Search

Current literature on the effect of cannabis use on sleep quality is mixed, and few studies have used objectively-measured sleep measures or real-time sampling of cannabis use to examine this relationship. The prevalence of cannabis use among older adults and persons living with HIV has increased in recent years, and poor sleep quality is elevated in these populations as well. However, research examining cannabis-sleep relationships in these populations is lacking. Thus, we aimed to examine the relationship between daily cannabis use and subsequent objectively-measured sleep quality in middle-aged and older adults with and without HIV. In this pilot study, seventeen (11 HIV+, 6 HIV-) adults aged 50-70 who consumed cannabis completed four daily smartphone-based surveys for 14 days, in which they reported their cannabis use (yes/no) since the last survey. Participants also wore actigraphy watches during the 14-day period to objectively assess sleep quality (i.e., efficiency, total sleep time, and sleep fragmentation). In linear mixed-effects models, cannabis use was significantly associated with greater subsequent total sleep time (β=0.56; p=0.046). Cannabis use was not related to a change in sleep efficiency (β=1.50; p=0.46) nor sleep fragmentation (β=0.846, p=0.756) on days with cannabis use versus days without cannabis use. These preliminary results indicate cannabis use may have a positive effect on sleep duration in middle-aged and older adults. However, future studies with larger sample sizes that assess cannabis use in more detail (e.g., route of administration, dose, reason for use) are needed to further understand this relationship.

BackgroundFive-year survival on dialysis is only 40%, compared to 74% with a deceased donor kidney transplant (DDKT) and 87% with a living donor kidney transplant (LDKT). An American Society of Transplantation (AST) Consensus Conference recommended that patients with chronic kidney disease (CKD) Stages 3-5 have the opportunity to learn about and decide which treatment option is right for them, particularly about LDKT. However, early education about LDKT and DDKT outside of transplant centers is inconsistent and often poor, with patients in CKD 3 and 4 and ethnic/racial minorities even less likely to receive it. A new randomized control trial (RCT), in partnership with Kaiser Permanente Southern California (KPSC), will assess knowledge gaps and the effectiveness of a supplementary video-guided, print and technology-based education intervention for English- and Spanish-speaking patients in CKD Stages 3, 4, and 5 to increase LDKT knowledge and decision-making. To date, no published LDKT educational interventions have studied such a large and diverse CKD population.MethodsIn this RCT, 1200 English and Spanish-speaking CKD Stage 3-5 patients will be randomly assigned to one of two education conditions: ET@Home or KPSC standard of care education. Randomization will be stratified by CKD stage and primary language spoken. Those in the ET@Home condition will receive brochures, postcards, DVDs, and text messages delivering educational content in modules over a six-month period. Baseline data collection will measure demographics, transplant derailers, and the amount of previous CKD and transplant education they have received. Changes in CKD and transplant knowledge, ability to make an informed decision about transplant, and self-efficacy to pursue LDKT will be captured with surveys administered at baseline and at six months.DiscussionAt the conclusion of the study, investigators will understand key knowledge gaps for patients along the CKD continuum and between patients who speak different languages and have assessed the effectiveness of both English- and Spanish-language supplementary education in increasing KPSC patients' knowledge about the opportunities for and risks and benefits of LDKT. We hope this program will reduce disparities in access to transplant.Trial registrationClinicalTrials.gov Identifier: NCT03389932; date registered: 12/26/2017.

BackgroundA personalized mobile health intervention (iSTEP) aims to promote a Mediterranean diet and increase physical activity, thereby improving neurocognitive functioning among persons living with HIV (PLWH). This article describes a qualitative study conducted to develop iSTEP for PLWH, including assessment of diet habits and preferences for tracking physical activity.MethodTwo focus groups, with seven and 13 PLWH respectively, discussed barriers and facilitators of a healthy diet and provided feedback to refine iSTEP components, including the feasibility of using a Fitbit and the content of text messages designed to encourage improved diet and physical activity.ResultsFocus group discussions revealed several healthy diet barriers, including housing instability, time required for food preparation, cost of healthy food, depression, gastrointestinal issues, physical disability, and changes in appetite since HIV diagnosis. Participant-identified healthy diet facilitators included affordable price options for healthy food, a structured food plan, desire to modify appearance or weight, access to medical professionals, motivation for disease prevention, and social support. Participants endorsed wearing a Fitbit on the wrist and receiving text messages as useful methods to monitor and encourage a better diet and greater physical activity.ConclusionsThese findings assisted the expansion of a mobile health intervention that promotes health behaviors in order to improve neurocognitive outcomes among PLWH.Trial registrationNCT03123731 , prospectively registered on ClinicalTrials.gov, April 21, 2017.

We report the first measurements with sub-kiloparsec spatial resolution of strongly inverted gas-phase metallicity gradients in two dwarf galaxies at z ∼ 2. The galaxies have stellar masses ∼109 , specific star formation rate ∼20 Gyr-1, and global metallicity (1/4 solar), assuming the strong-line calibrations of [O iii]/Hβ and [O ii]/Hβ from Maiolino et al. Their radial metallicity gradients are measured to be highly inverted, i.e., 0.122 ± 0.008 and 0.111 ± 0.017 dex kpc-1, which is hitherto unseen at such small masses in similar redshift ranges. From the Hubble Space Telescope observations of the source nebular emission and stellar continuum, we present two-dimensional spatial maps of star formation rate surface density, stellar population age, and gas fraction, which show that our galaxies are currently undergoing rapid mass assembly via disk inside-out growth. More importantly, using a simple chemical evolution model, we find that the gas fractions for different metallicity regions cannot be explained by pure gas accretion. Our spatially resolved analysis based on a more advanced gas regulator model results in a spatial map of net gaseous outflows, triggered by active central starbursts, that potentially play a significant role in shaping the spatial distribution of metallicity by effectively transporting stellar nucleosynthesis yields outwards. The relation between wind mass loading factors and stellar surface densities measured in different regions of our galaxies shows that a single type of wind mechanism, driven by either energy or momentum conservation, cannot explain the entire galaxy. These sources present a unique constraint on the effects of gas flows on the early phase of disk growth from the perspective of spatially resolved chemical evolution within individual systems.

Purpose Recent studies confirm the utility of speech-language intervention in primary progressive aphasia (PPA); however, long-term outcomes, ideal dosage parameters, and relative benefits of intervention across clinical variants warrant additional investigation. The purpose of this study was to determine whether naming treatment affords significant, lasting, and generalized improvement for individuals with semantic and logopenic PPA and whether dosage manipulations significantly affect treatment outcomes. Method Eighteen individuals with PPA (9 semantic and 9 logopenic variant) underwent lexical retrieval treatment designed to leverage spared cognitive-linguistic domains and develop self-cueing strategies to promote naming. One group (n = 10) underwent once-weekly treatment sessions, and the other group (n = 8) received the same treatment with 2 sessions per week and an additional "booster" treatment phase at 3 months post-treatment. Performance on trained and untrained targets/tasks was measured immediately after treatment and at 3, 6, and 12 months post-treatment. Results Outcomes from the full cohort of individuals with PPA showed significantly improved naming of trained items immediately post-treatment and at all follow-up assessments through 1 year. Generalized improvement on untrained items was significant up to 6 months post-treatment. The positive response to treatment was comparable regardless of session frequency or inclusion of a booster phase. Outcomes were comparable across PPA subtypes, as was maintenance of gains over the post-treatment period. Conclusion This study documents positive naming treatment outcomes for a group of individuals with PPA, demonstrating strong direct treatment effects, maintenance of gains up to 1 year post-treatment, and generalization to untrained items. Lexical retrieval treatment, in conjunction with daily home practice, had a strong positive effect that did not require more than 1 clinician-directed treatment session per week. Findings confirm that strategic training designed to capitalize on spared cognitive-linguistic abilities results in significant and lasting improvement, despite ongoing disease progression, in PPA.

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.

BackgroundImmune-mediated myositis (IMM) in American Quarter Horses (QHs) causes acute muscle atrophy and lymphocytic infiltration of myofibers. Recently, an E321G mutation in a highly conserved region of the myosin heavy chain 1 (MYH1) gene was associated with susceptibility to IMM and nonexertional rhabdomyolysis.ObjectivesTo estimate prevalence of the E321G MYH1 variant in the QH breed and performance subgroups.AnimalsThree-hundred seven elite performance QHs and 146 random registered QH controls.MethodsProspective genetic survey. Elite QHs from barrel racing, cutting, halter, racing, reining, Western Pleasure, and working cow disciplines and randomly selected registered QHs were genotyped for the E321G MYH1 variant and allele frequencies were calculated.ResultsThe E321G MYH1 variant allele frequency was 0.034 ± 0.011 in the general QH population (6.8% of individuals in the breed) and the highest among the reining (0.135 ± 0.040; 24.3% of reiners), working cow (0.085 ± 0.031), and halter (0.080 ± 0.027) performance subgroups. The E321G MYH1 variant was present in cutting (0.044 ± 0.022) and Western Pleasure (0.021 ± 0.015) QHs at lower frequency and was not observed in barrel racing or racing QHs.Conclusions and clinical importanceKnowing that reining and working cow QHs have the highest prevalence of the E321G MYH1 variant and that the variant is more prevalent than the alleles for hereditary equine regional dermal asthenia and hyperkalemic periodic paralysis in the general QH population will guide the use of genetic testing for diagnostic and breeding purposes.

Chronic kidney disease-associated pruritus (CKDaP) is an often under-diagnosed and under-recognized condition, despite its considerable prevalence within the chronic kidney disease (CKD) population. Universally accepted guidelines are also lacking. The true prevalence of CKDaP worldwide therefore remains unknown, although its negative impact on mortality and health-related quality of life outcomes is very clear. The pathophysiological mechanisms leading to the onset of CKDaP are only partly understood. CKDaP is currently believed to be caused by a multifactorial process, from local skin changes, metabolic alterations, the development of neuropathy and dysregulation of opioid pathways, and psychological factors. Much work has been carried out towards a more systematic and structured approach to clinical diagnosis. Various tools are now available to assess the severity of CKDaP. Many of these tools require greater validation before they can be incorporated into the guidelines and into routine clinical practice. Further efforts are also needed in order to increase the awareness of clinicians and patients so that they can identify the CKDaP signs and symptoms in a timely manner. Currently established treatment options for CKDaP focus on the prevention of xerosis via topical emollients, the optimization of dialysis management, early referral to kidney transplantation if appropriate, oral antihistamine, and a variety of neuropathic agents. Other novel treatment options include the following: topical analgesics, topical tacrolimus, cannabinoid-containing compounds, antidepressants, oral leukotrienes, opioids, and non-pharmacological alternative therapies (i.e., phototherapy, dietary supplements, acupuncture/acupressure). We provide an updated review on the evidence relating to the epidemiology, the pathophysiology, the clinical assessment and diagnosis, and the management of CKDaP.

Anemia in chronic kidney disease (CKD) has become an important clinical issue with the increased prevalence of elderly patients living with CKD progressing to kidney failure. The causes of anemia in elderly individuals tend to be multifactorial, exacerbated by the physiological effects of aging, frailty and declining kidney function. Erythropoiesis-stimulating agents (ESAs) are the conventional therapeutic option for anemia in CKD. However, ESA hyporesponsiveness is a commonly observed issue in clinical practice and an issue that is more challenging to resolve in elderly patients living with frailty, kidney disease, and multi-morbidities. Following the emergence of oral hypoxia-induced factor prolyl-hydroxylase inhibitors (HIF-PHI) in recent years, there is discussion on whether it is a solution to the conundrum of ESA hyporesponsiveness, as HIF-PHI treats anemia via an alternative physiological pathway. There remains uncertainty on the suitability of HIF-PHI use in elderly patients, given a lack of data on its safety over long-term follow-up for the elderly population. Further study is needed to provide answers, considering the clinical significance of this issue within a public-health scale.

Abstract This study aimed to evaluate the efficacy of 18-month 0.01% atropine in 61 myopic children (aged 7–10) and the relationship with central retinal response (by multifocal electroretinogram [mfERG]) in a double-masked randomized placebo-controlled clinical trial. Global-flash mfERG was measured at baseline, while cycloplegic spherical equivalent refraction (SER) and axial length (AL) were measured at baseline and at 6-month intervals. Annualized change in SER and AL were compared between atropine and control groups, and the relationships with baseline mfERG were evaluated. Changes in SER (−0.70 ± 0.39D vs. −0.66 ± 0.41D, p = 0.63) and AL (0.32 ± 0.16 mm vs. 0.30 ± 0.22 mm, p = 0.52) were similar in atropine and control groups. Interestingly, in the placebo group, mfERG amplitude was negatively correlated with axial elongation (Rp = −0.44, p = 0.03) as in our previous study. However, in the atropine group, an opposite trend was observed that axial elongation was positively correlated with mfERG amplitude (Ra = 0.37, p = 0.04). Annualized myopia progression demonstrated similar opposite effect between atropine and placebo groups but did not reach statistical significance. An ERG screening protocol may be warranted to identify suitable candidates to reduce the likelihood of an unfavorable treatment response by 0.01% atropine.

Acute lymphoblastic leukaemia is the most common childhood malignancy that remains a leading cause of death in childhood. It may be characterised by multiple known recurrent genetic aberrations that inform prognosis, the most common being hyperdiploidy and t(12;21) ETV6::RUNX1. We aimed to assess the applicability of a new imaging flow cytometry methodology that incorporates cell morphology, immunophenotype, and fluorescence in situ hybridisation (FISH) to identify aneuploidy of chromosomes 4 and 21 and the translocation ETV6::RUNX1. We evaluated this new "immuno-flowFISH" platform on 39 cases of paediatric ALL of B-lineage known to have aneuploidy of chromosomes 4 and 21 and the translocation ETV6::RUNX1. After identifying the leukaemic population based on immunophenotype (i.e., expression of CD34, CD10, and CD19 antigens), we assessed for copy numbers of loci for the centromeres of chromosomes 4 and 21 and the ETV6 and RUNX1 regions using fluorophore-labelled DNA probes in more than 1000 cells per sample. Trisomy 4 and 21, tetrasomy 21, and translocations of ETV6::RUNX1, as well as gains and losses of ETV6 and RUNX1, could all be identified based on FISH spot counts and digital imagery. There was variability in clonal makeup in individual cases, suggesting the presence of sub-clones. Copy number alterations and translocations could be detected even when the cell population comprised less than 1% of cells and included cells with a mature B-cell phenotype, i.e., CD19-positive, lacking CD34 and CD10. In this proof-of-principle study of 39 cases, this sensitive and specific semi-automated high-throughput imaging flow cytometric immuno-flowFISH method has been able to show that alterations in ploidy and ETV6::RUNX1 could be detected in the 39 cases of paediatric ALL. This imaging flow cytometric FISH method has potential applications for diagnosis and monitoring disease and marrow regeneration (i.e., distinguishing residual ALL from regenerating haematogones) following chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review explores the updates in the application of advanced cardiac imaging modalities, including cardiac computed tomography (CCT), cardiac magnetic resonance (CMR) imaging, and positron emission tomography (PET) in cardio-oncology. These imaging modalities have distinctive roles in baseline risk stratification, surveillance, and diagnosis of cardiotoxicity. Recent Findings: In recent years, there has been increased recognition of advanced imaging techniques in the field of cardio-oncology. With the advent of newer cancer therapeutics like immunotherapy, there has been a rise in cardiotoxicity related to these agents, including myocarditis, pericarditis, and accelerated atherosclerosis. CMR, in particular, is an essential noninvasive diagnostic test for these immunotherapy-related cardiotoxicities, albeit with diagnostic limitations depending on the disease presentation (Zhang et al. Eur Heart J. 41(18):1733-1743, 2020; Schwartz et al. Am J Med. 82(6):1109-18, 1987). Furthermore, CCT is often used in cardio-oncology patients to rule out CAD, with an expansion of its role in evaluating immune checkpoint inhibitor (ICI) myocarditis and for evaluating accelerated atherosclerosis in patients on ICI therapy (Suero-Abreu et al. JACC CardioOncol. 4(5):598-615, 2022). Coronary artery calcium (CAC) scoring on chest CT in cancer patients is a recommended risk stratification tool in addition to dedicated cardiac testing. At the same time, cardiac PET provides additional information in patients with cardiac masses. Functional testing using cardiac PET coronary flow reserve (CFR) is helpful in patients' baseline risk stratification and diagnosing microvascular disease. Summary: Cardio-oncology is a growing field with increased recognition of newer cardiotoxicities and the advent of more unique cancer treatments. Imaging techniques like echocardiogram and echocardiogram-derived global longitudinal strain (GLS) are the current workhorse for baseline risk stratification, surveillance, and cancer therapy-related cardiovascular toxicity (CTR-CVT) diagnosis. However, additional advanced cardiac imaging modalities play a unique role in risk stratification or surveillance in patients with suboptimal echocardiograms for various factors. Additionally, advanced cardiac imaging techniques are crucial in patients with abnormal echocardiograms or clinical presentations concerning for cardiotoxicity to confirm those findings or establish an accurate diagnosis—for example, CMR in ICI myocarditis or PET for cardiac masses. [ABSTRACT FROM AUTHOR]

Clostridioides difficile (C. difficile) is a bacterial organism that typically infects the colon, which has had its homeostasis of healthy gut microbiota disrupted by antibiotics or other interventions. Patients with kidney transplantation are a group that are susceptible to C. difficile infection (CDI) and have poorer outcomes with CDI given that they conventionally require long-term immunosuppression to minimize their risk of graft rejection, weakening their responses to infection. Recognizing the risk factors and complex pathophysiological processes that exist between immunosuppression, dysbiosis, and CDI is important when making crucial clinical decisions surrounding the management of this vulnerable patient cohort. Despite the clinical importance of this topic, there are few studies that have evaluated CDI in the context of kidney transplant recipients and other solid organ transplant populations. The current recommendations on CDI management in kidney transplant and solid organ transplant recipients are mostly extrapolated from data relating to CDI management in the general population. We provide a narrative review that discusses the available evidence examining CDI in solid organ transplant recipients, with a particular focus on the kidney transplant recipient, from the epidemiology of CDI, clinical features and implications of CDI, potential risk factors of CDI, and, ultimately, prevention and management strategies for CDI, with the aim of providing areas for future research development in this topic area.

INTRODUCTION After the release of the 2021 National Academies of Sciences, Engineering, and Medicine (NASEM) report on Implementing High-Quality Primary Care, a group L of early career primary care clinicians [...], The 2021 National Academies of Sciences, Engineering, and Medicine (NASEM) report on Implementing High-Quality Primary Care identifies 5 high-level objectives regarding payment, access, workforce development, information technology, and implementation. Nine junior primary care leaders (3 internal medicine, 3 family medicine, 3 pediatrics) invited from broad geographies, practice settings, and academic backgrounds used appreciative inquiry to identify priorities for the future of primary care. Highlighting the voices of these early career clinicians, we propose a response to the report from the perspective of early career primary care physicians. Health equity must be the foundation of the future of primary care. Because Barbara Starfield's original 4 Cs (first contact, coordination, comprehensiveness, and continuity) may not be inclusive of the needs of under-resourced communities, we promote an extension to include 5 additional Cs: convenience, cultural humility, structural competency, community engagement, and collaboration. We support the NASEM report's priorities and its focus on achieving health equity. We recommend investing in local communities and preparatory programs to stimulate diverse individuals to serve in health care. Finally, we support a blended value-based care model with risk adjustment for the social complexity of our patients. Ann Fam Med 2022;20:175-178. https://doi.org/10.1370/afm.2789 Appeared as Annals "Online First" article.

Objective: To understand whether symptoms of health conditions explain the negative association between combat exposure and student Veterans' achievement of a meaningful life. Participants: 153 combat Veterans enrolled in college between November 2013 and April 2018. Methods: Through an online survey, participants reported combat exposure, health status (symptoms of conditions such as depression), and aspects of a meaningful life (belonging, self-understanding, and doing) at two time points. Path analysis was used to explore whether baseline health status mediated the relationship between combat exposure and belonging, self-understanding, and doing at follow-up. Results: Indirect effects indicated that the negative influence of combat on student Veterans' sense of belonging, self-understanding, and doing at follow-up was mediated by poor health at baseline. Conclusions: Combat exposure may contribute to the development of health conditions, which in turn limit student Veterans' experience of three aspects of a meaningful life: a sense of belonging, self-understanding, and doing.

IntroductionPrimary progressive aphasia (PPA) is a neurodegenerative disorder characterized by progressive deterioration of speech and language. A growing body of research supports the utility of speech and language intervention in individuals with PPA, although access to these services remains limited. One potential means of increasing treatment accessibility is the delivery of treatment via telemedicine. Evidence supports the use of teletherapy in stroke-induced aphasia, but research examining the application of teletherapy in PPA is limited. In the current study, a non-randomized group comparison design was used to evaluate the feasibility and utility of treatment delivered via teletherapy relative to treatment administered in person for individuals with PPA.MethodsTwo treatment protocols were administered as part of a larger study investigating treatment for speech and language deficits in PPA. Participants with semantic (n=10) and logopenic (n=11) PPA received lexical retrieval treatment and individuals with nonfluent/agrammatic PPA (n=10) received video-implemented script training for aphasia designed to promote speech production and fluency. Treatment was administered via teletherapy for approximately half of the participants receiving each intervention. Treatment outcomes and performance on standardized tests were assessed at pre-treatment and post-treatment, as well as 3, 6, and 12 months post-treatment.ResultsOverall, both treatment approaches resulted in significant gains for primary outcome measures. Critically, comparison of in-person and teletherapy groups revealed comparable outcomes. Generalization to untrained targets and tasks and maintenance of treatment-induced gains were also comparable for traditional vs teletherapy participants.ConclusionOverall, treatment outcomes were largely equivalent for individuals receiving treatment via teletherapy vs traditional, in-person delivery. Results support the application of teletherapy for administering restitutive interventions to individuals with mild-to-moderate PPA. Potential implications for using teletherapy in the treatment of cognitive-linguistic and motoric impairments in other disorders and suggestions for administering treatment via telemedicine are discussed.

In the original publication, age stratified mortality rates were incorrectly added in Fig. 2. The correct Fig. 2 is given below.

Non-fluent/agrammatic primary progressive aphasia (nfvPPA) is caused by neurodegeneration within the left fronto-insular speech and language production network (SPN). Graph theory is a branch of mathematics that studies network architecture (topology) by quantifying features based on its elements (nodes and connections). This approach has been recently applied to neuroimaging data to explore the complex architecture of the brain connectome, though few studies have exploited this technique in PPA. Here, we used graph theory on functional MRI resting state data from a group of 20 nfvPPA patients and 20 matched controls to investigate topological changes in response to focal neurodegeneration. We hypothesized that changes in the network architecture would be specific to the affected SPN in nfvPPA, while preserved in the spared default mode network (DMN). Topological configuration was quantified by hub location and global network metrics. Our findings showed a less efficiently wired and less optimally clustered SPN, while no changes were detected in the DMN. The SPN in the nfvPPA group showed a loss of hubs in the left fronto-parietal-temporal area and new critical nodes in the anterior left inferior-frontal and right frontal regions. Behaviorally, speech production score and rule violation errors correlated with the strength of functional connectivity of the left (lost) and right (new) regions respectively. This study shows that focal neurodegeneration within the SPN in nfvPPA is associated with network-specific topological alterations, with the loss and gain of crucial hubs and decreased global efficiency that were better accounted for through functional rather than structural changes. These findings support the hypothesis of selective network vulnerability in nfvPPA and may offer biomarkers for future behavioral intervention.

BackgroundAn E321G mutation in MYH1 was recently identified in Quarter Horses (QH) with immune-mediated myositis (IMM) defined by a phenotype of gross muscle atrophy and myofiber lymphocytic infiltrates.Hypothesis/objectivesWe hypothesized that the MYH1 mutation also was associated with a phenotype of nonexertional rhabdomyolysis. The objective of this study was to determine the prevalence of the MYH1 mutation in QH with exertional (ER) and nonexertional (nonER) rhabdomyolysis.AnimalsQuarter Horses: 72 healthy controls, 85 ER-no atrophy, 56 ER-atrophy, 167 nonER horses selected regardless of muscle atrophy.MethodsClinical and histopathologic information and DNA was obtained from a database for (1) ER > 2 years of age, with or without atrophy and (2) nonER creatine kinase (CK) ≥ 5000 U/L,

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) presents with a gradual decline in grammar and motor speech resulting from selective degeneration of speech-language regions in the brain. There has been considerable progress in identifying treatment approaches to remediate language deficits in other primary progressive aphasia variants; however, interventions for the core deficits in nfvPPA have yet to be systematically investigated. Further, the neural mechanisms that support behavioural restitution in the context of neurodegeneration are not well understood. We examined the immediate and long-term benefits of video implemented script training for aphasia (VISTA) in 10 individuals with nfvPPA. The treatment approach involved repeated rehearsal of individualized scripts via structured treatment with a clinician as well as intensive home practice with an audiovisual model using 'speech entrainment'. We evaluated accuracy of script production as well as overall intelligibility and grammaticality for trained and untrained scripts. These measures and standardized test scores were collected at post-treatment and 3-, 6-, and 12-month follow-up visits. Treatment resulted in significant improvement in production of correct, intelligible scripted words for trained topics, a reduction in grammatical errors for trained topics, and an overall increase in intelligibility for trained as well as untrained topics at post-treatment. Follow-up testing revealed maintenance of gains for trained scripts up to 1 year post-treatment on the primary outcome measure. Performance on untrained scripts and standardized tests remained relatively stable during the follow-up period, indicating that treatment helped to stabilize speech and language despite disease progression. To identify neural predictors of responsiveness to intervention, we examined treatment effect sizes relative to grey matter volumes in regions of interest derived from a previously identified speech production network. Regions of significant atrophy within this network included bilateral inferior frontal cortices and supplementary motor area as well as left striatum. Volumes in a left middle/inferior temporal region of interest were significantly correlated with the magnitude of treatment effects. This region, which was relatively spared anatomically in nfvPPA patients, has been implicated in syntactic production as well as visuo-motor facilitation of speech. This is the first group study to document the benefits of behavioural intervention that targets both linguistic and motoric deficits in nfvPPA. Findings indicate that behavioural intervention may result in lasting and generalized improvement of communicative function in individuals with neurodegenerative disease and that the integrity of spared regions within the speech-language network may be an important predictor of treatment response.

PurposeThe early period after chronic kidney disease (CKD) patients transition to end-stage renal disease (ESRD) represents the highest mortality risk but is variable among different patient populations and clinical circumstances. We compared early mortality outcomes among a diverse CKD population that transitioned to ESRD.MethodsA retrospective cohort study (1/1/2002 through 12/31/2013) of CKD patients (age ≥ 18 years) who transitioned to peritoneal dialysis (PD), hemodialysis (HD) with arteriovenous fistula/grafts, and HD with catheters was performed. Multivariable Cox regression modeling was used to estimate 6-month all-cause mortality hazard ratios (HR) among the three treatment groups after adjustment for patient and clinical characteristics.ResultsAmong 5373 ESRD patients (62.7 years, 41.3% females, 37.5% Hispanics, 13.3% PD, 34.9% HD with fistula/graft, 51.8% HD with catheter), 551 (10.3%) died at 6 months. Mortality rates were highest immediately after transition (299 deaths per 1000 person-years in first month). Compared to PD patients, the 6-month mortality HR (95% CI) was 1.87 (1.06-3.30) in HD with fistula/graft patients and 3.77 (2.17-6.57) in HD with catheter patients. Inpatient transition (HR 1.32), acute kidney injury (HR 2.06), and an eGFR ≥ 15 vs 5-9 (HR 1.68) at transition were also associated with higher early mortality risk.ConclusionAmong a diverse CKD population who transitioned to ESRD, we observed considerable differences in early mortality risk among PD, HD with fistula/graft, and HD with catheter patients. The identification of patient-specific and clinical environmental factors related to high early mortality may provide insights for managing advanced stages of CKD and shared decision making.

Higher levels of physical activity (PA) have been linked to better neurocognitive functioning in many populations. The current study examines the longitudinal association between PA and neurocognitive functioning among HIV-infected and HIV-uninfected persons. Community-dwelling adults (N = 291) self-reported level of PA and completed a comprehensive neuropsychological battery at two to four study visits (Mean follow-up time = 2.6 years). Participants were divided into three PA groups: "No PA" (no PA at any visit), "consistent PA" (PA at ≥50% of visits), and "inconsistent PA" (PA

BACKGROUND:Cognitive deficits are common among individuals on haemodialysis (HD). The degree of dysfunction may shift over the course of the interdialytic interval. OBJECTIVES:To use ecological momentary assessment (EMA) to examine the relationship between the length of the interdialytic interval and reports of cognitive dysfunction. DESIGN:A quantitative study whereby each patient's cognitive functioning was measured during both short and long interdialytic intervals. PARTICIPANTS:Adults maintained on HD (Female n = 15, Male n = 11; MAge  = 42.7 ± 15.8 years) were drawn from a standalone HD unit within a large university medical centre. MEASUREMENTS:Tests of baseline neurocognitive functioning were undertaken (Mini-Mental Status Examination, Digit Span, California Verbal Learning Test, Benton Visual Retention Test, Trail-Making Test) and smartphone-based electronic diary reports of cognitive impairment were made around six times each day for one week. RESULTS:Cognitive function and aptitude in this sample, although low, did not reflect clinically-significant impairment, with a mean Mini-Mental Status Exam score of 25.7 ± 3.0. Diary reports of cognitive impairment were also minimal, with an overall mean rating of .22 out of 5. Contrary to expectations, cognitive impairment was significantly greater on the one-day interdialytic days than on Day 2 of the two-day interdialytic interval (β = .094, p = .017). CONCLUSIONS:Although cognitive impairment appears to be mild in stable, young patients with end stage renal disease, volumetric disruptions caused by HD may exacerbate such dysfunction.

OBJECTIVES:Amphetamine improves vigilance as assessed by continuous performance tests (CPT) in children and adults with attention deficit hyperactivity disorder (ADHD). Less is known, however, regarding amphetamine effects on vigilance in healthy adults. Thus, it remains unclear whether amphetamine produces general enhancement of vigilance or if these effects are constrained to the remediation of deficits in patients with ADHD. METHODS:We tested 69 healthy adults (35 female) on a standardized CPT (Conner's CPT-2) after receiving 10- or 20-mg d-amphetamine or placebo. To evaluate potential effects on learning, impulsivity, and perseveration, participants were additionally tested on the Iowa Gambling Task (IGT) and Wisconsin Card Sorting Task (WCST). RESULTS:Participants receiving placebo exhibited the classic vigilance decrement, demonstrated by a significant reduction in attention (D') across the task. This vigilance decrement was not observed, however, after either dose of amphetamine. Consistent with enhanced vigilance, the 20-mg dose also reduced reaction time variability across the task and the ADHD confidence index. The effects of amphetamine appeared to be selective to vigilance since no effects were observed on the IGT, WCST, or response inhibition/perseveration measures from the CPT. CONCLUSIONS:The present data support the premise that amphetamine improves vigilance irrespective of disease state. Given that amphetamine is a norepinephrine/dopamine transporter inhibitor and releaser, these effects are informative regarding the neurobiological substrates of attentional control. (JINS, 2018, 24, 283-293).

ImportanceThe ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies.ObjectiveTo determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of primary progressive aphasia (PPA).Design, setting, and participantsThis prospective clinical-pathologic case series was conducted at a tertiary research clinic specialized in cognitive disorders. Patients were evaluated as part of a prospective, longitudinal research study between January 2002 and December 2015. Inclusion criteria included clinical diagnosis of PPA; availability of complete speech, language, and cognitive testing; magnetic resonance imaging performed within 6 months of the cognitive evaluation; and PET carbon 11-labeled Pittsburgh Compound-B or florbetapir F 18 brain scan results. Of 109 patients referred for evaluation of language symptoms who underwent amyloid brain imaging, 3 were excluded because of incomplete language evaluations, 5 for absence of significant aphasia, and 12 for presenting with significant initial symptoms outside of the language domain, leaving a cohort of 89 patients with PPA.Main outcomes and measuresClinical, cognitive, neuroimaging, and pathology results.ResultsTwenty-eight cases were classified as imaging-supported semantic variant PPA (11 women [39.3%]; mean [SD] age, 64 [7] years), 31 nonfluent/agrammatic variant PPA (22 women [71.0%]; mean [SD] age, 68 [7] years), 26 logopenic variant PPA (17 women [65.4%]; mean [SD] age, 63 [8] years), and 4 mixed PPA cases. Twenty-four of 28 patients with semantic variant PPA (86%) and 28 of 31 patients with nonfluent/agrammatic variant PPA (90%) had negative amyloid PET scan results, while 25 of 26 patients with logopenic variant PPA (96%) and 3 of 4 mixed PPA cases (75%) had positive scan results. The amyloid positive semantic variant PPA and nonfluent/agrammatic variant PPA cases with available autopsy data (2 of 4 and 2 of 3, respectively) all had a primary frontotemporal lobar degeneration and secondary Alzheimer disease pathologic diagnoses, whereas autopsy of 2 patients with amyloid PET-positive logopenic variant PPA confirmed Alzheimer disease. One mixed PPA patient with a negative amyloid PET scan had Pick disease at autopsy.Conclusions and relevancePrimary progressive aphasia variant diagnosis according to the current classification scheme is associated with Alzheimer disease biomarker status, with the logopenic variant being associated with carbon 11-labeled Pittsburgh Compound-B positivity in more than 95% of cases. Furthermore, in the presence of a clinical syndrome highly predictive of frontotemporal lobar degeneration pathology, biomarker positivity for Alzheimer disease may be associated more with mixed pathology rather than primary Alzheimer disease.

Urolithiasis has become more prevalent in recent years, given the rapid rise of the global geriatric population. Although factors such as ethnicity, dietary and fluid intake, co-morbidity status and age have been associated with increased incidence of urolithiasis, the links between frailty status and risks of developing urolithiasis are not yet known. In this commentary, we will explore the scale and significance of this relationship based on emerging evidence. We will review the plausible factors on how a more severe frailty status may be significantly associated with greater risks of developing urolithiasis. We will also discuss the strategies that may help to lower the incidence of urolithiasis in older and frail individuals. We hope our article will bring greater awareness on this issue and motivate further research initiatives evaluating the relationship between frailty and urolithiasis, as well as holistic prevention strategies to lower the risks of developing urolithiasis within this vulnerable population.

A vision care-based community service subject is offered to general university students for fulfillment of a service-learning compulsory credit requirement. Here, a professional health subject is taught in a way that caters to generalist learners. Students gain basic skills they can apply to provide vision screenings for the needy population. All enrolled undergraduates had no background in eye health-related subjects. The teaching was not content-driven, requiring students' direct recall of facts. Rather, the teaching focused on Socratic teaching of logical theories and applications. The objective was to increase awareness of current eye care problems using case examples. Students learned to appreciate ways to promote active outreach services. Through activities and project work, students learned and practiced strong teamwork and direct application of knowledge in community-based eye care services. This learning experience demonstrates emergence of authentic practice from theory.

Multiple studies propose that English proficiency dictates English language learners' (ELLs) performances on mathematics assessments. The current study investigates the predictive power of English proficiency on mathematics scores, while controlling for gender, socioeconomic status (SES), and grade level among ELLs at a south Florida elementary school. Krashen's theory of comprehensible input as a precursor to second language acquisition provides the framework for this quantitative, correlation study. Mathematics scores from the Florida Comprehensive Assessment Test for Grade 3-5 ELLs (N = 177) were analyzed using multiple linear regression. Analysis reveals English proficiency as a statistically significant predictor of mathematics scores. Mathematics scores increase simultaneously with English proficiency but inversely with grade level. Grade level moderates the influence of English proficiency on mathematics scores. Gender and SES have no significant moderating influence.