Clinical dimensions along the non-fluent variant primary progressive aphasia spectrum.

It is debated whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) belong to the same clinical spectrum traditionally termed nonfluent/agrammatic variant primary progressive aphasia (nfvPPA) or exist as two completely distinct syndromic entities with specific pathologic/prognostic correlates. We analyzed speech, language, and disease severity features in a comprehensive cohort of patients with progressive motor speech impairment and/or agrammatism to ascertain evidence of naturally occurring, clinically meaningful non-overlapping syndromic entities (e.g., PPAOS and PAA) in our data. We also assessed if data-driven latent clinical dimensions with etiologic/prognostic value could be identified. We included 98 participants, 43 of whom had an autopsy-confirmed neuropathological diagnosis. Speech pathologists assessed motor speech features indicative of dysarthria and apraxia of speech (AOS). Quantitative expressive/receptive agrammatism measures were obtained and compared with healthy controls. Baseline and longitudinal disease severity was evaluated using the Clinical Dementia Rating sum-of-boxes (CDR-SB). We investigated the data's clustering tendency and cluster stability to form robust symptom clusters and employed principal component analysis to extract data-driven latent clinical dimensions (LCD). The longitudinal CDR-SB change was estimated utilizing linear mixed-effects models. Of the participants included in this study, 93 conformed to previously reported clinical profiles (75 with AOS and agrammatism, 12 PPAOS, and 6 PAA). The remaining five participants were characterized by nonfluent speech, executive dysfunction, and dysarthria without apraxia of speech or frank agrammatism. No baseline clinical features differentiated between FTLD neuropathological subgroups. The Hopkins statistic demonstrated a low cluster tendency in the entire sample (.45 with values near 0.5 indicating random data). Cluster stability analyses showed that only two robust subgroups (differing in agrammatism, executive dysfunction and overall disease severity) could be identified. Three data-driven components accounted for 71% of the variance ([i] severity-agrammatism, [ii] prominent AOS, and [iii] prominent dysarthria). None of these data-driven LCD allowed an accurate prediction of neuropathology. The severity-agrammatism component was an independent predictor of a faster CDR-SB increase in all the participants. Higher dysarthria severity, reduced words per minute, and expressive and receptive agrammatism severity at baseline independently predicted accelerated disease progression. Our findings indicate that PPAOS and PAA, rather than exist as completely distinct syndromic entities, constitute a clinical continuum. In our cohort, splitting the nfvPPA spectrum into separate clinical phenotypes did not improve clinical-pathological correlations, stressing the need for new biological markers and consensus regarding updated terminology and clinical classification.

The development of the Cognitive Assessment for Tagalog Speakers (CATS): A culturally and linguistically tailored test battery for Filipino Americans.

INTRODUCTION: Filipino Americans are one of the largest Asian American and Pacific Islander (AAPI) populations in the United States (US). Previous studies suggest that Filipino Americans have one of the highest incidence rates of Alzheimer's disease and related dementias (ADRD) among AAPI subgroups. Despite the expected increase in Filipino Americans with ADRD, no studies to-date have validated neuropsychological measures in the United States for speakers of Tagalog, a major language spoken by Filipino Americans. A significant barrier to dementia care and diagnosis is the lack of linguistically and socioculturally appropriate cognitive tasks for Tagalog speakers. To address this need, we developed and piloted the Cognitive Assessment for Tagalog Speakers (CATS), the first neuropsychological battery for the detection of ADRD in Filipino American Tagalog speakers. METHODS: Based on evidence-based neuropsychological batteries, we adapted and constructed de novo tasks to measure performance across 4 main cognitive domains: visual/verbal memory, visuospatial functioning, speech and language, and frontal/executive functioning. Tasks were developed with a team of bilingual English/Tagalog, bicultural Filipino American/Canadian experts, including a neurologist, speech-language pathologist, linguist, and neuropsychologist. We recruited Tagalog-speaking participants of age 50+ through social media advertisements and recruitment registries for this cross-sectional study. We present the CATS design and protocol. RESULTS: To-date, the CATS battery has been administered to 26 healthy control participants (age 64.5 ± 7.8 years, 18F/8 M) at an academic institution in Northern California, United States. The development and administration of the CATS battery demonstrated its feasibility but also highlighted the need to consider the effects of bilingualism, language typology, and cultural factors in result interpretation. DISCUSSION: The CATS battery provides a mechanism for cognitive assessment of Filipino Americans, a population that has been underrepresented in ADRD research. As we move toward the treatment and cure of ADRD, linguistically and socioculturally appropriate cognitive tests become even more important for equitable care.

Speech and language markers of neurodegeneration: a call for global equity.

In the field of neurodegeneration, speech and language assessments are useful for diagnosing aphasic syndromes and for characterizing other disorders. As a complement to classic tests, scalable and low-cost digital tools can capture relevant anomalies automatically, potentially supporting the quest for globally equitable markers of brain health. However, this promise remains unfulfilled due to limited linguistic diversity in scientific works and clinical instruments. Here we argue for cross-linguistic research as a core strategy to counter this problem. First, we survey the contributions of linguistic assessments in the study of primary progressive aphasia and the three most prevalent neurodegenerative disorders worldwide-Alzheimer's disease, Parkinson's disease, and behavioural variant frontotemporal dementia. Second, we address two forms of linguistic unfairness in the literature: the neglect of most of the world's 7000 languages and the preponderance of English-speaking cohorts. Third, we review studies showing that linguistic dysfunctions in a given disorder may vary depending on the patient's language and that English speakers offer a suboptimal benchmark for other language groups. Finally, we highlight different approaches, tools and initiatives for cross-linguistic research, identifying core challenges for their deployment. Overall, we seek to inspire timely actions to counter a looming source of inequity in behavioural neurology.

Network anatomy in logopenic variant of primary progressive aphasia.

The logopenic variant of primary progressive aphasia (lvPPA) is a neurodegenerative syndrome characterized linguistically by gradual loss of repetition and naming skills, resulting from left posterior temporal and inferior parietal atrophy. Here, we sought to identify which specific cortical loci are initially targeted by the disease (epicenters) and investigate whether atrophy spreads through pre-determined networks. First, we used cross-sectional structural MRI data from individuals with lvPPA to define putative disease epicenters using a surface-based approach paired with an anatomically-fine-grained parcellation of the cortical surface (i.e., HCP-MMP1.0 atlas). Second, we combined cross-sectional functional MRI data from healthy controls and longitudinal structural MRI data from individuals with lvPPA to derive the epicenter-seeded resting-state networks most relevant to lvPPA symptomatology and ascertain whether functional connectivity in these networks predicts longitudinal atrophy spread in lvPPA. Our results show that two partially distinct brain networks anchored to the left anterior angular and posterior superior temporal gyri epicenters were preferentially associated with sentence repetition and naming skills in lvPPA. Critically, the strength of connectivity within these two networks in the neurologically-intact brain significantly predicted longitudinal atrophy progression in lvPPA. Taken together, our findings indicate that atrophy progression in lvPPA, starting from inferior parietal and temporo-parietal junction regions, predominantly follows at least two partially non-overlapping pathways, which may influence the heterogeneity in clinical presentation and prognosis.

Network anatomy in logopenic variant of primary progressive aphasia.

The logopenic variant of primary progressive aphasia (lvPPA) is a neurodegenerative syndrome characterized linguistically by gradual loss of repetition and naming skills resulting from left posterior temporal and inferior parietal atrophy. Here, we sought to identify which specific cortical loci are initially targeted by the disease (epicenters) and investigate whether atrophy spreads through predetermined networks. First, we used cross-sectional structural MRI data from individuals with lvPPA to define putative disease epicenters using a surface-based approach paired with an anatomically fine-grained parcellation of the cortical surface (i.e., HCP-MMP1.0 atlas). Second, we combined cross-sectional functional MRI data from healthy controls and longitudinal structural MRI data from individuals with lvPPA to derive the epicenter-seeded resting-state networks most relevant to lvPPA symptomatology and ascertain whether functional connectivity in these networks predicts longitudinal atrophy spread in lvPPA. Our results show that two partially distinct brain networks anchored to the left anterior angular and posterior superior temporal gyri epicenters were preferentially associated with sentence repetition and naming skills in lvPPA. Critically, the strength of connectivity within these two networks in the neurologically-intact brain significantly predicted longitudinal atrophy progression in lvPPA. Taken together, our findings indicate that atrophy progression in lvPPA, starting from inferior parietal and temporoparietal junction regions, predominantly follows at least two partially nonoverlapping pathways, which may influence the heterogeneity in clinical presentation and prognosis.

Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities-focused research.

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice.

Assessing the role of collectivism and individualism on COVID-19 beliefs and behaviors in the Southeastern United States.

America's unique response to the global COVID-19 pandemic has been both criticized and applauded across political and social spectrums. Compared to other developed nations, U.S. incidence and mortality rates were exceptionally high, due in part to inconsistent policies across local, state, and federal agencies regarding preventive behaviors like mask wearing and social distancing. Furthermore, vaccine hesitancy and conspiracy theories around COVID-19 and vaccine safety have proliferated widely, making herd immunity that much more challenging. What factors of the U.S. culture have contributed to the significant impact of the pandemic? Why have we not responded better to the challenges of COVID-19? Or would many people in the U.S. claim that we have responded perfectly well? To explore these questions, we conducted a qualitative and quantitative study of Florida State University faculty, staff, and students. This study measured their perceptions of the pandemic, their behaviors tied to safety and community, and how these practices were tied to beliefs of individualism and collectivism. We found that collectivist orientations were associated with a greater likelihood of wearing masks consistently, severe interruptions of one's social life caused by the pandemic, greater concern for infecting others, and higher levels of trust in medical professionals for behavioral guidelines surrounding the pandemic. These associations largely persist even after adjusting for political affiliation, which we find is also a strong predictor of COVID-19 beliefs and behaviors.

Food insecurity among university students in the United States amidst the COVID-19 pandemic.

OBJECTIVE: This study reports on food insecurity (FI) amidst the COVID-19 pandemic. PARTICIPANTS AND METHODS: College students in four regions of the US completed the two-item validated Hunger Vital Sign™ screening tool on Qualtrics. RESULTS: FI increased significantly after March 2020 among US students (worry about food running out: 25% to 35%; food did not last: 17% to 21%) with significant regional increase in the Midwest and South. An adjusted multivariable logistic regression model indicated students that ran out of food were significantly at greater odds of experiencing hardship with paying bills (AOR: 5.59, 95% CI =3.90-8.06). CONCLUSIONS: The findings identified an increase in the prevalence of FI among college students during the pandemic. Suggestions of how to address FI are discussed.

Barriers and Facilitators to the Collection and Aggregation of Electronic Health Record HIV Data: An Analysis of Study Recruitment Venues Within the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN).

Electronic health record (EHR) data can be leveraged for prospective cohort studies and pragmatic clinical trials, targeting youth living with HIV (YLH). Using EHRs in this manner may minimize the need for costly research infrastructure in service to lowering disease burden. This study characterizes HIV prevention and care continua variables and identifies factors likely to impede or facilitate EHR use for research and interventions. We conducted telephone-based qualitative interviews with National Experts (n = 10) and Key Stakeholders (n = 19) from subject recruitment venues (SRVs), providing care services to YLH and youth at risk for HIV. We found 17 different EHR systems being used for various purposes (e.g., workflow management and billing). Thematic content analysis of interviews highlighted six broad categories of perspectives on barriers to and facilitators of EHR use: specific variable collection, general use barriers, and facilitators, general data collection barriers and facilitators, EHRs for surveillance and research, EHRs for personnel and resource management and capture of HIV specific variables. These findings may inform implementation strategies of future studies, in which we conduct routine monitoring of the youth HIV prevention and care continua using EHRs and test an eHealth intervention.

Teaching About Racism in Medical Education: A Mixed-Method Analysis of a Train-the-Trainer Faculty Development Workshop.

BACKGROUND AND OBJECTIVES: Curriculum addressing racism as a driver of inequities is lacking at most health professional programs. We describe and evaluate a faculty development workshop on teaching about racism to facilitate curriculum development at home institutions. METHODS: Following development of a curricular toolkit, a train-the-trainer workshop was delivered at the 2017 Society of Teachers of Family Medicine Annual Spring Conference. Preconference evaluation and a needs assessment collected demographic data of participants, their learning communities, and experience in teaching about racism. Post-conference evaluations were completed at 2- and 6-month intervals querying participants' experiences with teaching about racism, including barriers; commitment to change expressed at the workshop; and development of the workshop-delivered curriculum. We analyzed quantitative data using Statistical Package for the Social Sciences (SPSS) software and qualitative data, through open thematic coding and content analysis. RESULTS: Forty-nine people consented to participate. The needs assessment revealed anxiety but also an interest in obtaining skills to teach about racism. The most reported barriers to developing curriculum were institutional and educator related. The majority of respondents at 2 months (61%, n=14/23) and 6 months (70%, n=14/20) had used the toolkit. Respondents ranked all 10 components as useful. The three highest-ranked components were (1) definitions and developing common language; (2) facilitation training, exploring implicit bias, privilege, intersectionality and microaggressions, and videos/podcasts; and (3) Theater of the Oppressed and articles/books. CONCLUSIONS: Faculty development training, such as this day-long workshop and accompanying toolkit, can advance skills and increase confidence in teaching about racism.

Optimizing Precision of Hypertension Care to Maximize Blood Pressure Control: A Pilot Study Utilizing a Smartphone App to Incorporate Plasma Renin Activity Testing.

Only half of patients with hypertension (HTN) respond to any given antihypertensive medication. Heterogeneity in pathophysiologic pathways underlying HTN is a major contributor. Personalizing antihypertensive therapy could improve blood pressure (BP) reduction. The objective of this study was to assess the effect of pragmatic implementation of a personalized plasma renin activity (PRA)-based smartphone app on improving BP reduction. Patients with untreated or treated but uncontrolled HTN were recruited. BP and PRA were measured at baseline with final BP measured at 6 months. Patient's information was entered into the app and treatment recommendations were returned. Clinicians were at liberty to follow or disregard the app's recommendations. BP levels and percent BP control among patients whose clinicians did and did not follow the app's recommendations were compared using independent t-test and Fisher's exact test, respectively. Twenty-nine European American patients were included (38% women) with mean age of 52 ± 9 years and median PRA of 1.3 ng/mL/hr (interquartile range 0.5-3.1 ng/mL/hr). Participants whose clinicians followed the app's recommendations (n = 16, 55%) as compared with those whose clinicians did not (n = 13, 45%), had a greater reduction in 6-month systolic BP (-15 ± 21 vs. -3 ± 21 mm Hg; adjusted-P = 0.1) and diastolic BP (-8 ± 8 vs. -1 ± 8 mm Hg; adjusted-P = 0.04). BP control at 6 months tended to be greater among patients whose clinicians accepted the app's recommendations vs. those whose clinicians did not (63% vs. 23%, P = 0.06). This pilot study demonstrates that acceptance of the app's recommendations was associated with a greater BP reduction. Future studies to confirm these pilot findings are warranted.

Effects of bilingualism on age at onset in two clinical Alzheimer's disease variants.

INTRODUCTION: The effect of bilingualism on age at onset has yet to be examined within different clinical variants of Alzheimer's disease. METHODS: We reviewed the research charts of 287 well-characterized participants with either amnestic Alzheimer's dementia or logopenic variant primary progressive aphasia (lvPPA) and identified bilingual speakers based on regular use of two or more languages and/or ability to communicate with native speakers in two or more languages. We evaluated whether bilingual speakers demonstrated a delay in age of symptom onset relative to monolingual speakers while controlling for other variables known to influence cognitive reserve. RESULTS: A 5-year delay in age at symptom onset was observed for bilingual relative to monolingual speakers with lvPPA. This delay in onset was not observed in the amnestic Alzheimer's dementia cohort. DISCUSSION: Bilingualism may serve as a unique cognitive reserve variable in lvPPA, but not in amnestic Alzheimer's dementia.

Atypical clinical features associated with mixed pathology in a case of non-fluent variant primary progressive aphasia.

A 66-year-old woman presented with agrammatism and apraxia of speech, meeting criteria for non-fluent/agrammatic variant primary progressive aphasia (nfvPPA). However, three years later, she developed frontal/executive, short-term phonological memory, visuospatial, and visual memory deficits suggesting involvement of multiple brain networks. Multimodal neuroimaging showed damage of both fronto-striatal and posterior brain regions. She was found to have multiple pathological processes: corticobasal degeneration (CBD), Alzheimer's disease (AD), and TAR DNA-binding protein (TDP)-43 type A. We hypothesize that cognitive and neuroimaging findings consistent with damage to multiple brain networks, each associated with vulnerability to certain molecular disease subtypes, could indicate mixed pathology.

Adaptación cultural al español y baremación del Adolescent Peer Relations Instrument (APRI) para la detección de la victimización por acoso escolar: Estudio preliminar de las propiedades psicométricas / Cultural adaptation to Spanish and assessment of an Adolescent Peer Relationships Tool for detecting school bullying: Preliminary study of the psychometric properties

Fundamentos y objetivos: El acoso escolar es un problema de magnitud creciente para el que existen escasos instrumentos breves validados al español. El objetivo de este estudio es adaptar y validar una escala breve de medición del bullying. Material y métodos: Se realizó una adaptación transcultural, mediante la técnica de traducción-retrotraducción, de la escala Adolescent Peer Relations Instrument-Bullying (APRI). La versión adaptada al español del cuestionario APRI se administró a una muestra de 1.428 escolares de entre 12-14años de la comarca del Mar Menor de Murcia (España). Se utilizó el análisis factorial exploratorio, con rotación oblicua, para evaluar la validez de la estructura interna, el alfa de Cronbach para analizar su consistencia y el test de Kruskal-Wallis para comprobar su capacidad de discriminación entre sujetos con distintos grados de bullying según la escala Kidscreen-52 de aceptabilidad social. Resultados: En la versión adaptada del APRI se identificaron 2 factores (victimización física y victimización verbal/social) similares a los de la escala original. El cuestionario tiene una elevada consistencia interna (alfa de Cronbach=0,94) y capacidad de discriminación (p<0,01), con tamaños de efecto considerables entre los distintos grupos de grado de bullying. Conclusiones: La estructura interna de versión en español del APRI es análoga a la original, y sus puntuaciones confirman una elevada fiabilidad y validez de constructo. Serán necesarios estudios posteriores, con rangos de edad más amplios y técnicas de análisis confirmatorio, para ratificar la equivalencia de la versión adaptada con la original (AU)

Background and objectives: School bullying is a growing problem. The current study is aimed at culturally adapting and assessing the psychometric properties of a brief scale to measure bullying. Material and methods: A cross-cultural adaptation of the brief scale —Adolescent Peer Relations Instrument-Bullying (APRI)— was performed using the translation and back-translation technique. The Spanish version of APRI questionnaire was administered to a sample of 1,428 schoolchildren aged 12-14years in the region of Mar Menor in Murcia (Spain). Exploratory factor analysis, with oblique rotation, was used to assess the validity of the internal structure, the Cronbach's alpha to analyse their consistency, and the Kruskal-Wallis test to check their ability to discriminate between subjects with varying degrees of bullying according to Kidscreen-52 scale of social acceptability. Results: Two factors were identified in the adapted version of APRI (physical victimisation and verbal/social victimisation), similar to those in the original scale. The questionnaire has high internal consistency (Cronbach's alpha=0.94) and discrimination capacity (P<01), with significant effect sizes between degrees of bullying. Conclusions: The internal structure of the APRI Spanish version is similar to the original, and its scores confirm high reliability and construct validity. Further studies need to be performed with broader age ranges and confirmatory analysis techniques, to ratify the equivalence of the adapted version with the original version (AU)

Engaging African American women in research: an approach to eliminate health disparities in the African American community.

Objective: To explore the success of community-based participatory research [CBPR] in engaging African American women to achieve health equity by elucidating community, trust, communication and impact. Recommendations helpful for researchers interested in engaging communities to achieve health equity in the USA are included. Inroduction: African American women experience health disparities of multifactorial etiology and are underrepresented in research. CBPR is a collaborative approach that incorporates perspectives, which address the intricate determinants of health and has been reported as an effective means to address health disparities. Yet, the science of CBPR seems elusive to researchers in the medical field. The opportunity exists to better understand and expand the use of the principles of engagement, replication, and sustainability in engaging African American women in health research. Methods: A variety of literature regarding engaging African American women in community-based participatory research was reviewed. Results: CBPR focused on robust engagement of marginalized groups continues to be validated as a vital approach to the elimination of disparities and improved health for all, especially ethnic and racial minority populations. However, limited evidence of focused engagement of African American women was found. Making specific outreach to African American women must be a community and patient engagement priority to achieve health equity. Conclusions: Continued research is needed which specifically focuses on building and sustaining engagement with African American women and their communities. This research can transform healthcare access, experiences and outcomes by yielding actionable information about what African American women need and want to promote wellness for themselves and their communities.

[Cultural adaptation to Spanish and assessment of an Adolescent Peer Relationships Tool for detecting school bullying: Preliminary study of the psychometric properties]. / Adaptación cultural al español y baremación del Adolescent Peer Relations Instrument (APRI) para la detección de la victimización por acoso escolar: Estudio preliminar de las propiedades psicométricas.

BACKGROUND AND OBJECTIVES: School bullying is a growing problem. The current study is aimed at culturally adapting and assessing the psychometric properties of a brief scale to measure bullying. MATERIAL AND METHODS: A cross-cultural adaptation of the brief scale -Adolescent Peer Relations Instrument-Bullying (APRI)- was performed using the translation and back-translation technique. The Spanish version of APRI questionnaire was administered to a sample of 1,428 schoolchildren aged 12-14years in the region of Mar Menor in Murcia (Spain). Exploratory factor analysis, with oblique rotation, was used to assess the validity of the internal structure, the Cronbach's alpha to analyse their consistency, and the Kruskal-Wallis test to check their ability to discriminate between subjects with varying degrees of bullying according to Kidscreen-52 scale of social acceptability RESULTS: Two factors were identified in the adapted version of APRI (physical victimisation and verbal/social victimisation), similar to those in the original scale. The questionnaire has high internal consistency (Cronbach's alpha=0.94) and discrimination capacity (P<01), with significant effect sizes between degrees of bullying. CONCLUSIONS: The internal structure of the APRI Spanish version is similar to the original, and its scores confirm high reliability and construct validity. Further studies need to be performed with broader age ranges and confirmatory analysis techniques, to ratify the equivalence of the adapted version with the original version.

Improving Adolescent Health Risk Assessment: A Multi-method Pilot Study.

Objectives Given poor compliance by providers with adolescent health risk assessment (HRA) in primary care, we describe the development and feasibility of using a health information technology (HIT)-enhanced HRA to improve the frequency of HRAs in diverse clinical settings, asking adolescents' recall of quality of care as a primary outcome. Methods We conducted focus groups and surveys with key stakeholders (Phase I) , including adolescents, clinic staff and providers to design and implement an intervention in a practice-based research network delivering private, comprehensive HRAs via tablet (Phase II). Providers and adolescents received geo-coded community resources according to individualized risks. Following the point-of-care implementation , we collected patient-reported outcomes using post-visit quality surveys (Phase III). Patient-reported outcomes from intervention and comparison clinics were analyzed using a mixed-model, fitted separately for each survey domain. Results Stakeholders agreed upon an HIT-enhanced HRA (Phase I). Twenty-two academic and community practices in north-central Florida then recruited 609 diverse adolescents (14-18 years) during primary care visits over 6 months; (mean patients enrolled = 28; median = 20; range 1-116; Phase II). Adolescents receiving the intervention later reported higher receipt of confidential/private care and counseling related to emotions and relationships (adjusted scores 0.42 vs 0.08 out of 1.0, p < .01; 0.85 vs 0.57, p < .001, respectively, Phase III) than those receiving usual care. Both are important quality indicators for adolescent well-child visits. Conclusions Stakeholder input was critical to the acceptability of the HIT-enhanced HRA. Patient recruitment data indicate that the intervention was feasible in a variety of clinical settings and the pilot evaluation data indicate that the intervention may improve adolescents' perceptions of high quality care.

A SAS-6-like protein suggests that the Toxoplasma conoid complex evolved from flagellar components.

SAS-6 is required for centriole biogenesis in diverse eukaryotes. Here, we describe a novel family of SAS-6-like (SAS6L) proteins that share an N-terminal domain with SAS-6 but lack coiled-coil tails. SAS6L proteins are found in a subset of eukaryotes that contain SAS-6, including diverse protozoa and green algae. In the apicomplexan parasite Toxoplasma gondii, SAS-6 localizes to the centriole but SAS6L is found above the conoid, an enigmatic tubulin-containing structure found at the apex of a subset of alveolate organisms. Loss of SAS6L causes reduced fitness in Toxoplasma. The Trypanosoma brucei homolog of SAS6L localizes to the basal-plate region, the site in the axoneme where the central-pair microtubules are nucleated. When endogenous SAS6L is overexpressed in Toxoplasma tachyzoites or Trypanosoma trypomastigotes, it forms prominent filaments that extend through the cell cytoplasm, indicating that it retains a capacity to form higher-order structures despite lacking a coiled-coil domain. We conclude that although SAS6L proteins share a conserved domain with SAS-6, they are a functionally distinct family that predates the last common ancestor of eukaryotes. Moreover, the distinct localization of the SAS6L protein in Trypanosoma and Toxoplasma adds weight to the hypothesis that the conoid complex evolved from flagellar components.

Cell division in Apicomplexan parasites is organized by a homolog of the striated rootlet fiber of algal flagella.

Apicomplexa are intracellular parasites that cause important human diseases including malaria and toxoplasmosis. During host cell infection new parasites are formed through a budding process that parcels out nuclei and organelles into multiple daughters. Budding is remarkably flexible in output and can produce two to thousands of progeny cells. How genomes and daughters are counted and coordinated is unknown. Apicomplexa evolved from single celled flagellated algae, but with the exception of the gametes, lack flagella. Here we demonstrate that a structure that in the algal ancestor served as the rootlet of the flagellar basal bodies is required for parasite cell division. Parasite striated fiber assemblins (SFA) polymerize into a dynamic fiber that emerges from the centrosomes immediately after their duplication. The fiber grows in a polarized fashion and daughter cells form at its distal tip. As the daughter cell is further elaborated it remains physically tethered at its apical end, the conoid and polar ring. Genetic experiments in Toxoplasma gondii demonstrate two essential components of the fiber, TgSFA2 and 3. In the absence of either of these proteins cytokinesis is blocked at its earliest point, the initiation of the daughter microtubule organizing center (MTOC). Mitosis remains unimpeded and mutant cells accumulate numerous nuclei but fail to form daughter cells. The SFA fiber provides a robust spatial and temporal organizer of parasite cell division, a process that appears hard-wired to the centrosome by multiple tethers. Our findings have broader evolutionary implications. We propose that Apicomplexa abandoned flagella for most stages yet retained the organizing principle of the flagellar MTOC. Instead of ensuring appropriate numbers of flagella, the system now positions the apical invasion complexes. This suggests that elements of the invasion apparatus may be derived from flagella or flagellum associated structures.

Memory Awareness Influences Everyday Decision Making Capacity about Medication Management in Alzheimer's Disease.

Memory awareness in early Alzheimer's disease (AD) influences capacity to provide informed consent for a memory treatment. This study investigated the extent to which aspects of memory awareness influence everyday decision-making capacity about medication management in AD. 42 participants with mild AD and 50 healthy elders underwent clinical ratings of memory awareness, metamemory testing, and an interview of everyday decision-making capacity regarding medication management. 45% of AD subjects were classified as aware (AAD) and 55% as unaware (UAD) based on clinical ratings and supported by metamemory testing (P = .015). Capacity was impaired in each of the AD groups as compared to the healthy elders F(2, 67) = 17.63, UAD, P < .01; AAD, P = .01). Within the AD group, capacity correlated selectively with awareness as measured with clinical ratings (r = -.41, P = .007) but not objective metamemory testing (r = -.10, P = .60 ). Appreciation scores were lower in UAD as compared with AAD F(1,35) = 8.36, P = .007. Unawareness of memory loss should heighten clinicians' concern about everyday decision-making capacity in AD.