Simultaneous Surgical Approach with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients with Concurrent Peritoneal and Liver Metastases of Colon Cancer Origin.

Background: Simultaneous liver resection and peritoneal cytoreduction with hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial today. The aim of the study was to analyze the postoperative outcomes and survival of patients with advanced metastatic colon cancer (peritoneal and/or liver metastases). Methods: Retrospective observational study from a prospective maintained data base. Patients who underwent a simultaneous peritoneal cytoreduction and liver resection plus HIPEC were studied. Postoperative outcomes and overall and disease free survival were analyzed. Univariate and multivariate analyses were performed. Results: From January 2010 to October 2022, 22 patients operated with peritoneal and liver metastasis (LR+) were compared with 87 patients operated with peritoneal metastasis alone (LR-). LR+ group presented higher serious morbidity (36.4 vs. 14.9%; p: 0.034). Postoperative mortality did not reach statistical difference. Median overall and disease free survival was similar. Peritoneal carcinomatosis index was the only predictive factor of survival. Conclusions: Simultaneous peritoneal and liver resection is associated with increased postoperative morbidity and hospital stay, but with similar postoperative mortality and OS and disease free survival. These results reflect the evolution of these patients, considered inoperable until recently, and justify the trend to incorporate this surgical strategy within a multimodal therapeutic plan in highly selected patients.

Association of biological sex with clinical outcomes and biomarkers of Alzheimer's disease in adults with Down syndrome.

The study of sex differences in Alzheimer's disease is increasingly recognized as a key priority in research and clinical development. People with Down syndrome represent the largest population with a genetic link to Alzheimer's disease (>90% in the 7th decade). Yet, sex differences in Alzheimer's disease manifestations have not been fully investigated in these individuals, who are key candidates for preventive clinical trials. In this double-centre, cross-sectional study of 628 adults with Down syndrome [46% female, 44.4 (34.6; 50.7) years], we compared Alzheimer's disease prevalence, as well as cognitive outcomes and AT(N) biomarkers across age and sex. Participants were recruited from a population-based health plan in Barcelona, Spain, and from a convenience sample recruited via services for people with intellectual disabilities in England and Scotland. They underwent assessment with the Cambridge Cognitive Examination for Older Adults with Down Syndrome, modified cued recall test and determinations of brain amyloidosis (CSF amyloid-ß 42 / 40 and amyloid-PET), tau pathology (CSF and plasma phosphorylated-tau181) and neurodegeneration biomarkers (CSF and plasma neurofilament light, total-tau, fluorodeoxyglucose-PET and MRI). We used within-group locally estimated scatterplot smoothing models to compare the trajectory of biomarker changes with age in females versus males, as well as by apolipoprotein ɛ4 carriership. Our work revealed similar prevalence, age at diagnosis and Cambridge Cognitive Examination for Older Adults with Down Syndrome scores by sex, but males showed lower modified cued recall test scores from age 45 compared with females. AT(N) biomarkers were comparable in males and females. When considering apolipoprotein ɛ4, female ɛ4 carriers showed a 3-year earlier age at diagnosis compared with female non-carriers (50.5 versus 53.2 years, P = 0.01). This difference was not seen in males (52.2 versus 52.5 years, P = 0.76). Our exploratory analyses considering sex, apolipoprotein ɛ4 and biomarkers showed that female ɛ4 carriers tended to exhibit lower CSF amyloid-ß 42/amyloid-ß 40 ratios and lower hippocampal volume compared with females without this allele, in line with the clinical difference. This work showed that biological sex did not influence clinical and biomarker profiles of Alzheimer's disease in adults with Down syndrome. Consideration of apolipoprotein ɛ4 haplotype, particularly in females, may be important for clinical research and clinical trials that consider this population. Accounting for, reporting and publishing sex-stratified data, even when no sex differences are found, is central to helping advance precision medicine.

Empathy as a crucial skill in disrupting disparities in global brain health.

Brain health refers to the state of a person's brain function across various domains, including cognitive, behavioral and motor functions. Healthy brains are associated with better individual health, increased creativity, and enhanced productivity. A person's brain health is intricately connected to personal, social and environmental factors. Racial, ethnic, and social disparities affect brain health and on the global scale these disparities within and between regions present a hurdle to brain health. To overcome global disparities, greater collaboration between practitioners and healthcare providers and the people they serve is essential. This requires cultural humility driven by empathy. Empathy is a core prosocial value, a cognitive-emotional skill that helps us understand ourselves and others. This position paper aims to provide an overview of the vital roles of empathy, cooperation, and interdisciplinary partnerships. By consciously integrating this understanding in practice, leaders can better position themselves to address the diverse challenges faced by communities, promote inclusivity in policies and practices, and further more equitable solutions to the problem of global brain health.

Neural correlates of episodic memory in adults with Down syndrome and Alzheimer's disease.

BACKGROUND: Adults with Down syndrome are at an ultra-high risk of developing early-onset Alzheimer's disease. Episodic memory deficits are one of the earliest signs of the disease, but their association with regional brain atrophy in the population with Down syndrome has not been explored. We aimed to investigate the neuroanatomical correlates of episodic memory in adults with Down syndrome and symptomatic Alzheimer's disease. METHODS: Single-center, cross-sectional study. A total of 139 adults with Down syndrome (85 asymptomatic and 54 with symptomatic Alzheimer's disease) were included in the study (mean age 43.6 ± 10.9 years, 46% female). Episodic memory was assessed using the modified Cued Recall Test. Immediate (trial 1 free immediate recall, trial 3 free immediate recall, total free immediate recall score, and total immediate score) and delayed scores (free delayed recall score and total delayed score) were examined. Cortical thickness from magnetic resonance imaging was determined with surface-based morphometry using the FreeSurfer 6.0 software package. The clusters of reduced cortical thickness were compared between symptomatic and asymptomatic participants to create a cortical atrophy map. Then, the correlation between cortical thickness and the modified Cued Recall Test subscores were separately assessed in symptomatic and asymptomatic subjects, controlling for age, sex, and severity of intellectual disability. RESULTS: Compared with asymptomatic participants, those with symptomatic Alzheimer's disease showed a pattern of cortical atrophy in posterior parieto-temporo-occipital cortices. In symptomatic subjects, trial 1 immediate free recall significantly correlated with cortical atrophy in lateral prefrontal regions. Trial 3 free immediate recall and total free immediate recall were associated with the most widespread cortical atrophy. Total immediate score was related to posterior cortical atrophy, including lateral parietal and temporal cortex, posterior cingulate cortex, precuneus, and medial temporal lobe areas. Delayed memory scores were associated with cortical atrophy in temporoparietal and medial temporal lobe regions. No significant relationships were observed between episodic memory measures and cortical atrophy in asymptomatic subjects. CONCLUSIONS: Different episodic memory measures were associated with cortical atrophy in specific brain regions in adults with Down syndrome and Alzheimer's disease. These results overlap with those described in sporadic Alzheimer's disease and further support the similarities between Down syndrome-associated Alzheimer's disease and that in the general population.

Feasibility and Long-Term Compliance to Continuous Positive Airway Pressure Treatment in Adults With Down Syndrome, a Genetic Form of Alzheimer's Disease.

Background: Down syndrome (DS) is a genetic form of Alzheimer's disease (AD) with a high prevalence of obstructive sleep apnea (OSA). These characteristics place the DS population as an optimal model to study the relationship between sleep and AD and to design clinical trials of preventive sleep therapies for AD. Regrettably, OSA treatment with continuous positive airway pressure (CPAP) is often neglected in adults with DS. In both clinical practice and research trials, it is usually presumed that these patients will not adapt to or tolerate the therapy. Study Objective: We aimed to evaluate the feasibility and long-term CPAP compliance in this population and their capacity to be enrolled in CPAP research studies. Methods: We prospectively compared the CPAP compliance of 17 OSA patients with DS and 19 age and sex matched OSA euploid patients. CPAP management and follow-up schedules were prescribed according to the habitual clinical practice. We compared group differences in tolerance, objective, and subjective hours of nightly CPAP usage at the 1st, 3rd, 6th, 12th, 24th, and 36th month visits. Good compliance was defined as at least 4 h use per night. We also investigated predictive factors of long-term CPAP compliance. Results: The percentage of DS subjects with good CPAP compliance (81.2 vs. 78.9%) and the objective CPAP use (5 vs. 6 h, p = 0.92) did not differ from the control group (CG). Subjective CPAP compliance was significantly higher in OSA patients with DS than in controls in all the follow-up visits (8 vs. 6.75 h, p = 0.001). The DS group had a significantly higher number of visits (9 vs. 5; p = 0.021) and mask changes (2.5 vs. 2; p = 0.05) than controls. Objective hours of CPAP use at the first follow-up visit predicted long-term CPAP compliance (p < 0.005). Conclusion: CPAP treatment is feasible and has good long-term compliance in OSA patients with DS. It should be recommended to improve health and prevent comorbidities. The DS population is indeed suitable to participate in longitudinal preventive sleep clinical trials for AD.

Opportunities, barriers, and recommendations in down syndrome research.

BACKGROUND: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community. OBJECTIVE: The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan. METHODS: NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS. RESULTS: This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade. CONCLUSIONS: This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy.

Association of Apolipoprotein E ɛ4 Allele With Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults With Down Syndrome.

Importance: Alzheimer disease (AD) is the leading cause of death in individuals with Down syndrome (DS). Previous studies have suggested that the APOE ɛ4 allele plays a role in the risk and age at onset of dementia in DS; however, data on in vivo biomarkers remain scarce. Objective: To investigate the association of the APOE ɛ4 allele with clinical and multimodal biomarkers of AD in adults with DS. Design, Setting, and Participants: This dual-center cohort study recruited adults with DS in Barcelona, Spain, and in Cambridge, UK, between June 1, 2009, and February 28, 2020. Included individuals had been genotyped for APOE and had at least 1 clinical or AD biomarker measurement; 2 individuals were excluded because of the absence of trisomy 21. Participants were either APOE ɛ4 allele carriers or noncarriers. Main Outcomes and Measures: Participants underwent a neurological and neuropsychological assessment. A subset of participants had biomarker measurements: Aß1-42, Aß1-40, phosphorylated tau 181 (pTau181) and neurofilament light chain (NfL) in cerebrospinal fluid (CSF), pTau181, and NfL in plasma; amyloid positron emission tomography (PET); fluorine 18-labeled-fluorodeoxyglucose PET; and/or magnetic resonance imaging. Age at symptom onset was compared between APOE ɛ4 allele carriers and noncarriers, and within-group local regression models were used to compare the association of biomarkers with age. Voxelwise analyses were performed to assess topographical differences in gray matter metabolism and volume. Results: Of the 464 adults with DS included in the study, 97 (20.9%) were APOE ɛ4 allele carriers and 367 (79.1%) were noncarriers. No differences between the 2 groups were found by age (median [interquartile range], 45.9 [36.4-50.2] years vs 43.7 [34.9-50.2] years; P = .56) or sex (51 male carriers [52.6%] vs 199 male noncarriers [54.2%]). APOE ɛ4 allele carriers compared with noncarriers presented with AD symptoms at a younger age (mean [SD] age, 50.7 [4.4] years vs 52.7 [5.8] years; P = .02) and showed earlier cognitive decline. Locally estimated scatterplot smoothing curves further showed between-group differences in biomarker trajectories with age as reflected by nonoverlapping CIs. Specifically, carriers showed lower levels of the CSF Aß1-42 to Aß1-40 ratio until age 40 years, earlier increases in amyloid PET and plasma pTau181, and earlier loss of cortical metabolism and hippocampal volume. No differences were found in NfL biomarkers or CSF total tau and pTau181. Voxelwise analyses showed lower metabolism in subcortical and parieto-occipital structures and lower medial temporal volume in APOE ɛ4 allele carriers. Conclusions and Relevance: In this study, the APOE ɛ4 allele was associated with earlier clinical and biomarker changes of AD in DS. These results provide insights into the mechanisms by which APOE increases the risk of AD, emphasizing the importance of APOE genotype for future clinical trials in DS.

Sleep Disorders in Adults with Down Syndrome.

Sleep disorders, despite being very frequent in adults with Down syndrome (DS), are often overlooked due to a lack of awareness by families and physicians and the absence of specific clinical sleep guidelines. Untreated sleep disorders have a negative impact on physical and mental health, behavior, and cognitive performance. Growing evidence suggests that sleep disruption may also accelerate the progression to symptomatic Alzheimer's disease (AD) in this population. It is therefore imperative to have a better understanding of the sleep disorders associated with DS in order to treat them, and in doing so, improve cognition and quality of life, and prevent related comorbidities. This paper reviews the current knowledge of the main sleep disorders in adults with DS, including evaluation and management. It highlights the existing gaps in knowledge and discusses future directions to achieve earlier diagnosis and better treatment of sleep disorders most frequently found in this population.

Epilepsy in Down Syndrome: A Highly Prevalent Comorbidity.

Individuals with Down syndrome (DS) have an increased risk for epilepsy during the whole lifespan, but especially after age 40 years. The increase in the number of individuals with DS living into late middle age due to improved health care is resulting in an increase in epilepsy prevalence in this population. However, these epileptic seizures are probably underdiagnosed and inadequately treated. This late onset epilepsy is linked to the development of symptomatic Alzheimer's disease (AD), which is the main comorbidity in adults with DS with a cumulative incidence of more than 90% of adults by the seventh decade. More than 50% of patients with DS and AD dementia will most likely develop epilepsy, which in this context has a specific clinical presentation in the form of generalized myoclonic epilepsy. This epilepsy, named late onset myoclonic epilepsy (LOMEDS) affects the quality of life, might be associated with worse cognitive and functional outcomes in patients with AD dementia and has an impact on mortality. This review aims to summarize the current knowledge about the clinical and electrophysiological characteristics, diagnosis and treatment of epileptic seizures in the DS population, with a special emphasis on LOMEDS. Raised awareness and a better understanding of epilepsy in DS from families, caregivers and clinicians could enable earlier diagnoses and better treatments for individuals with DS.

Diagnosis of prodromal and Alzheimer's disease dementia in adults with Down syndrome using neuropsychological tests.

INTRODUCTION: We aimed to define prodromal Alzheimer's disease (AD) and AD dementia using normative neuropsychological data in a large population-based cohort of adults with Down syndrome (DS). METHODS: Cross-sectional study. DS participants were classified into asymptomatic, prodromal AD and AD dementia, based on neurologist's judgment blinded to neuropsychological data (Cambridge Cognitive Examination for Older Adults with Down's syndrome [CAMCOG-DS] and modified Cued Recall Test [mCRT]). We compared the cutoffs derived from the normative data in young adults with DS to those from receiver-operating characteristic curve (ROC) analysis. RESULTS: Diagnostic performance of the CAMCOG-DS and modified Cued Recall Test (mCRT) in subjects with mild and moderate levels of intellectual disability (ID) was high, both for diagnosing prodromal AD and AD dementia (area under the curve [AUC] 0.73-0.83 and 0.90-1, respectively). The cutoffs derived from the normative data were similar to those derived from the ROC analyses. DISCUSSION: Diagnosing prodromal AD and AD dementia in DS with mild and moderate ID using population norms for neuropsychological tests is possible with high diagnostic accuracy.

Clinical and biomarker changes of Alzheimer's disease in adults with Down syndrome: a cross-sectional study.

BACKGROUND: Alzheimer's disease and its complications are the leading cause of death in adults with Down syndrome. Studies have assessed Alzheimer's disease in individuals with Down syndrome, but the natural history of biomarker changes in Down syndrome has not been established. We characterised the order and timing of changes in biomarkers of Alzheimer's disease in a population of adults with Down syndrome. METHODS: We did a dual-centre cross-sectional study of adults with Down syndrome recruited through a population-based health plan in Barcelona (Spain) and through services for people with intellectual disabilities in Cambridge (UK). Cognitive impairment in participants with Down syndrome was classified with the Cambridge Cognitive Examination for Older Adults with Down Syndrome (CAMCOG-DS). Only participants with mild or moderate disability were included who had at least one of the following Alzheimer's disease measures: apolipoprotein E allele carrier status; plasma concentrations of amyloid ß peptides 1-42 and 1-40 and their ratio (Aß1-42/1-40), total tau protein, and neurofilament light chain (NFL); tau phosphorylated at threonine 181 (p-tau), and NFL in cerebrospinal fluid (CSF); and one or more of PET with 18F-fluorodeoxyglucose, PET with amyloid tracers, and MRI. Cognitively healthy euploid controls aged up to 75 years who had no biomarker abnormalities were recruited from the Sant Pau Initiative on Neurodegeneration. We used a first-order locally estimated scatterplot smoothing curve to determine the order and age at onset of the biomarker changes, and the lowest ages at the divergence with 95% CIs are also reported where appropriate. FINDINGS: Between Feb 1, 2013, and June 28, 2019 (Barcelona), and between June 1, 2009, and Dec 31, 2014 (Cambridge), we included 388 participants with Down syndrome (257 [66%] asymptomatic, 48 [12%] with prodromal Alzheimer's disease, and 83 [21%] with Alzheimer's disease dementia) and 242 euploid controls. CSF Aß1-42/1-40 and plasma NFL values changed in individuals with Down syndrome as early as the third decade of life, and amyloid PET uptake changed in the fourth decade. 18F-fluorodeoxyglucose PET and CSF p-tau changes occurred later in the fourth decade of life, followed by hippocampal atrophy and changes in cognition in the fifth decade of life. Prodromal Alzheimer's disease was diagnosed at a median age of 50·2 years (IQR 47·5-54·1), and Alzheimer's disease dementia at 53·7 years (49·5-57·2). Symptomatic Alzheimer's disease prevalence increased with age in individuals with Down syndrome, reaching 90-100% in the seventh decade of life. INTERPRETATION: Alzheimer's disease in individuals with Down syndrome has a long preclinical phase in which biomarkers follow a predictable order of changes over more than two decades. The similarities with sporadic and autosomal dominant Alzheimer's disease and the prevalence of Down syndrome make this population a suitable target for Alzheimer's disease preventive treatments. FUNDING: Instituto de Salud Carlos III, Fundació Bancaria La Caixa, Fundació La Marató de TV3, Medical Research Council, and National Institutes of Health.

The Sant Pau Initiative on Neurodegeneration (SPIN) cohort: A data set for biomarker discovery and validation in neurodegenerative disorders.

INTRODUCTION: The SPIN (Sant Pau Initiative on Neurodegeneration) cohort is a multimodal biomarker platform designed for neurodegenerative disease research following an integrative approach. METHODS: Participants of the SPIN cohort provide informed consent to donate blood and cerebrospinal fluid samples, receive detailed neurological and neuropsychological evaluations, and undergo a structural 3T brain MRI scan. A subset also undergoes other functional or imaging studies (video-polysomnogram, 18F-fluorodeoxyglucose PET, amyloid PET, Tau PET). Participants are followed annually for a minimum of 4 years, with repeated cerebrospinal fluid collection and imaging studies performed every other year, and brain donation is encouraged. RESULTS: The integration of clinical, neuropsychological, genetic, biochemical, imaging, and neuropathological information and the harmonization of protocols under the same umbrella allows the discovery and validation of key biomarkers across several neurodegenerative diseases. DISCUSSION: We describe our particular 10-year experience and how different research projects were unified under an umbrella biomarker program, which might be of help to other research teams pursuing similar approaches.

Analysis of shyness on vocal handicap perceived in school teachers. / Análise da timidez na desvantagem vocal percebida em professores.

PURPOSE: To verify the relation between the self-reported shyness and perceived vocal handicap in teachers from Early childhood and Primary education (elementary and middle school). METHODS: 200 teachers (mean age 41.8 years old) without vocal complaint answered to personal identification protocol, work characterization information, the Vocal Handcap Index and the Shyness Scale. RESULTS: From the total sample, 142 (71%) teachers had no vocal disadvantage, 42% (n = 59) were shy and 58% (n = 83) were non-shy. Among the 58 (29%) teachers with vocal disadvantage, most of them were shy (64%) instead of non-shy (26%). Considering the shy teachers, most of them worked in Early Childhood Education, were aged between 20-30 years old, had from 1 to 10 years of teaching experience and were working in a noisy classroom. The presence of upper airway affections was more frequent in shy teachers without vocal disadvantage and this was the only aspect that differentiated shy and non-shy teachers. CONCLUSION: Shy teachers showed higher frequency of vocal disadvantage when compared to non-shy teachers. Teachers between 20 and 30 years old, with up to 10 years of teaching experience and who teach in Early Childhood Education reported shyness, but there was no relation with vocal disadvantage.

OBJETIVO: Verificar a relação entre a timidez autorreferida e a desvantagem vocal percebida em professores da Educação Infantil e Fundamental I e II. MÉTODO: 200 professores (média de 41,8 anos), sem queixa vocal atual, preencheram 3 protocolos: uma ficha de identificação pessoal e caracterização do trabalho, composta por 11 questões, elaborada pelo Programa de Saúde Vocal do SinproSP; o Índice de Desvantagem Vocal, instrumento de autoavaliação que investiga a autopercepção do impacto de um problema vocal; e a Escala de Timidez, com 14 itens sobre sentimentos e comportamentos comunicativos relacionados ao cotidiano organizacional. RESULTADOS: Do total da amostra, 142 (71%) professores não apresentaram desvantagem vocal, sendo 42% (n=59) professores tímidos e 58% (n=83) não tímidos. Para os 58 (29%) professores que apresentaram desvantagem vocal, houve um maior número de tímidos (64%) do que não tímidos (26%). Entre o total de professores tímidos, houve uma proporção maior destes entre os professores que atuam exclusivamente na Educação Infantil, com faixa etária entre 20-30 anos, formados em até 10 anos e com queixa da presença de ruído na sala de aula. A presença de afecções de vias aéreas superiores foi o único aspecto que diferenciou tímidos com e sem desvantagem vocal, sendo mais frequente nos professores tímidos sem desvantagem vocal. CONCLUSÃO: Professores tímidos percebem mais desvantagem vocal quando comparados aos não tímidos. Os docentes com faixa etária entre 20 e 30 anos, com até 10 anos de formados e que lecionam para Educação Infantil relatam timidez, porém sem associação com a desvantagem vocal.

Alterations in EEG connectivity in healthy young adults provide an indicator of sleep depth.

Current sleep analyses have used electroencephalography (EEG) to establish sleep intensity through linear and nonlinear measures. Slow wave activity (SWA) and entropy are the most commonly used markers of sleep depth. The purpose of this study is to evaluate changes in brain EEG connectivity during sleep in healthy subjects and compare them with SWA and entropy. Four different connectivity metrics: coherence (MSC), synchronization likelihood (SL), cross mutual information function (CMIF), and phase locking value (PLV), were computed focusing on their correlation with sleep depth. These measures provide different information and perspectives about functional connectivity. All connectivity measures revealed to have functional changes between the different sleep stages. The averaged CMIF seemed to be a more robust connectivity metric to measure sleep depth (correlations of 0.78 and 0.84 with SWA and entropy, respectively), translating greater linear and nonlinear interdependences between brain regions especially during slow wave sleep. Potential changes of brain connectivity were also assessed throughout the night. Connectivity measures indicated a reduction of functional connectivity in N2 as sleep progresses. The validation of connectivity indexes is necessary because they can reveal the interaction between different brain regions in physiological and pathological conditions and help understand the different functions of deep sleep in humans.

Análise da timidez na desvantagem vocal percebida em professores / Analysis of shyness on vocal handicap perceived in school teachers

RESUMO Objetivo Verificar a relação entre a timidez autorreferida e a desvantagem vocal percebida em professores da Educação Infantil e Fundamental I e II. Método 200 professores (média de 41,8 anos), sem queixa vocal atual, preencheram 3 protocolos: uma ficha de identificação pessoal e caracterização do trabalho, composta por 11 questões, elaborada pelo Programa de Saúde Vocal do SinproSP; o Índice de Desvantagem Vocal, instrumento de autoavaliação que investiga a autopercepção do impacto de um problema vocal; e a Escala de Timidez, com 14 itens sobre sentimentos e comportamentos comunicativos relacionados ao cotidiano organizacional. Resultados Do total da amostra, 142 (71%) professores não apresentaram desvantagem vocal, sendo 42% (n=59) professores tímidos e 58% (n=83) não tímidos. Para os 58 (29%) professores que apresentaram desvantagem vocal, houve um maior número de tímidos (64%) do que não tímidos (26%). Entre o total de professores tímidos, houve uma proporção maior destes entre os professores que atuam exclusivamente na Educação Infantil, com faixa etária entre 20-30 anos, formados em até 10 anos e com queixa da presença de ruído na sala de aula. A presença de afecções de vias aéreas superiores foi o único aspecto que diferenciou tímidos com e sem desvantagem vocal, sendo mais frequente nos professores tímidos sem desvantagem vocal. Conclusão Professores tímidos percebem mais desvantagem vocal quando comparados aos não tímidos. Os docentes com faixa etária entre 20 e 30 anos, com até 10 anos de formados e que lecionam para Educação Infantil relatam timidez, porém sem associação com a desvantagem vocal.

ABSTRACT Purpose To verify the relation between the self-reported shyness and perceived vocal handicap in teachers from Early childhood and Primary education (elementary and middle school). Methods 200 teachers (mean age 41.8 years old) without vocal complaint answered to personal identification protocol, work characterization information, the Vocal Handcap Index and the Shyness Scale. Results From the total sample, 142 (71%) teachers had no vocal disadvantage, 42% (n = 59) were shy and 58% (n = 83) were non-shy. Among the 58 (29%) teachers with vocal disadvantage, most of them were shy (64%) instead of non-shy (26%). Considering the shy teachers, most of them worked in Early Childhood Education, were aged between 20-30 years old, had from 1 to 10 years of teaching experience and were working in a noisy classroom. The presence of upper airway affections was more frequent in shy teachers without vocal disadvantage and this was the only aspect that differentiated shy and non-shy teachers. Conclusion Shy teachers showed higher frequency of vocal disadvantage when compared to non-shy teachers. Teachers between 20 and 30 years old, with up to 10 years of teaching experience and who teach in Early Childhood Education reported shyness, but there was no relation with vocal disadvantage.

Prevalence of Sleep Disorders in Adults With Down Syndrome: A Comparative Study of Self-Reported, Actigraphic, and Polysomnographic Findings.

STUDY OBJECTIVES: Sleep problems are often undetected in adults with Down syndrome (DS). Our objective was to determine the prevalence of sleep disorders in adults with DS through self-reported and objective sleep measures. METHODS: We performed a community-based cross-sectional study of 54 adults with DS not referred for sleep disorders. Two polysomnography (PSG) sleep studies were performed. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI); daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS) and the risk for the sleep apnea syndrome (OSA) was identified using the Berlin Questionnaire (BQ). Participants' sleep/wake pattern was assessed from sleep diaries and by wrist actigraphy. PSQI, ESS, and PSG measures were compared with 35 sex-, age-, and body mass index-matched patients in the control groups. RESULTS: In PSG measures, adults with DS showed lower sleep efficiency (69 ± 17.7 versus 81.6 ± 11; P < .001), less rapid eye movement sleep (9.4 ± 5.8 versus 19.4 ± 5.1; P < .001), a higher prevalence of OSA (78% versus 14%; P < .001), and a higher apnea-hypopnea index (23.5 ± 24.5 versus 3.8 ± 10.5; P < .001) than patients in the control group. In the DS group, the questionnaires (mean PSQI 3.7 ± 2.9; mean ESS 6.3 ± 4.5 and mean BQ 1 ± 0) did not reflect the sleep disturbances detected on the PSG. Actigraphy data recorded daytime sleep that was not self-reported (118.2 ± 104.2 minutes). CONCLUSIONS: Adults with DS show severe sleep disruption and a high prevalence of OSA, undetected by self-reported sleep measures. Actigraphy, PSG, and validated simplified devices for screening OSA should be routinely recommended for this population because treatment of sleep disorders can contribute to healthy aging.

2,4-Diamino-N10-methylpteroic acid (DAMPA) crystalluria in a patient with osteosarcoma treated with carboxypeptidase-G2 rescue after high-dose methotrexate-induced nephrotoxicity.

BACKGROUND: High-dose methotrexate (HDMTX) therapy is a key component of many chemotherapy protocols. However, some patients develop HDMTX-induced nephrotoxicity. Carboxypeptidase-G2 (CPDG2) hydrolyses MTX into 2,4-diamino-N10-methylpteroic acid (DAMPA) and glutamic acid, and is used as a rescue agent in patients with nephrotoxicity and delayed elimination. Despite the frequency of HDMTX-induced renal injury, crystalluria is uncommon. Furthermore, crystals are rarely identified by conventional chemical methods. OBJECTIVE: To determine the composition of crystalluria in a patient with osteosarcoma who was treated with CPDG2. METHODS: Crystalluria was evaluated by optical microscopy, and chemical identification was performed by Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and Orbitrap™ high-resolution mass spectrometry (HRMS). RESULTS: The HRMS spectra of the patient's urine sediment showed a main peak at m/z 326.13, corresponding to the molecular mass of DAMPA [(C15H15O2N7) + H+]. The FT-IR spectral patterns of the sediment and DAMPA were not identical. SEM was unable to identify the crystal. CONCLUSION: DAMPA crystalluria was identified by Orbitrap™ HRMS in a patient treated with CPDG2 after HDMTX nephrotoxicity. This case reinforces the need to implement adequate measures to prevent nephrotoxicity. In cases of HDMTX-induced nephrotoxicity, urine sediment analysis should be requested.

Monitoring sleep depth: analysis of bispectral index (BIS) based on polysomnographic recordings and sleep deprivation.

The assessment and management of sleep are increasingly recommended in the clinical practice. Polysomnography (PSG) is considered the gold standard test to monitor sleep objectively, but some practical and technical constraints exist due to environmental and patient considerations. Bispectral index (BIS) monitoring is commonly used in clinical practice for guiding anesthetic administration and provides an index based on relationships between EEG components. Due to similarities in EEG synchronization between anesthesia and sleep, several studies have assessed BIS as a sleep monitor with contradictory results. The aim of this study was to evaluate objectively both the feasibility and reliability of BIS for sleep monitoring through a robust methodology, which included full PSG recordings at a baseline situation and after 40 h of sleep deprivation. Results confirmed that the BIS index was highly correlated with the hypnogram (0.89 ± 0.02), showing a progressive decrease as sleep deepened, and an increase during REM sleep (awake: 91.77 ± 8.42; stage N1: 83.95 ± 11.05; stage N2: 71.71 ± 11.99; stage N3: 42.41 ± 9.14; REM: 80.11 ± 8.73). Mean and median BIS values were lower in the post-deprivation night than in the baseline night, showing statistical differences for the slow wave sleep (baseline: 42.41 ± 9.14 vs. post-deprivation: 39.49 ± 10.27; p = 0.02). BIS scores were able to discriminate properly between deep (N3) and light (N1, N2) sleep. BIS values during REM overlapped those of other sleep stages, although EMG activity provided by the BIS monitor could help to identify REM sleep if needed. In conclusion, BIS monitors could provide a useful measure of sleep depth in especially particular situations such as intensive care units, and they could be used as an alternative for sleep monitoring in order to reduce PSG-derived costs and to increase capacity in ambulatory care.

Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Aß42 Levels in Cognitively Normal Elderly.

STUDY OBJECTIVES: Emerging evidence suggests a role for sleep in contributing to the progression of Alzheimer disease (AD). Slow wave sleep (SWS) is the stage during which synaptic activity is minimal and clearance of neuronal metabolites is high, making it an ideal state to regulate levels of amyloid beta (Aß). We thus aimed to examine relationships between concentrations of Aß42 in the cerebrospinal fluid (CSF) and measures of SWS in cognitively normal elderly subjects. METHODS: Thirty-six subjects underwent a clinical and cognitive assessment, a structural MRI, a morning to early afternoon lumbar puncture, and nocturnal polysomnography. Correlations and linear regression analyses were used to assess for associations between CSF Aß42 levels and measures of SWS controlling for potential confounders. Resulting models were compared to each other using ordinary least squared linear regression analysis. Additionally, the participant sample was dichotomized into "high" and "low" Aß42 groups to compare SWS bout length using survival analyses. RESULTS: A significant inverse correlation was found between CSF Aß42 levels, SWS duration and other SWS characteristics. Collectively, total SWA in the frontal lead was the best predictor of reduced CSF Aß42 levels when controlling for age and ApoE status. Total sleep time, time spent in NREM1, NREM2, or REM sleep were not correlated with CSF Aß42. CONCLUSIONS: In cognitively normal elderly, reduced and fragmented SWS is associated with increases in CSF Aß42, suggesting that disturbed sleep might drive an increase in soluble brain Aß levels prior to amyloid deposition.