003 a 2004. A amostra constitui-se de 28 mulheres mastectomizadas que aceitaram participar do programa de reabilitação, desde a alta hospitalar até o primeiro retorno ambulatorial. RESULTADOS: Aderiram ao programa 64,2 por cento das pacientes e 82,1 por cento referiram dificuldade para execução dos exercícios, principalmente devido à dor. A maioria realizou as atividades de vida diária sem dificuldades. CONCLUSÃO: Faz-se necessário um melhor controle da dor pós-operatória e reforço das orientações para incrementar a adesão das pacientes ao programa de reabilitação.

OBJECTIVES: The main objective was to measure adherence to an early rehabilitation program among women who underwent mastectomy. Other specific objectives included the identification of women's difficulties to comply with the exercise prescription and to perform daily life activities, and whether women's adherence to the rehabilitation program was effective in regaining their shoulder's full range of motion on the side of the surgery. METHODS: A prospective study design was used. A sample of 28 women who underwent mastectomy and agreed to participate in an early rehabilitation program from discharge to the first outpatient clinic follow-up participated in the study. Data were collected from 2003 to 2004 in the oncomastology outpatient clinic of the Hospital São Paulo of the University Federal of São Paulo. RESULTS: The majority of women (63.2 percent) adhered to the early rehabilitation program. The majority of women (82.1 percent) also reported having difficulties to perform the prescribed exercise program due to pain but not with daily life activities. CONCLUSION: Pain management and patient education must be addressed to improve adherence to the early rehabilitation program.

OBJETIVOS: Verificar la adhesión de mujeres mastectomizadas al inicio de un programa de rehabilitación temprana de la amplitud de movimiento del hombro homolateral a la cirugía, e identificar las dificultades en la realización de los ejercicios y de las actividades de vida diaria. MÉTODOS: Estudio prospectivo desarrollado en consulta externa de Oncomastología del Hospital São Paulo/Universidade Federal de São Paulo, en el período 2003 al 2004. La muestra se constituyó de 28 mujeres mastectomizadas que aceptaron participar del programa de rehabilitación, desde el alta hospitalario hasta el primer retorno ambulatorio. RESULTADOS: La adhesion al programa fue del 64,2 por ciento de las pacientes y el 82,1 por ciento refirieron dificultad para la ejecución de los ejercicios, principalmente debido al dolor. La mayoría realizó las actividades de vida diaria sin dificultades. CONCLUSION: Se hace necesario un mejor control del dolor post operatorio y refuerzo de las orientaciones para incrementar la adhesión de las pacientes al programa de rehabilitación.

Ethnicity and young age influence the frequency of diabetic ketoacidosis at the onset of type 1 diabetes.

Diabetic ketoacidosis (DKA) may be present at the onset of type 1 diabetes (T1D), increasing both its morbidity and mortality. The aim of this study was to describe the frequency of this complication at the clinical presentation of T1D, as well as possible interfering factors in a multi-ethnic population from Brazil. We have reviewed the medical charts of 545 individuals with T1D diagnosed between 1968 and 2006 from two major local diabetes treatment centers. DKA occurred in 179 patients (32.8%) at the onset of T1D. The frequency of DKA was higher in non-white than white individuals (p<0.0001) and in the younger age groups (