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Background: Active surveillance (AS) for prostate cancer (PCa) is a monitoring pathway for men with low-grade, slow growing PCa and aims to delay or avoid active treatment by treating only in the case of disease progression. Experiences of this pathway vary but living with an untreated cancer can have a negative psychological impact on both the patient and their significant other (SO). Literature suggests partners are the primary source of support for men on AS, and therefore it is important to consider SO experiences alongside those of the patient. To the best of our knowledge this is the first UK-based qualitative review looking specifically at experiences of AS for both men with PCa and their SOs. Methods: MEDLINE (Ovid), EMBASE, PsychINFO, CINAHL and Cochrane Library were searched for literature reporting qualitative experiences of AS for PCa for either men on AS or SOs (or both). 2769 records were identified and screened, with 28 meeting the eligibility criteria. Qualitative data were synthesised and included men on AS (n = 428), and SOs (n = 51). Results: Experiences of the AS pathway vary but reports of uncertainty and anxiety were present in the accounts of both men on AS and SOs. SOs are intertwined throughout every part of the PCa journey, and couples presented as a unit that were on AS together. Both patients and SOs expressed a need for more support, and highly valued peer support. Despite this finding, men expressed a dislike towards 'support groups'. Conclusions: Increased recognition in clinical practice of SO involvement in AS is needed. Further research is required to explore the specific types of support that would be most acceptable to this population to address the unmet support needs uncovered in this review. [ABSTRACT FROM AUTHOR]

Background: Parents play a central role in the treatment of childhood stuttering. Addressing parental attitudes toward stuttering is helpful therapeutically. The extent to which differences in attitudes toward stuttering exist on the basis of sex, geographical region and parental status (e.g., parent of a stuttering child, parent of a nonstuttering child, nonparent) is unclear. Many studies investigating such factors have used the Public Opinion Survey of Human Attributes–Stuttering (POSHA–S) questionnaire. A large POSHA–S database has collected responses from over 20 000 people from 49 countries. Aims: The aim of this study was to use the POSHA‐S database to examine the extent to which the following variables influence attitudes toward stuttering: (a) parents' sex (mothers vs. fathers), (b) geographic region (Middle East vs. Europe and North America), (c) parents' children (stuttering vs. nonstuttering) and (d) parental status (parents versus nonparents). Methods & Procedures: Data used in this study were extracted from selected, relevant studies that administered the POSHA–S to respondents. The Overall Stuttering Scores were compared on the basis of sex and parent status (i.e., mothers and fathers; nonparent women and men) and were then compared within and across the two geographical areas. Group comparisons were performed using analysis of variance followed by independent t tests, and Cohen's d was calculated to determine effect sizes. Outcomes & Results: Statistically significant differences were observed upon the basis of geographical region. In general, male parents and nonparents tend to have more positive stuttering attitudes among the Middle Eastern samples while female parents and nonparents tend to show more positive attitudes in European and North American samples in the POSHA–S database. Effect sizes were small for all comparisons. Conclusions & Implications: The effect of geographic region and culture may predict sex‐based differences among mothers' and fathers' attitudes toward stuttering; however, the clinical significance is unclear. Additional research is needed to better understand how children who stutter are affected by their parents' attitudes toward stuttering. What this paper adds: What is already known on this subject: The research clearly indicates that attitudes toward stuttering vary according to geographical region. Less clear is whether mothers and fathers from geographically diverse backgrounds hold different attitudes toward stuttering and the extent to which parental status (being a parent, parent of a child who stutters or nonparent) affects attitudes toward stuttering. What this study adds: This study's findings confirm that geographical differences do influence attitudes toward stuttering. Male parents and nonparents tend to have equal or more positive attitudes toward stuttering in Middle Eastern samples, whereas non‐Middle Eastern female parents and nonparents tend to show hold more positive attitudes. What are the clinical implications of this work?: In addition to being culturally sensitive when working with parents of children who stutter, clinicians should also consider that mothers and fathers may have some differences in attitudes and behaviours toward their child's stuttering. These differences should be considered when designing treatment plans. It should also be noted that, despite statistical significance, the effect sizes in this study were low, suggesting that further research as well as close collaboration with parents of children who stutter is warranted. [ABSTRACT FROM AUTHOR]

Objectives: To investigate maternal antibody levels to varicella in infants <12 months of age in Ontario, Canada. Study design: In this study, we included specimens from infants <12 months of age, born at ≥37 weeks gestational age, who had sera collected at The Hospital for Sick Children (Toronto, Canada) between 2014–2016. We tested sera using a glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). We measured varicella susceptibility (antibody concentration <150mIU/mL) and mean varicella antibody concentration, and assessed the probability of susceptibility and concentration between one and 11 months of age using multivariable logistic regression and Poisson regression. Results: We found that 32% of 196 included specimens represented infants susceptible to varicella at one month of age, increasing to nearly 80% at three months of age. At six months of age, all infants were susceptible to varicella and the predicted mean varicella antibody concentration declined to 62 mIU/mL (95% confidence interval 40, 84), well below the threshold of protection. Conclusions: We found that varicella maternal antibody levels wane rapidly in infants, leaving most infants susceptible by four months of age. Our findings have implications for the timing of first dose of varicella-containing vaccine, infection control measures, and infant post-exposure prophylaxis recommendations. [ABSTRACT FROM AUTHOR]

Objectives: To outline the planning, development and optimisation of a psycho-educational behavioural intervention for patients on active surveillance for prostate cancer. The intervention aimed to support men manage active surveillance-related psychological distress. Methods: The person-based approach (PBA) was used as the overarching guiding methodological framework for intervention development. Evidence-based methods were incorporated to improve robustness. The process commenced with data gathering activities comprising the following four components: • A systematic review and meta-analysis of depression and anxiety in prostate cancer • A cross-sectional survey on depression and anxiety in active surveillance • A review of existing interventions in the field • A qualitative study with the target audience The purpose of this paper is to bring these components together and describe how they facilitated the establishment of key guiding principles and a logic model, which underpinned the first draft of the intervention. Results: The prototype intervention, named PROACTIVE, consists of six Internet-based sessions run concurrently with three group support sessions. The sessions cover the following topics: lifestyle (diet and exercise), relaxation and resilience techniques, talking to friends and family, thoughts and feelings, daily life (money and work) and information about prostate cancer and active surveillance. The resulting intervention has been trialled in a feasibility study, the results of which are published elsewhere. Conclusions: The planning and development process is key to successful delivery of an appropriate, accessible and acceptable intervention. The PBA strengthened the intervention by drawing on target-user experiences to maximise acceptability and user engagement. This meticulous description in a clinical setting using this rigorous but flexible method is a useful demonstration for others developing similar interventions. Trial registration and Ethical Approval: ISRCTN registered: ISRCTN38893965. NRES Committee South Central – Oxford A. REC reference: 11/SC/0355 [ABSTRACT FROM AUTHOR]

Objective: To explore primary care practitioners' (PCPs) and patients' priorities and concerns for healthcare interactions for osteoarthritis (OA) in primary care.Methods: We searched Embase, CINAHL, Medline, PsychInfo (1990 to present) for primary qualitative and mixed methods studies with findings concerning healthcare interactions for OA symptoms. Patient and PCP perceptions were analysed separately then inter-related using a 'line of argument' synthesis.Results: Twenty-six studies reporting qualitative data from 557 patients and 199 PCPs were synthesised. Our findings suggest that therapeutic interactions for OA can be based on discordant priorities and concerns; some patients perceive that PCPs hold negative attitudes about OA and feel their concerns about impact are not appreciated; some PCPs feel patients have misconceptions about prognosis, and hold pessimistic views about outcomes; and both tend to de-prioritise OA within consultations.Conclusion: Greater working in partnership could build mutual trust, facilitate tailored provision of information, and foster a shared understanding of OA upon which to build realistic goals for management.Practice Implications: Developing a better shared understanding of OA has the potential to improve the quality of healthcare interactions for both patients and PCPs. The significant impact of OA on everyday life means it should be given higher priority in primary care consultations. [ABSTRACT FROM AUTHOR]

Background Many studies assume that the serologic correlate of protection from measles disease is 120 mIU/mL. We systematically reviewed the literature to examine the evidence supporting this correlate of protection. Methods We searched peer-reviewed and gray literature for articles reporting a measles correlate of protection. We excluded studies focusing on special populations, infants aged <9 months, and those using animal models or nonstandard vaccines or administration routes. We extracted and synthesized data from full-text articles that met inclusion criteria. Results We screened 14 778 articles and included 5 studies in our review. The studies reported either preexposure antibody concentrations of individuals along with a description of symptoms postexposure, or the proportion of measles cases that had preexposure antibody concentrations above a threshold of immunity specified by the authors. Some studies also described secondary antibody responses upon exposure. The variation in laboratory methods between studies made comparisons difficult. Some of the studies that assumed 120 mIU/mL as a correlate of protection identified symptomatic individuals with preexposure titers exceeding this threshold. Conclusions Our findings underscore the scant data upon which the commonly used 120 mIU/mL measles threshold of protection is based, suggesting that further work is required to characterize the measles immunity threshold. [ABSTRACT FROM AUTHOR]

Individuals with an ostomy (a surgical diversion of part of the digestive tract through the abdomen) face a variety of uncertainties, due to the chronic and anatomy-altering nature of living with an ostomy, as well as the perceived stigma attached to having one. However, little is known about how these individuals negotiate uncertainty, and more specifically, how they manage the information they receive and disclose in the uncertainty management process. Thus, through 21 semi-structured interviews of individuals with an ostomy and the use of Uncertainty Management Theory as a theoretical framework, the current study found individuals with an ostomy attempted to negotiate uncertainty by managing information received and disclosed and by adapting to chronic uncertainty. This investigation recommends practical applications for medical professionals, supportive others, patients with an ostomy, as well as future surgical candidates to help manage uncertainty. [ABSTRACT FROM AUTHOR]

In settings where measles has been eliminated, vaccine-derived immunity may in theory wane more rapidly due to a lack of immune boosting by circulating measles virus. We aimed to assess whether measles vaccine effectiveness (VE) waned over time, and if so, whether differentially in measles-eliminated and measles-endemic settings. We performed a systematic literature review of studies that reported VE and time since vaccination with measles-containing vaccine (MCV). We extracted information on case definition (clinical symptoms and/or laboratory diagnosis), method of vaccination status ascertainment (medical record or vaccine registry), as well as any biases which may have arisen from cold chain issues and a lack of an age at first dose of MCV. We then used linear regression to evaluate VE as a function of age at first dose of MCV and time since MCV. After screening 14,782 citations, we identified three full-text articles from measles-eliminated settings and 33 articles from measles-endemic settings. In elimination settings, two-dose VE estimates increased as age at first dose of MCV increased and decreased as time since MCV increased; however, the small number of studies available limited interpretation. In measles-endemic settings, one-dose VE increased by 1.5% (95% CI 0.5, 2.5) for every month increase in age at first dose of MCV. We found no evidence of waning VE in endemic settings. The paucity of data from measles-eliminated settings indicates that additional studies and approaches (such as studies using proxies including laboratory correlates of protection) are needed to answer the question of whether VE in measles-eliminated settings wanes. Age at first dose of MCV was the most important factor in determining VE. More VE studies need to be conducted in elimination settings, and standards should be developed for information collected and reported in such studies. [ABSTRACT FROM AUTHOR]

Clinical empathy can enhance patient outcomes. This study examined patients' perceptions of empathy in primary care consultations delivered by telephone. A mixed methods study was nested in a larger feasibility study conducted May-October 2020. Adults reporting a UK primary care consultation in the previous 2 weeks completed an online survey. A sample of survey respondents participated in a semi-structured qualitative interview. Interviews were analysed thematically. Survey respondents (n = 359) rated practitioners as between 'good' and 'very good' at established patient-reported indicators of clinical empathy. Telephone consultations were rated slightly lower than face-to-face or other consultations. 30 survey respondents were interviewed. Three qualitative themes identified how telephone consultations can shape clinical empathy: setting for an empathic encounter; feeling connected; being acknowledged. Primary care patients typically perceive good levels of clinical empathy in telephone consultations; specific features of telephone consultations may facilitate and/or hinder clinical empathy. To ensure patients feel listened to, acknowledged and understood, practitioners may need to increase their empathic verbalisations in telephone consultations. By using verbal responses to demonstrate active listening and by clearly describing and/or implementing next steps in management, practitioners may be able to enhance clinical empathy in telephone consultations. • Clinical empathy can improve patient outcomes. • Patients reported good clinical empathy in primary care telephone consultations. • Patients rated telephone consultations slightly less empathic than other types. • We show how telephone consultations may facilitate and/or hinder clinical empathy. • Verbal signs of listening may enhance empathy in telephone consultations. [ABSTRACT FROM AUTHOR]

Clinical outcomes, including performance on cognitive assessment, in patients with angiographically negative subarachnoid haemorrhage (anSAH) are often interpreted as benign with a good prognostic trajectory. However, diffuse cognitive deficits have been reported within this patient cohort resulting from anSAH, albeit to a lesser extent when compared to other neurovascular events. We consider cognitive outcomes in relation to anSAH to systematically review reported deficits, with a view to quantify and categorise cognitive impairment in this cohort. Anxiety and depression were also included within this review, provided they were assessed alongside cognitive function. Performance deficits in attention and executive function are commonly reported, with set-shifting and interference tasks most commonly impaired in patients. Non-executive cognitive functions are negatively implicated also. Clinical implications and hypotheses relating to the source of these deficits are discussed. This review was formally registered with PROSPERO (CRD42017075294). [ABSTRACT FROM AUTHOR]

Secreted amyloid precursor protein alpha (sAPPα), processed from a parent mammalian brain protein, amyloid precursor protein, can modulate learning and memory. Recently it has been shown to modulate the transcriptome and proteome of human neurons, including proteins with neurological functions. Here, we analysed whether the acute administration of sAPPα facilitated changes in the proteome and secretome of mouse primary astrocytes in culture. Astrocytes contribute to the neuronal processes of neurogenesis, synaptogenesis and synaptic plasticity. Cortical mouse astrocytes in culture were exposed to 1 nM sAPPα, and changes in both the whole-cell proteome (2 h) and the secretome (6 h) were identified with Sequential Window Acquisition of All Theoretical Fragment Ion Spectra–Mass Spectrometry (SWATH-MS). Differentially regulated proteins were identified in both the cellular proteome and secretome that are involved with neurologically related functions of the normal physiology of the brain and central nervous system. Groups of proteins have a relationship to APP and have roles in the modulation of cell morphology, vesicle dynamics and the myelin sheath. Some are related to pathways containing proteins whose genes have been previously implicated in Alzheimer's disease (AD). The secretome is also enriched in proteins related to Insulin Growth Factor 2 (IGF2) signaling and the extracellular matrix (ECM). There is the promise that a more specific investigation of these proteins will help to understand the mechanisms of how sAPPα signaling affects memory formation. [ABSTRACT FROM AUTHOR]

Background OMEGA is an integrated aquatic system to produce biofuels, treat and recycle wastewater, capture CO2, and expand aquaculture production. This system includes floating photobioreactors (PBRs) that will cover hundreds of hectares in marine bays. To assess the interactions of marine mammals and birds with PBRs, 9 × 1.3 m flat panel and 9.5 × 0.2 m tubular PBRs were deployed in a harbor and monitored day and night from October 10, 2011 to Janurary 22, 2012 using infrared video. To observe interactions with pinnipeds, two trained sea lions (Zalophus californianus) and one trained harbor seal (Phoca vitulina richardii) were observed and directed to interact with PBRs in tanks. To determine the forces required to puncture PBR plastic and the effects of weathering, Instron measurements were made with a sea otter (Enhydra lutris) tooth and bird beaks. Results A total of 1,445 interactions of marine mammals and birds with PBRs were observed in the 2,424 hours of video recorded. The 95 marine mammal interactions, 94 by sea otters and one by a sea lion had average durations of three minutes (max 44 min) and represented about 1% of total recording time. The 1,350 bird interactions, primarily coots (Fulica americana) and gulls (Larus occidentalis and L. californicus) had average durations of seven minutes (max. 170) and represented 5% of recording time. Interactive behaviors were characterized as passive (feeding, walking, resting, grooming, and social activity) or proactive (biting, pecking, investigating, and unspecified manipulating). Mammal interactions were predominantly proactive, whereas birds were passive. All interactions occurred primarily during the day. Ninety-six percent of otter interactions occurred in Winter, whereas 73% of bird interactions in Fall, correlating to their abundance in the harbor. Trained pinnipeds followed most commands to bite, drag, and haul-out onto PBRs, made no overt undirected interactions with the PBRs, but showed avoidance behavior to PBR tethers. Instron measurements indicated that sea-otter teeth and gull beaks can penetrate weathered plastic more easily than new plastic. Published data suggest that otter bites may penetrate plastics, but pecking forces are not sufficient to do so. Conclusions Otter and bird interactions with experimental PBRs were benign. Large-scale OMEGA systems are predicted to have both positive and negative environmental consequences. [ABSTRACT FROM AUTHOR]

Background: OMEGA is an integrated aquatic system to produce biofuels, treat and recycle wastewater, capture CO2, and expand aquaculture production. This system includes floating photobioreactors (PBRs) that will cover hundreds of hectares in marine bays. To assess the interactions of marine mammals and birds with PBRs, 9 × 1.3 m flat panel and 9.5 × 0.2 m tubular PBRs were deployed in a harbor and monitored day and night from October 10, 2011 to Janurary 22, 2012 using infrared video. To observe interactions with pinnipeds, two trained sea lions (Zalophus californianus) and one trained harbor seal (Phoca vitulina richardii) were observed and directed to interact with PBRs in tanks. To determine the forces required to puncture PBR plastic and the effects of weathering, Instron measurements were made with a sea otter (Enhydra lutris) tooth and bird beaks. Results: A total of 1,445 interactions of marine mammals and birds with PBRs were observed in the 2,424 hours of video recorded. The 95 marine mammal interactions, 94 by sea otters and one by a sea lion had average durations of three minutes (max 44 min) and represented about 1% of total recording time. The 1,350 bird interactions, primarily coots (Fulica americana) and gulls (Larus occidentalis and L. californicus) had average durations of six minutes (max. 170) and represented 5% of recording time. Interactive behaviors were characterized as passive (feeding, walking, resting, grooming, and social activity) or proactive (biting, pecking, investigating, and unspecified manipulating). Mammal interactions were predominantly proactive, whereas birds were passive. All interactions occurred primarily during the day. Ninety-six percent of otter interactions occurred in winter, whereas 73% of bird interactions in fall, correlating to their abundance in the harbor. Trained pinnipeds followed most commands to bite, drag, and haul-out onto PBRs, made no overt undirected interactions with the PBRs, but showed avoidance behavior to PBR tethers. Instron measurements indicated that sea-otter teeth and gull beaks can penetrate weathered plastic more easily than new plastic. Conclusions: Otter and bird interactions with experimental PBRs were benign. Large-scale OMEGA systems are predicted to have both positive and negative environmental consequences. [ABSTRACT FROM AUTHOR]

Abstract: The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are inherited neurodegenerative lysosomal storage diseases caused by mutations in several different genes. Mutations in CLN5 cause a variant late-infantile human disease and some cases of juvenile and adult clinical disease. NCLs also occur in animals, and a flock of New Zealand Borderdale sheep with a CLN5 splice-site mutation has been developed for model studies. Dissociated mixed neural cells from CLN5-deficient foetal sheep brains contained no obvious storage bodies at plating but these accumulated rapidly in culture, mainly in microglial cells and also in neurons and astrocytes. Accumulation was very obvious after a week, as monitored by fluorescent microscopy and immunostaining for subunit c of mitochondrial ATP synthase. Photography at intervals revealed the dynamic nature of the cultures and a flow of storage bodies between cells, specifically the phagocytosis of storage-body containing cells by microglia and incorporation of the storage bodies into the host cells. No storage was observed in cultured control cells. Transduction of cell cultures with a lentiviral vector expressing a C-terminal Myc tagged CLN5 resulted in secretion of post-translationally glycosylated and processed CLN5. Transduction of CLN5-deficient cultures with this construct rapidly reversed storage body accumulation, to less than half in only six days. These results show that storage body accumulation is reversible with enzyme correction and support the use of these cultures for testing of therapeutics prior to whole animal studies. [Copyright &y& Elsevier]

Purpose: The purpose of this tutorial is to introduce speech-language pathologists (SLPs) to the broad issues surrounding the problem of school bullying in childhood and adolescence. Specifically, types of bullying and their causes are considered, as are the roles students take when bullying occurs and the effects of bullying on students with communication disorders. Strategies and suggestions to help SLPs more effectively prevent and manage bullying of students with communication disorders are discussed. Method: A review of the scholarly literature in education, psychology, child and adolescent development, and speech-language pathology was conducted. Recommendations for how SLPs can prevent and intervene in bullying incidences were extrapolated from the reviewed literature. Results: Students with communication disorders are at particularly high risk for being bullied by peers. Some students with communication disorders are "provocative victims" in that they demonstrate impairments in social skills that draw the attention of bullies. Both provocative victims and typical students may react aggressively when bullied and bully others in retaliation. Conclusion: SLPs can and should help to create an inclusive environment for all students while addressing bullying of students with communication disorders via therapeutic activities. [ABSTRACT FROM AUTHOR]

Dehydrins protect plant proteins and membranes from damage during drought and cold. Vitis riparia K2 is a 48-residue protein that can protect lactate dehydrogenase from freeze-thaw damage by preventing the aggregation and denaturation of the enzyme. To further elucidate its mechanism, we used a series of V. riparia K2 concatemers (K4, K6, K8, and K10) and natural dehydrins (V". riparia YSK2, 60 kilodalton peach dehydrin [PCA60], barley dehydrin5 [Dhn5], Thellungiella salsuginea dehydrin2 [TsDHN-2], and Opuntia streptacantha dehydrinl [OpsDHN-1]) to test the effect of the number of K-segments and dehydrin size on their ability to protect lactate dehydrogenase from freeze-thaw damage. The results show that the larger the hydrodynamic radius of the dehydrin, the more effective the cryoprotection. A similar trend is observed with polyethylene glycol, which would suggest that the protection is simply a nonspecific volume exclusion effect that can be manifested by any protein. However, structured proteins of a similar range of sizes did not show the same pattern and level of cryoprotection. Our results suggest that with respect to enzyme protection, dehydrins function primarily as molecular shields and that their intrinsic disorder is required for them to be an effective cryoprotectant. Lastly, we show that the cryoprotection by a dehydrin is not due to any antifreeze protein-like activity, as has been reported previously. [ABSTRACT FROM AUTHOR]

Given their coastal site fidelity and opportunistic foraging behavior, harbor seals ( Phoca vitulina) may serve as sentinels for coastal ecosystem health. Seals using urbanized coastal habitat can acquire enteric bacteria, including Vibrio that may affect their health. To understand Vibrio dynamics in seals, demographic and environmental factors were tested for predicting potentially virulent Vibrio in free-ranging and stranded Pacific harbor seals ( Phoca vitulina richardii) off California. Vibrio prevalence did not vary with season and was greater in free-ranging seals (29 %, n = 319) compared with stranded seals (17 %, n = 189). Of the factors tested, location, turbidity, and/or salinity best predicted Vibrio prevalence in free-ranging seals. The relationship of environmental factors with Vibrio prevalence differed by location and may be related to oceanographic or terrestrial contributions to water quality. Vibrio parahaemolyticus, Vibrio alginolyticus, and Vibrio cholerae were observed in seals, with V. cholerae found almost exclusively in stranded pups and yearlings. Additionally, virulence genes (trh and tdh) were detected in V. parahaemolyticus isolates. Vibrio cholerae isolates lacked targeted virulence genes, but were hemolytic. Three out of four stranded pups with V. parahaemolyticus (trh+ and/or tdh+) died in rehabilitation, but the role of Vibrio in causing mortality is unclear, and Vibrio expression of virulence genes should be investigated. Considering that humans share the environment and food resources with seals, potentially virulent Vibrio observed in seals also may be of concern to human health. [ABSTRACT FROM AUTHOR]

Background STARRT recently demonstrated that many patients experience suboptimal dialysis starts (defined as initiation as an inpatient and/or with a central venous catheter), even when followed by a nephrologist for >12 months (NDT 2011). However, STARRT did not identify the factors associated with suboptimal initiation of dialysis. The objectives of this study were to extend the results of STARRT by ascertaining the factors leading to suboptimal initiation of dialysis in patients who were referred at least 12 months prior to commencement of dialysis. Methods At each of the three Toronto centers, charts of consecutive incident RRT patients were identified from 1 January 2009 to 31 December 2010, with predetermined data extracted. Results A total of 436 incident RRT patients were studied; 52.4% were followed by a nephrologist for >12 months prior to the initiation of dialysis. Suboptimal starts occurred in 56.4% of these patients. No attempt at arteriovenous fistula (AVF) or arteriovenous graft (AVG) prior to initiation was made in 65% of these starts. Factors contributing to suboptimal starts despite early referral included patient-related delays (31.25%), acute-on-chronic kidney disease (31.25%), surgical delays (16.41%), late decision-making (8.59%) and others (12.50%). The percentage of optimal starts with early referral among 14 nephrologists ranged from 33 to 72%. Conclusions Most patients started dialysis in a suboptimal manner, despite an extended period of pre-dialysis care. Nephrologists should take responsibility for suboptimal initiation of dialysis despite early referral and test methods that attempt to prevent this. [ABSTRACT FROM AUTHOR]

Abstract: Hydrogen peroxide is widely viewed as the main second messenger in redox signaling, and it has been proposed that deactivation of the antioxidant peroxiredoxin (Prdx) enzymes allows free peroxide to accumulate and directly oxidize target proteins (the floodgate model). We assessed the role of cytosolic Prdxs 1 and 2 in peroxide-induced activation of the apoptosis signaling kinase 1 (ASK1)/p38 signaling pathway, in which oxidation of ASK1 is required for phosphorylation of p38. In response to peroxide, Prdx1 catalyzed oxidation of ASK1 to a disulfide-linked multimer, and this occurred via transient formation of a Prdx1—ASK1 mixed disulfide intermediate. Oxidation of ASK1 and phosphorylation of p38 were inhibited by knockdown of Prdx1, but also by overexpression of Prdx2. This suggests that these two cytosolic Prdxs have distinct roles in the cellular peroxide response and compete for available peroxide substrate. These data imply that Prdx1 can function as a peroxide receptor in response to extracellular H2O2, receiving the peroxide signal and transducing it into a disulfide bond that is subsequently transmitted to the substrate, ASK1, resulting in p38 phosphorylation. Interestingly, in response to peroxide, Prdx1 and Prdx3 transiently formed reducible higher molecular weight complexes, suggesting that multiple proteins are targets for Prdx-mediated oxidation via a disulfide-exchange mechanism. This model of active peroxide signal distribution via disulfide exchange is consistent with Prdx function in yeast and explains how peroxides may trigger specific disulfide bond formation in mammalian cells. [Copyright &y& Elsevier]

Abstract: Strength training that overloads lengthening muscle fibers may result in greater strength gains with less effort and perceived exertion than conventional training modalities. This study evaluates a device capable of this overloading (a motor-driven and computer-controlled leg press) to develop recommendations for future training interventions. Unimpaired younger and older men and women (7/group, total n =28) performed three maximal-effort trials for both directions of footplate motion (IN and OUT) at three speed profiles (knee rotation speeds of 15, 25, and 35°/s) on a motor-driven and computer-controlled leg press. Normalized forces were tested for effects of age group, sex, direction of footplate motion, and knee rotation speed. Peak forces were 57% greater for younger and 20% greater for IN. Trends of greater IN relative to OUT forces (IN overloading) were present in women, but this was due to an inverse correlation between strength and IN overloading that was independent of age group and sex. Leg press strength training on a device that is capable of overloading lengthening muscle fibers is a promising new training method that appears to have the greatest potential benefits for the weakest participants. Training target profiles on the device tested and others similar to it should be set based on participant-specific maximums across the ROM in both IN and OUT directions at a speed in the middle of the range to be trained. [Copyright &y& Elsevier]

Abstract: This study describes the relationship between acoustic characteristics, self-ratings, and listener-ratings of public speaking. The specific purpose of this study was to examine the effects of anxiety and practice on speech and voice during public speaking. Further examination of the data was completed to examine the illusion of transparency, which hypothesizes that public speakers think their anxiety is more noticeable to listeners than it really is. Self-rating and acoustic speech data were reported on two separate speeches produced by 16 college-aged individuals completing coursework in interpersonal communication. Results indicated that there were significant relationships between acoustic characteristics of speech and both self- and listener-ratings of anxiety in public speaking. However, self-ratings of anxiety were higher than listener ratings, indicating possible confirmation of the illusion of transparency. Finally, data indicate that practice patterns have a significant effect on the fluency characteristics of public speaking performance, as speakers who started practicing earlier were less disfluent than those who started later. Data are also discussed relative to rehabilitation for individuals with communication disorders that can be associated with public speaking anxiety. [Copyright &y& Elsevier]

Abstract: Semantic differential instruments are often used to assess fluent speakers’ attitudes toward people who stutter (PWS). Such instruments are prone to response bias and often lack the power to explain respondents’ general impressions of PWS. To address these concerns 149 fluent university students completed an open-ended questionnaire in which they described PWS and provided an explanation for their descriptions. A mixed model design with a qualitative emphasis allowed for thematic as well as quantitative data analysis. The results suggest that individuals may have simultaneously positive and negative attitudes toward PWS regardless of gender or familiarity with PWS. Multiple explanations were provided and took into account personal and societal reactions to stuttering. Fluent speakers appear to perceive PWS as being likeable individuals who are poor communicators, a combination of high-warmth and low-competence that elicits pity and passive harm from listeners according to social psychologists (). The implications of these findings and future research directions are discussed. Educational objectives: After reading this article, the reader will be able to: (1) describe issues of concern related to the measurement of attitudes toward PWS; (2) describe how mixed (qualitative and quantitative) designs can contribute to a deeper understanding of fluent speakers’ attitudes toward PWS; and (3) discuss how the ways in which fluent speakers’ thoughts about stuttering and PWS can influence their emotions and behaviors when in the presence of someone who stutters. [Copyright &y& Elsevier]

This chapter addresses the issue of higher education institution policies and procedures in regard to background checks for students, staff, and faculty in light of homeland security concerns. [ABSTRACT FROM AUTHOR]

The article presents a study to evaluate the quality and effectiveness of a professional training program. The Alzheimer's Association developed a survey to evaluate the Foundations training which will be used for program management purpose and identify the best practices for the program. The result shows that the participant's satisfaction and outcomes varies from the trainer and training sessions and the foundation of the training depends on the quality of the session and trainer.

Abstract: An open-ended, written survey was administered to 146 university students who did not stutter to obtain their impressions of the effects of stuttering on the lives of people who stutter (PWS). Participants first wrote about the general effects of stuttering and then considered how their lives would be different if they stuttered. Both types of responses, while not qualitatively different, indicated that participants were more likely to focus on negative listener reactions and barriers to social, academic, and occupational success when they imagined themselves as PWS. Fewer participants indicated that PWS may positively cope with their stuttering through acceptance of stuttering, motivation and determination, and support systems. Quantitative differences based on gender and familiarity with PWS were not observed. The findings suggest that while university students are generally sensitive to the issues which can affect PWS, they may also tend to exaggerate the limitations placed on PWS by their stuttering. Learner outcomes: The reader will be able to (1) understand the various ways in which fluent speakers perceive the life effects of stuttering; (2) discuss how fluent speakers, while apparently sensitive to the negative effects of stuttering, can also overemphasize the degree to which PWS are unable to participate effectively and autonomously in society; and (3) recognize the need for additional research in this area and for continued education of the general public and others by advocacy groups. [Copyright &y& Elsevier]

Background: The clinical literature cautions against use of meditation by people with psychosis. There is, however, evidence for acceptance-based therapy reducing relapse, and some evidence for clinical benefits of mindfulness groups for people with distressing psychosis, though no data on whether participants became more mindful. Aims: To assess feasibility of randomized evaluation of group mindfulness therapy for psychosis, to replicate clinical gains observed in one small uncontrolled study, and to assess for changes in mindfulness. Method: Twenty-two participants with current distressing psychotic experiences were allocated at random between group-based mindfulness training and a waiting list for this therapy. Mindfulness training comprised twice-weekly sessions for 5 weeks, plus home practice (meditation CDs were supplied), followed by 5 weeks of home practice. Results: There were no significant differences between intervention and waiting-list participants. Secondary analyses combining both groups and comparing scores before and after mindfulness training revealed significant improvement in clinical functioning (p = .013) and mindfulness of distressing thoughts and images (p = .037). Conclusions: Findings on feasibility are encouraging and secondary analyses replicated earlier clinical benefits and showed improved mindfulness of thoughts and images, but not voices. [ABSTRACT FROM AUTHOR]

High-profile criminal acts continue to plague United States (US) college campuses despite recent efforts to implement more aggressive risk mitigation practices, such as criminal background checks. Despite these efforts, incidents such as the most recent shootings at Virginia Polytechnic Institute and State University continue to demonstrate that, although these efforts are welcome, they are not enough to address the ever-increasing risks facing universities. This article addresses some of the gaps in existing risk mitigation efforts on US college campuses and examines a relatively new incident reporting technology that is fast gaining acceptance as an additional and ongoing risk mitigation tool for these environments. [ABSTRACT FROM AUTHOR]

This study examined whether individuals with a laryngectomy are at risk for stereotyping and victim blaming. Undergraduate students (3 men and 41 women) volunteered to listen to a recording of a man who used tracheoesophageal speech or a man who was a typical adult speaker. A written vignette was provided prior to the listening activity to assess whether knowing that the speaker did or did not have a history of smoking affected the listeners' judgments of the speaker. Semantic differential data and qualitative responses indicated that participants did not report victim blaming; however, they did report that users of tracheoesophageal speech were less highly employable than typical adult speakers. Participants also indicated they relied on the vocal characteristics of speakers and used empathy- or experienced-based reactions to make judgments about users of such speech. [ABSTRACT FROM AUTHOR]

Abstract: The primary purpose of this study was to examine whether a group of university students would report role entrapment of people who stutter (PWS) in the form of occupational stereotyping. The study also examined whether severity of stuttering (mild or severe) and level of therapy involvement (choosing or not choosing to attend therapy) affected the perceptions of role entrapment. To examine these issues, 260 students completed the Vocational Advice Scale (VAS) [Gabel, R. M., Blood, G. W., Tellis, G., & Althouse, M. T. (2004). Measuring role entrapment of people who stutter. Journal of Fluency Disorders, 29, 27–49]. Results suggested that stuttering severity and the level of therapy involvement did not appear alter the judges’ reports for all of the careers except for the career of speech therapist. For the career of speech therapist, therapy involvement improved the participants’ reports and stuttering severity had no effect. Additionally, findings suggested that university students reported that 16 of the careers listed on the VAS were appropriate choices for people who stutter and were less certain about advising for 27 of the careers. Thus, the findings from this study do not support the notion that stuttering leads to role entrapment in the form vocational stereotyping and variations in therapy involvement or stuttering severity do not change perceptions of role entrapment. Learner outcomes: The reader will be able to (1) identify common stereotypes of PWS, (2) describe the possible effects of stereotyping and role entrapment, and (3) describe the effects of severity and therapy involvement of role entrapment of PWS. [Copyright &y& Elsevier]

Abstract: Microglia and astrocytes play vital roles in normal human brain function and in neurological disorders. To study their physiological and pathological roles it is desirable to establish in vitro systems that are derived from the adult human brain. Although several groups have successfully cultured cells from the human brain, the composition of these cultures remains controversial. Using morphological criteria, immunocytochemical analysis and a BrdU incorporation assay we demonstrate the presence of poorly proliferative microglia and astrocytes in cultures derived from epilepsy biopsy tissue. In addition, we characterized a third cell type as fibronectin and prolyl 4-hydroxylase immunopositive fibroblast-like cells, which are highly proliferative and become the predominant cell type after successive sub-culturing. Therefore, although cultures from adult human brain tissue provide an excellent resource for studying human glial cells, careful consideration must be given to their cellular composition when performing studies using these methods. [Copyright &y& Elsevier]

Brain-derived neurotrophic factor (BDNF) plays a major role in regulating the survival and fate of progenitor cells in the adult brain. In order to extend previous observations in the normal adult brain and advance our knowledge regarding the effect of BDNF on neurogenesis in the injured brain, this study directly compared the effect of BDNF on basal and injury-induced neurogenesis in relation to progenitor cell distribution and levels of neuronal differentiation and survival. BDNF was overexpressed in the subventricular zone (SVZ) via recombinant adeno-associated virus (AAV1/2) delivery, and newly generated cells were identified using bromodeoxyuridine (BrdU) labelling. Selective striatal cell loss was induced in a subgroup of rats by unilateral striatal injection of quinolinic acid (QA) 21 days after AAV1/2 injection. In the normal brain, BDNF overexpression significantly increased BrdU-positive cell numbers in the rostral migratory stream, indicating enhanced progenitor cell migration. Following QA lesioning, we observed a reduction in BrdU immunoreactivity in the SVZ. Overexpression of BDNF restored BrdU-positive cell numbers in the QA-lesioned SVZ to that observed in the normal brain. Most significantly, BDNF enhanced the recruitment of progenitor cells to the QA-lesioned striatum and promoted neuronal differentiation in both the normal and QA-lesioned striatum. Our findings indicate that BDNF augments the recruitment, neuronal differentiation and survival of progenitor cells in both neurogenic and non-neurogenic regions of the normal or QA-lesioned brain. Enhanced expression of BDNF may therefore be a viable strategy for augmenting neurogenesis from endogenous progenitor cells. [ABSTRACT FROM AUTHOR]

The consequences of falls among the elderly are often devastating and include injury, increased morbidity and mortality, loss of independence, fear, decreased activity level, additional treatment expenses and decreased quality of life. An Evidence-Based Program to Prevent Patient Falls was implemented which instituted Fall Clinics, staffed by interdisciplinary teams. The goals of these Fall Clinics were to assess severity of fall risk, establish the etiology of falls and develop a fall specific plan of care. The purpose of this article is to discuss the functional profile of veterans referred to these fall clinics, their fall rates and fall team prevention treatment plan. Over a 2-year period, data from 571 consented clinic patients were obtained. The most notable finding obtained was a 3-fold reduction in falls following the initial Fall Clinic visit when compared to pre-clinic values. These data further supports existing literature regarding the need for multi-dimensional, evidence-based fall prevention interventions in order to address this widespread patient safety issue. [ABSTRACT FROM AUTHOR]

Gene therapy in the brain has focused mainly on neurons (gray matter), with little comparable research on white matter. In this study, injections into mice cerebral white matter of mice were done to assess the distribution of gene transfer with recombinant feline immunodeficiency virus vectors expressing either β-galactosidase or β-glucuronidase. Our results show that vectors were preferentially distributed along the white matter of the external capsule, which was the site of vector injection as confirmed by horseradish peroxidase labeling. Moreover, we found gene transfer almost exclusively to NeuN+ cells lining the external capsule, which then robustly secreted recombinant β-glucuronidase throughout the white matter of the entire external capsule on the injected side. These results may have application to lysosomal storage diseases with widespread central nervous system deficits, and other disorders such as multiple sclerosis and human immunodeficiency virus dementia. [Copyright &y& Elsevier]

Neural progenitor cells may provide for cell replacement or gene delivery vehicles in neurodegen-erative disease therapies. The expression of therapeutic proteins by neural progenitors would be enhanced by viral-mediated gene transfer, but the effects of several common recombinant viruses on primary progenitor cell populations have not been tested. To address this issue, we cultured cells from embryonic day 16–18 mouse brain in serum-free medium containing epidermal growth factor or basic fibroblast growth factor, and investigated how transduction with recombinant viral vectors affected maintenance and differentiation properties of progenitor cells. Neurosphere cultures were incubated with feline immunodeficiency virus (FIV), adeno-associated virus (AAV) or ade-noviral (Ad) constructs expressing either β-galactosidase or enhanced green fluorescent protein at low multiplicity of infection. Nestin-positive neurospheres were regenerated after incubation of single progenitor cells with FIV, indicating that FIV-mediated gene transfer did not inhibit progenitor cell self-renewal. In contrast, adenovirus induced differentiation into glial fibrillary acidic protein (GFAP)-positive astrocytes. The AAV serotypes tested did not effectively transduce progenitor cells. FIV-transduced progenitors retained the potential for differentiation into neurons and glia in vitro, and when transplanted into the striatum of normal adult C57BL/6 mice differentiated into glia, or remained undifferentiated. In the presence of tumor cells, FIV-transduced progenitors migrated significantly from the injection site. Our results suggest that FIV-based vectors can transduce progenitor cell populations in vitro, with maintenance of their ability to differentiate into multiple cell types or to respond to injury within the central nervous system. These results hold promise for the use of genetically manipulated stem cells for CNS therapies. [Copyright &y& Elsevier]

Dopaminergic neurons are the predominant brain cells affected in Parkinson's disease. With the limited availability of live human brain dopaminergic neurons to study pathological mechanisms of Parkinson's disease, dopaminergic neurons have been generated from human-skin-cell-derived induced pluripotent stem cells. Originally, induced pluripotent stem-cell-derived dopaminergic neurons were generated using small molecules. These neurons took more than two months to mature. However, the transcription-factor-mediated differentiation of induced pluripotent stem cells has revealed quicker and cheaper methods to generate dopaminergic neurons. In this study, we compared and contrasted three protocols to generate induced pluripotent stem-cell-derived dopaminergic neurons using transcription-factor-mediated directed differentiation. We deviated from the established protocols using lentivirus transduction to stably integrate different transcription factors into the AAVS1 safe harbour locus of induced pluripotent stem cells. We used different media compositions to generate more than 90% of neurons in the culture, out of which more than 85% of the neurons were dopaminergic neurons within three weeks. Therefore, from our comparative study, we reveal that a combination of transcription factors along with small molecule treatment may be required to generate a pure population of human dopaminergic neurons. [ABSTRACT FROM AUTHOR]

Background: We conducted a systematic review to assess whether measles humoral immunity wanes in previously infected or vaccinated populations in measles elimination settings.Methods: After screening 16 822 citations, we identified 9 articles from populations exposed to wild-type measles and 16 articles from vaccinated populations that met our inclusion criteria.Results: Using linear regression, we found that geometric mean titers (GMTs) decreased significantly in individuals who received 2 doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% confidence interval [CI], -212.4 to -31.1) per year since vaccination over 1 to 5 years, 53.7 mIU/mL (95% CI, -95.3 to -12.2) 5 to 10 years, 33.2 mIU/mL (95% CI, -62.6 to -3.9), 10 to 15 years, and 24.1 mIU/mL (95% CI, -51.5 to 3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after 1 dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after 1 or 2 doses of MCV or after infection.Conclusions: Measles antibody waning in vaccinated populations should be considered in planning for measles elimination. [ABSTRACT FROM AUTHOR]

The NCLs (neuronal ceroid lipofuscinosis) are forms of neurodegenerative disease that affect people of all ages and ethnicities but are most prevalent in children. Commonly known as Batten disease, this debilitating neurological disorder is comprised of 13 different subtypes that are categorized based on the particular gene that is mutated (CLN1-8 , CLN10-14). The pathological mechanisms underlying the NCLs are not well understood due to our poor understanding of the functions of NCL proteins. Only one specific treatment (enzyme replacement therapy) is approved, which is for the treating the brain in CLN2 disease. Hence there remains a desperate need for further research into disease-modifying treatments. In this review, we present and evaluate the genes, proteins and studies performed in the social amoeba, nematode, fruit fly, zebrafish, mouse and large animals pertinent to NCL. In particular, we highlight the use of multicellular model organisms to study NCL protein function, pathology and pathomechanisms. Their use in testing novel therapeutic approaches is also presented. With this information, we highlight how future research in these systems may be able to provide new insight into NCL protein functions in human cells and aid in the development of new therapies. • Model organisms highlight mechanisms, protein functions and relevant pathways • A range of model organisms with various attributes enable in vivo experimentation • Therapeutic testing for NCLs relies on a range of suitable disease models [ABSTRACT FROM AUTHOR]

Background: Many studies assume that the serologic correlate of protection from measles disease is 120 mIU/mL. We systematically reviewed the literature to examine the evidence supporting this correlate of protection.Methods: We searched peer-reviewed and gray literature for articles reporting a measles correlate of protection. We excluded studies focusing on special populations, infants aged <9 months, and those using animal models or nonstandard vaccines or administration routes. We extracted and synthesized data from full-text articles that met inclusion criteria.Results: We screened 14 778 articles and included 5 studies in our review. The studies reported either preexposure antibody concentrations of individuals along with a description of symptoms postexposure, or the proportion of measles cases that had preexposure antibody concentrations above a threshold of immunity specified by the authors. Some studies also described secondary antibody responses upon exposure. The variation in laboratory methods between studies made comparisons difficult. Some of the studies that assumed 120 mIU/mL as a correlate of protection identified symptomatic individuals with preexposure titers exceeding this threshold.Conclusions: Our findings underscore the scant data upon which the commonly used 120 mIU/mL measles threshold of protection is based, suggesting that further work is required to characterize the measles immunity threshold. [ABSTRACT FROM AUTHOR]

Besides respiratory illness, SARS-CoV-2, the causative agent of COVID-19, leads to neurological symptoms. The molecular mechanisms leading to neuropathology after SARS-CoV-2 infection are sparsely explored. SARS-CoV-2 enters human cells via different receptors, including ACE-2, TMPRSS2, and TMEM106B. In this study, we used a human-induced pluripotent stem cell-derived neuronal model, which expresses ACE-2, TMPRSS2, TMEM106B, and other possible SARS-CoV-2 receptors, to evaluate its susceptibility to SARS-CoV-2 infection. The neurons were exposed to SARS-CoV-2, followed by RT-qPCR, immunocytochemistry, and proteomic analyses of the infected neurons. Our findings showed that SARS-CoV-2 infects neurons at a lower rate than other human cells; however, the virus could not replicate or produce infectious virions in this neuronal model. Despite the aborted SARS-CoV-2 replication, the infected neuronal nuclei showed irregular morphology compared to other human cells. Since cytokine storm is a significant effect of SARS-CoV-2 infection in COVID-19 patients, in addition to the direct neuronal infection, the neurons were treated with pre-conditioned media from SARS-CoV-2-infected lung cells, and the neuroproteomic changes were investigated. The limited SARS-CoV-2 infection in the neurons and the neurons treated with the pre-conditioned media showed changes in the neuroproteomic profile, particularly affecting mitochondrial proteins and apoptotic and metabolic pathways, which may lead to the development of neurological complications. The findings from our study uncover a possible mechanism behind SARS-CoV-2-mediated neuropathology that might contribute to the lingering effects of the virus on the human brain. [ABSTRACT FROM AUTHOR]

In recent years, expansion of home and community-based services (HCBS) for older adults and persons with disabilities has become a national priority in the U.S. In addition, lawmakers and health-care providers are pursuing opportunities to minimize disparities in healthcare service delivery. Marrying these priorities will require policymakers to identify existing Medicaid HCBS disparities toward development of new, more equitable policies. This study provides a systematic literature review using an adapted theoretical framework to describe disparities in Medicaid HCBS. Key findings are organized into four domains: availability, accessibility, accommodation, and acceptability. We found a lack of concerted research effort targeting Medicaid HCBS disparities in the context of all four domains, with an especially notable dearth of content related to acceptability. We also identified very few articles that focused on specific marginalized groups, suggesting a need for more research into whether Medicaid HCBS are available, accessible, accommodating, and acceptable for a variety of diverse populations. Our findings underscore the need for researchers and policymakers to conceptualize and evaluate existing Medicaid HCBS policy toward development of a more equitable Medicaid HCBS program design in the future. [ABSTRACT FROM AUTHOR]

Model reactions have been performed to explore the reactivity of a variety of ureido groups with cyclohexane carboxaldehyde. The reaction mechanism between ureido and aldehyde functionalities is more complicated than expected. A new heterocyclic product was identified, which is very stable and solvent resistant. The final product profile is reactant and solvent dependent. In the cases of urea, alkyl urea, and benzyl urea, the reaction pathway goes from hemiaminal to aminal, to enamine, and finally to the heterocyclic product with nearly 100% yield. For other investigated ureido groups, the reaction stopped at the enamine product, and products are a mixture of hemiaminal, aminal, and enamine. All reaction steps are reversible except for the last step. The structure of the unique cyclic product was determined combining NMR and LC-MS analysis, and the reaction pathway was verified by kinetics studies. [ABSTRACT FROM AUTHOR]

The presence of ongoing neurogenesis in the adult mammalian brain raises the exciting possibility that endogenous progenitor cells could be used therapeutically for repair of neuronal loss associated with brain disease or injury. While previous studies have demonstrated that the adult brain has the potential for self-repair, it is apparent that the level of neurogenesis observed is insufficient to compensate for the progressive cell loss that occurs during brain injury and disease. In order for endogenous progenitor cells to be useful therapeutically, methods need to be developed to augment the process of neurogenesis and direct progenitor cells to proliferate, migrate and generate new neurons in specific areas of neuronal cell loss. Using in vivo gene transfer, we investigated the effect of Brain-Derived Neurotrophic Factor (BDNF) on the migration, differentiation and survival of endogenous progenitor cells in both the normal adult rat brain and the quinolinic acid (QA) lesion rat model of Huntington's disease (HD). We have developed a recombinant AAV vector encoding the human BDNF transgene under the control of the CBA constitutive promoter. Adult rats received unilateral stereotaxic injections of either AAV-BDNF, the control vector AAV-luciferase or sterile PBS into the anterior subventricular zone (SVZ). Three weeks later, the rats received daily injections of the mitotic marker bromodeoxyuridine (BrdU; 150 mg/kg i.p.) for 21 days in order to identify newly generated cells. Half of the rats also received a unilateral striatal injection of QA (50 nmol) in order to model HD. In the normal adult rat brain, BDNF over-expression had no effect on the number of BrdU labelled cells in the SVZ or striatum but resulted in a significant increase in BrdU labelling in the rostral migratory stream (RMS) compared to untreated animals (p≤0.01). In untreated animals that received a striatal QA lesion we observed a significant reduction in the number of BrdU labelled cells in the SVZ and RMS compared to unlesioned animals (p≤0.05) 21 days after lesioning, suggesting a chronic alteration in the dynamics of progenitor cell proliferation in response to QA lesioning. While BDNF over-expression did not alter the reduction in BrdU labelling observed in the RMS of QA lesioned animals, BDNF significantly increased the level of BrdU labelling in the SVZ of QA lesioned animals to that observed in unlesioned animals (p≤0.01). BDNF also greatly induced the level of BrdU-immunoreactivity observed in the QA lesioned striatum compared to untreated animals (p≤0.001). Furthermore, 9 weeks following QA lesioning we observed that BDNF over-expression had greatly enhanced the level of striatal neurogenesis observed in QA lesioned animals compared to untreated animals. These results demonstrate that over-expression of BDNF in the SVZ substantially augments the survival, migration and neuronal differentiation of progenitor cells in both neurogenic and non-neurogenic regions of the normal or QA lesioned adult rat brain, supporting the potential therapeutic use of endogenous neural progenitor cells for the treatment of HD.Molecular Therapy (2006) 13, S174–S174; doi: 10.1016/j.ymthe.2006.08.519 [ABSTRACT FROM AUTHOR]

Viral vectors were originally developed to deliver genes into host cells for therapeutic potential. However, viral vector use in neuroscience research has increased because they enhance interpretation of the anatomy and physiology of brain circuits compared with conventional tract tracing or electrical stimulation techniques. Viral vectors enable neuronal or glial subpopulations to be labeled or stimulated, which can be spatially restricted to a single target nucleus or pathway. Here we review the use of viral vectors to examine the structure and function of motor and limbic basal ganglia (BG) networks in normal and pathological states. We outline the use of viral vectors, particularly lentivirus and adeno-associated virus, in circuit tracing, optogenetic stimulation, and designer drug stimulation experiments. Key studies that have used viral vectors to trace and image pathways and connectivity at gross or ultrastructural levels are reviewed. We explain how optogenetic stimulation and designer drugs used to modulate a distinct pathway and neuronal subpopulation have enhanced our mechanistic understanding of BG function in health and pathophysiology in disease. Finally, we outline how viral vector technology may be applied to neurological and psychiatric conditions to offer new treatments with enhanced outcomes for patients. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD) has gained attention as a therapeutic agent and is purported to have immunomodulatory, neuroprotective, and anti-seizure effects. Here, we determined the effects of chronic CBD administration in a mouse model of CLN1 disease (Cln1−/−) that simultaneously exhibits neuroinflammation, neurodegeneration, and spontaneous seizures. Proteomic analysis showed that putative CBD receptors are expressed at similar levels in the brains of Cln1−/− mice compared to normal animals. Cln1−/− mice received an oral dose (100 mg/kg/day) of CBD for six months and were evaluated for changes in pathological markers of disease and seizures. Chronic cannabidiol administration was well-tolerated, high levels of CBD were detected in the brain, and markers of astrocytosis and microgliosis were reduced. However, CBD had no apparent effect on seizure frequency or neuron survival. These data are consistent with CBD having immunomodulatory effects. It is possible that a higher dose of CBD could also reduce neurodegeneration and seizure frequency. [ABSTRACT FROM AUTHOR]

Introduction: Neutrophil accumulation is a well-established feature of Alzheimer's disease (AD) and has been linked to cognitive impairment by modulating disease-relevant neuroinflammatory and vascular pathways. Neutrophils express high levels of the oxidant-generating enzyme myeloperoxidase (MPO), however there has been controversy regarding the cellular source and localisation of MPO in the AD brain. Materials and methods: We used immunostaining and immunoassays to quantify the accumulation of neutrophils in human AD tissue microarrays and in the brains of APP/PS1 mice. We also used multiplexed immunolabelling to define the presence of NETs in AD. Results: There was an increase in neutrophils in AD brains as well as in the murine APP/PS1 model of AD. Indeed, MPO expression was almost exclusively confined to S100A8-positive neutrophils in both human AD and murine APP/PS1 brains. The vascular localisation of neutrophils in both human AD and mouse models of AD was striking and driven by enhanced neutrophil adhesion to small vessels. We also observed rare infiltrating neutrophils and deposits of MPO around plaques. Citrullinated histone H3, a marker of neutrophil extracellular traps (NETs), was also detected in human AD cases at these sites, indicating the presence of extracellular MPO in the vasculature. Finally, there was a reduction in the endothelial glycocalyx in AD that may be responsible for non-productive neutrophil adhesion to the vasculature. Conclusion: Our report indicates that vascular changes may drive neutrophil adhesion and NETosis, and that neutrophil-derived MPO may lead to vascular oxidative stress and be a relevant therapeutic target in AD. [ABSTRACT FROM AUTHOR]

A disordered voice may lead to social stigma as well as reduced occupational opportunities. Much of the research on this topic has investigated the effects of voice disorders from a Western perspective. The societal attitudes of international populations toward people with voice disorders (PWVD) are less well known. The purpose of this study was to investigate the attitudes of adults living in Kuwait toward PWVD. Participants completed a questionnaire that addressed social, educational, and occupational aspects of life for PWVD. The results indicated that while Kuwaiti adults hold generally positive attitudes toward PWVD, they may also perceive PWVD as more likely to be emotionally disturbed, have difficulty making friends or getting married, and experience trouble in finding a good job. [ABSTRACT FROM AUTHOR]

Background: Maximum step length is a brief clinical test involving stepping out and back as far as possible with the arms folded across the chest. This test has been shown to predict fall risk, but the biomechanics of this test are not fully understood. Knee and hip kinetics (moments and powers) are greater for longer steps and for younger subjects, but younger subjects also step farther. Methods: To separate the effects of step length, age, and fall history on joint kinetics; healthy younger (age=27(5), N=14), older non-fallers (age=72(5), N=14), and older fallers (age=75(6), N=11) all stepped to the same relative target distances of 20–80% of their height. Knee and hip kinetics and knee co-contraction were calculated. Findings: Hip and knee kinetics and knee co-contraction all increased with step length, but older non-fallers and fallers utilized greater stepping hip and less stepping knee extensor kinetics. Fallers had greater stepping knee co-contraction than non-fallers. Stance knee co-contraction of non-fallers was similar to young for shorter steps and similar to fallers for longer steps. Interpretation: Age had minimal effects and fall history had no effects on joint kinetics of steps to similar distances. Effects of age and fall history on knee co-contraction may contribute to age-related kinetic differences and shorter maximal step lengths of older non-fallers and fallers, but step length correlated with every variable tested. Thus, declines in maximum step length could indicate declines in hip and knee extensor kinetics and impaired performance on similar tasks like recovering from a trip. [Copyright &y& Elsevier]