Managing the transition to non-driving in patients with dementia in primary care settings: facilitators and barriers reported by primary care physicians.

OBJECTIVES: This research addresses dementia and driving cessation, a major life event for affected individuals, and an immense challenge in primary care. In Australia, as with many other countries, it is primarily general practitioners (GPs) who identify changes in cognitive functioning and monitor driving issues with their patients with dementia. Qualitative evidence from studies with family members and other health professionals shows it is a complicated area of practice. However we still know little from GPs about how they manage the challenges with their patients and the strategies that they use to facilitate driving cessation. METHODS: Data were collected through five focus groups with 29 GPs at their primary care practices in metropolitan and regional Queensland, Australia. A semi-structured topic guide was used to direct questions addressing decision factors and management strategies. Discussions were audio recorded, transcribed verbatim and thematically analyzed. RESULTS: Regarding the challenges of raising driving cessation, four key themes emerged. These included: (i) Considering the individual; (ii) GP-patient relationships may hinder or help; (iii) Resources to support raising driver retirement; and (iv) Ethical dilemmas and ethical considerations. The impact of discussing driving cessation on GPs is discussed. CONCLUSIONS: The findings of this study contribute to further understanding the experiences and needs of primary care physicians related to managing driving retirement with their patients with dementia. Results support a need for programs regarding identification and assessment of fitness to drive, to upskill health professionals and particularly GPs to manage the complex issues around dementia and driving cessation, and explore cost-effective and timely delivery of such support to patients.

Immediate postpartum neurological deficits in the lower extremity: a prospective observational study.

BACKGROUND: Neurological deficits noted immediately after childbirth are usually various obstetric neuropathies, but prospective studies are limited. The main study aim was to quantify and describe immediate postpartum neurological deficits of the lower extremity, including the buttocks. METHODS: A prospective observational study of postpartum women delivering in a single maternity hospital during three months of 2016. Among 1147 eligible women, 1019 were screened for symptoms of lower extremity numbness or weakness within eight to 32hours of delivery. Consent to undergo a detailed neurological evaluation was sought from those reporting symptoms. Risk factors were identified using logistic regression. RESULTS: Thirty five women (3.4%) reported symptoms, 27 entered the study and 23 (2.0%) had objective signs of a neurological deficit. The most common injuries were mild lumbosacral plexopathies and cluneal nerve compression. Most deficits were sensory, half of these also having a motor deficit that did not impact functionally. Based on analysis of 22 cases involving a likely intrapartum deficit, no association was found with parity, body weight, duration of labour, mode of delivery or neuraxial block. A past history of a neurological condition or a back injury was associated with odds ratios of 7.98 and 4.82 respectively. There were no neurological deficits that were clinically concerning or that were likely a complication of a neuraxial block. CONCLUSION: Transient neurological complications after labour and delivery are infrequent, mainly sensory involving multiple lumbosacral nerve roots or specific sacral cutaneous nerves, and they typically resolve within a short time.

Risk assessment of wandering behavior in mild dementia.

OBJECTIVE: This prospective longitudinal study aims to determine the risk factors of wandering-related adverse consequences in community-dwelling persons with mild dementia. These adverse consequences include negative outcomes of wandering (falls, fractures, and injuries) and eloping behavior. METHODS: We recruited 143 dyads of persons with mild dementia and their caregivers from a veteran's hospital and memory clinic in Florida. Wandering-related adverse consequences were measured using the Revised Algase Wandering Scale - Community Version. Variables such as personality (Big Five Inventory), behavioral response to stress, gait, and balance (Tinetti Gait and Balance), wayfinding ability (Wayfinding Effectiveness Scale), and neurocognitive abilities (attention, cognition, memory, language/verbal skills, and executive functioning) were also measured. Bivariate and logistic regression analyses were performed to assess the predictors of these wandering-related adverse consequences. RESULTS: A total of 49% of the study participants had falls, fractures, and injuries due to wandering behavior, and 43.7% demonstrated eloping behaviors. Persistent walking (OR = 2.6) and poor gait (OR = 0.9) were significant predictors of negative outcomes of wandering, while persistent walking (OR = 13.2) and passivity (OR = 2.55) predicted eloping behavior. However, there were no correlations between wandering-related adverse consequences and participants' characteristics (age, gender, race, ethnicity, and education), health status (Charlson comorbidity index), or neurocognitive abilities. CONCLUSION: Our results highlight the importance of identifying at-risk individuals so that effective interventions can be developed to reduce or prevent the adverse consequences of wandering.

Interferencia de la tiroglobulina en la determinación de anticuerpos antitiroglobulina en el líquido de lavado de aguja de punción ganglionar / Thyroglobulin Interference in the Determination of Thiroglobulin Antibody in Wash-Out Fluid from Fine Needle Aspiration Biopsy of Lymph Node

La interferencia producida por los anticuerpos antitiroglobulina (aTg) en la determinación de Tiroglobulina (Tg) ha sido bien estudiada, sin embargo la interferencia que puede producir esta última sobre la determinación de los anticuerpos no está clara. Objetivo: Investigar la interferencia que la Tg puede producir sobre la determinación de los aTg en el líquido de lavado de aguja de punción ganglionar. Material y Métodos: Se estudiaron retrospectivamente las muestras provenientes de la punción de adenopatías cervicales sospechosas de 19 pacientes tiroidectomizados por Cáncer Diferenciado de Tiroides (CDT). La punción se realizó con aguja 22 G bajo guía ecográfica y luego de la preparación del extendido para el estudio citológico se procedió al lavado de la aguja con 500 µl de solución fisiológica para determinar Tg y aTg. La medición de Tg se hizo por ensayo quimioluminiscente. Los aTg se midieron utilizando dos ensayos uno no competitivo quimioluminiscente (Q) y otro competitivo electroquimioluminiscente (Eq). Se consideraron aTg negativos valores < 20 UI/ml. Se realizaron diluciones de la muestra de uno de los pacientes para el estudio de interferencia. Resultados: En todas las muestras las concentraciones de Tg mostraron valores muy elevados (rango: 15.185 -1.141.275 ng/ml). Los resultados de los aTg fueron negativos en el 100 % de las muestras cuando se midieron por el método no competitivo (Q) y francamente positivos en un rango de 106 a > 4.000 UI/ml cuando se midieron por el método competitivo (Eq), siendo estos valores proporcionales a la concentración de Tg en la muestra. Se observó una falta de linealidad cuando se realizó ensayo de dilución a muestras de concentración elevada de aTg medidas por Eq. Los aTg por Eq se negativizaron a concentraciones de Tg inferiores a 3.000 ng/ml. Los aTg medidos por Q arrojaron valores negativos en todas las diluciones. Todos estos pacientes presentaban aTg negativos en suero por Q y Eq. Conclusión: Las altas concentraciones de Tg interfieren en la medición de aTg cuando los mismos son medidos por un método competitivo. La interferencia es proporcional a las concentraciones de Tg presentes en la muestra. Se recomienda que en los líquidos de lavado de aguja de punción ganglionar los aTg sean medidos por un método no competitivo ya que no parece estar interferido por las altas concentraciones de Tg característica de los ganglios metastásicos. La detección de esta interferencia no modificó el diagnóstico ni la conducta clínica en ningún caso, sin embargo es importante conocerla con el fin de no concluir erróneamente sobre la positividad de los anticuerpos en los ganglios cuando estos son medidos por un ensayo competitivo. Rev Argent Endocrinol Metab 51:1-7, 2014 Los autores declaran no poseer conflictos de interés.

Thyroglobulin antibodies (TgAb) interference with thyroglobulin (Tg) measurements has been well studied; however, Tg interference with TgAb is unclear. Objective: To investigate how TgAb may interfere with Tg measurement in the washout fluid from lymph node fine-needle aspiration biopsy. Materials and Methods: We retrospectively studied the samples obtained by aspiration of suspicious cervical lymph nodes from 19 patients post thyroidectomy for Differentiated Thyroid Cancer (DTC). The puncture was performed with a 22 G needle under ultrasound guidance. After preparation of cytological specimens, the needle was washed with 500 ul of saline solution to determine Tg and TgAb. Tg was measured by chemilumi­nescent assay and TgAb was measured using two assays: a non-competitive chemiluminescent assay (Q) and a competitive electrochemiluminescence assay (Eq). Values of TgAb below 20 UI/ml were considered negative. Appropriate dilutions of the sample of one of the patients were performed in order to study interference. Results: In all samples tested, concentrations showed very high Tg values (range: 15.185 - 1.141.275 ng/ml). TgAb results were negative in all the samples measured by the non-competitive method. Results were clearly positive in a range of 106 to > 4.000 IU/ml when the competitive assay (Eq) was used, being proportional to Tg concentrations in the samples. A lack of linearity was observed when a dilution assay was performed in samples of high TgAb concentrations measured by Eq. When Tg concentrations were below 3.000 ng / ml, TgAb became negative when measured by Eq. TgAbs measured by Q were negative in all dilutions. TgAbs in serum were negative in all patients by the two methodologies (Q and Eq). Conclusion: High levels of Tg interfere with TgAb measurement when a competitive method is used. The interference is proportional to the concentrations of Tg. It is recommended that in the wash-out fluid from fine needle aspiration, TgAbs should be measured by a non-competitive method since there appears to be no interference from the high concentrations of Tg characteristic of metastatic nodes. The detection of this interference did not change the diagnosis or clinical management in any case; however, it is important to be aware of such interference so as not to make erroneous conclusions about the positivity of TgAbs in lymph nodes when a competitive method is used. Rev Argent Endocrinol Metab 51:1-7, 2014 No financial conflicts of interest exist.

Mapping a quantitative trait locus for the concentration of beta-lactoglobulin in milk, and the effect of beta-lactoglobulin genetic variants on the composition of milk from Holstein-Friesian x Jersey crossbred cows.

AIM: To identify quantitative trait loci (QTL) affecting the concentration of beta-lactoglobulin in milk, and to evaluate the effect of beta-lactoglobulin genetic variants on the concentration of fat, protein and casein in bovine milk. METHODS: A herd of 850 F2 Holstein-Friesian x Jersey crossbred cows was produced through mating six Holstein-Friesian x Jersey F1 bulls of high genetic merit with F1 cows from the national herd. A total of 1,610 herd-test records from 556 second-parity crossbreds were analysed. The concentration of fat, protein and casein in milk was measured at peak, mid- and late lactation, during the production seasons of 2003-2004 and 2004-2005. Liveweight was measured daily. DNA from the F2 animals, their F1 dams and sires, and selected grandsires was genotyped across the genome, initially with 285 microsatellite markers, and subsequently with 6,634 single nucleotide polymorphisms (SNP). RESULTS: A highly significant QTL for the concentration of beta-lactoglobulin in milk was identified, which coincided with the position of the beta-lactoglobulin gene on bovine Chromosome 11. No other consistently significant QTL for the concentration of beta-lactoglobulin in milk were detected. Cows with the BB beta-lactoglobulin genotype produced milk with a 30% lower concentration of beta-lactoglobulin than cows with the AA genotype. The beta-lactoglobulin polymorphism also explained variation in the proportion of casein in total protein. In addition, the percentage of fat was higher for BB than AA animals, whereas the percentage of total protein, mean daily milk yield and liveweight did not differ between AA and BB animals. CONCLUSIONS: A significant QTL determining the concentration of beta-lactoglobulin in milk was identified. Selection of animals for the beta-lactoglobulin B-allele may enable the production of milk naturally enriched for casein, thus allowing a potential increase in the yield of cheese. There may be additional future value in production of bovine milk more like human milk, where decreasing the concentration of beta-lactoglobulin is desirable.

Mutation in bovine beta-carotene oxygenase 2 affects milk color.

beta-Carotene biochemistry is a fundamental process in mammalian biology. Aberrations either through malnutrition or potentially through genetic variation may lead to vitamin A deficiency, which is a substantial public health burden. In addition, understanding the genetic regulation of this process may enable bovine improvement. While many bovine QTL have been reported, few of the causative genes and mutations have been identified. We discovered a QTL for milk beta-carotene and subsequently identified a premature stop codon in bovine beta-carotene oxygenase 2 (BCO2), which also affects serum beta-carotene content. The BCO2 enzyme is thereby identified as a key regulator of beta-carotene metabolism.

Evidence supporting nutritional interventions for persons in early stage Alzheimer's disease (AD).

The purpose of this paper is to grade research evidence supporting nutritional interventions for persons with early stage dementias and to report the recommendations of a consensus panel. Thirty four studies were reviewed in the areas of dietary restriction, antioxidants, and Mediterranean diet with strong support from epidemiological studies found in all three areas. The body of evidence to support nutritional interventions in the prevention and treatment of AD is growing and has potential as a treatment modality following translational studies.

Genetic screening protocol for familial hypercholesterolemia which includes splicing defects gives an improved mutation detection rate.

Familial hypercholesterolemia (FH) is a common single gene disorder, which predisposes to coronary artery disease. In a previous study, we have shown that in patients with definite FH around 20% had no identifiable gene defect after screening the entire exon coding area of the low density lipoprotein receptor (LDLR) and testing for the common Apolipoprotein B (ApoB) R3500Q mutation. In this study, we have extended the screen to additional families and have included the non-coding intron splice regions of the gene. In families with definite FH (tendon xanthoma present, n=68) the improved genetic screening protocol increased the detection rate of mutations to 87%. This high detection rate greatly enhances the potential value of this test as part of a clinical screening program for FH. In contrast, the use of a limited screen in patients with possible FH (n=130) resulted in a detection rate of 26%, but this is still of significant benefit in diagnosis of this genetic condition. We have also shown that 14% of LDLR defects are due to splice site mutations and that the most frequent splice mutation in our series (c.1845+11 c>g) is expressed at the RNA level. In addition, DNA samples from the patients in whom no LDLR or ApoB gene mutations were found, were sequenced for the NARC-1 gene. No mutations were identified which suggests that the role of NARC-1 in causing FH is minor. In a small proportion of families (<10%) the genetic cause of the high cholesterol remains unknown, and other genes are still to be identified that could cause the clinical phenotype FH.

Keeping wandering nursing home residents at the table: improving food intake using a behavioral communication intervention.

The purpose of this multiple case design study (n = 3) with an embedded experiment was to determine the effect of the systematic use of a behavioral nursing intervention on the mealtime behavior of nursing home residents with probable Alzheimer's disease. It was hypothesized that the systematic behavioral intervention would increase time spent seated during the meal and proportion of food consumed while decreasing the frequency of table-leaving events during mealtime. The intervention was designed to impact the proximal factors of physiological need and social interaction from the Need-Driven Behavior Model. Results demonstrate that all cases were able to sit at the table longer and eat more food during the intervention, while body weight for all cases remained stable throughout the study. Two of the three cases left the table fewer times during the intervention. There were no statistically significant changes in proportion of fluids consumed in any case.

Validation of the Algase Wandering Scale (Version 2) in a cross cultural sample.

This study examined the psychometric properties of an expanded version of the Algase Wandering Scale (Version 2) (AWS-V2) in a cross-cultural sample. A cross-sectional survey design was used. Study subjects were 172 English-speaking persons with dementia (PWD) from long-term care facilities in the USA, Canada, and Australia. Two or more facility staff rated each subject on the AWS-V2. Demographic and cognitive data (MMSE) were also obtained. Staff provided information on their own knowledge of the subject and of dementia. Separate factor analyses on data from two samples of raters each explained greater than 66% of the variance in AWS-V2 scores and validated four (persistent walking, navigational deficit, eloping behavior, and shadowing) of five factors in the original scale. Items added to create the AWS-V2 strengthened the shadowing subscale, failed to improve the routinized walking subscale, and added a factor, attention shifting as compared to the original AWS. Evidence for validity was found in significant correlations and ANOVAs between the AWS-V2 and most subscales with a single item indicator of wandering and with the MMSE. Evidence of reliability was shown by internal consistency of the AWS-V2 (0.87, 0.88) and its subscales (range 0.88 to 0.66), with Kappa for individual items (17 of 27 greater than 0.4), and ANOVAs comparing ratings across rater groups (nurses, nurse aids, and other staff). Analyses support validity and reliability of the AWS-V2 overall and for persistent walking, spatial disorientation, and eloping behavior subscales. The AWS-V2 and its subscales are an appropriate way to measure wandering as conceptualized within the Need-driven Dementia-compromised Behavior Model in studies of English-speaking subjects. Suggestions for further strengthening the scale and for extending its use to clinical applications are described.

A Delphi study to identify performance indicators for emergency medicine.

OBJECTIVES: The aim of this study was to identify performance indicators thought to reflect the quality of patient care in the emergency department. METHODS: A three round accelerated Expert Delphi study was conducted by email or fax. A panel of 33 experts drawn from the fields of emergency medicine, emergency nursing, professional service users, and patients were consulted. Participants were initially asked to propose performance indicators that reflected the quality of care given in the emergency department setting in the United Kingdom. In the second round these proposals were collated and scored using a 9 point Likert scale; those that had not reached consensus were returned for reconsideration in the light of group opinion. Those statements reaching a pre-defined consensus were identified. RESULTS: 224 performance indicators were proposed. Altogether 36 indicators reached consensus reflecting good departmental performance after round three; 24 of these were process measures. CONCLUSIONS: 36 potential indicators of good quality of care in the emergency department in the UK have been identified.

The Algase Wandering Scale: initial psychometrics of a new caregiver reporting tool.

This paper reports on the Algase wandering scale (AWS), a 28-item questionnaire, based on five dimensions of wandering. With factor analysis, an eight-factor solution explained nearly 70 percent of the variance in ratings for 151 long-term care subjects and confirmed three of the structuring dimensions. Reliability of the AWS was examined for internal consistency and for inter-rater reliability. The AWS had an alpha of .86; subscale alphas ranged between .88 (persistent walking) and .57 (routinized walking). Inter-rater reliabilities, estimated through cross-rater comparisons of the AWS and subscales with a four-point judgement of wandering status, were moderately strong and no significant differences existed between two sets of raters. Validity of the AWS and its subscales was supported by examining their ability to differentiate wanderers and nonwanderers, by positive correlation with measures of cognitive impairment and with multiple parameters of observed wandering, and by negative or no correlations with nonwandering locomotion. Although the AWS may be a useful measure of wandering in long-term care settings, validation of its factor structure and evaluation in cross-cultural samples is needed.

Role of AMPA receptor endocytosis in synaptic plasticity.

Activity-mediated changes in the strength of synaptic communication are important for the establishment of proper neuronal connections during development and for the experience-dependent modification of neural circuitry that is believed to underlie all forms of behavioural plasticity. Owing to the wide-ranging significance of synaptic plasticity, considerable efforts have been made to identify the mechanisms by which synaptic changes are triggered and expressed. New evidence indicates that one important expression mechanism of several long-lasting forms of synaptic plasticity might involve the physical transport of AMPA-type glutamate receptors in and out of the synaptic membrane. Here, we focus on the rapidly accumulating evidence that AMPA receptors undergo regulated endocytosis, which is important for long-term depression.

Impact of cognitive impairment on wandering behavior.

The purpose of this study was to explore cognitive impairment as a predictor of wandering rhythm and pattern in a sample of 25 demented residents from two long-term care settings. Parameters of rhythm indicating cycle frequency and structure were examined for wandering patterns (random, lapping, and pacing) and for nonwandering (direct) ambulation. All measures of cognitive impairment (Mini-Mental State Exam, Mattis Dementia Rating Scale, and a neuropsychologist's clinical rating) were significant predictors of parameters signifying frequency of wandering for random and lapping patterns but not for the pacing pattern. In addition, for nonwandering ambulation, cognitive impairment predicted some parameters of cycle structure (mean locomoting and nonlocomoting phase durations) but not those denoting frequency of ambulation. Results indicate that cognitive impairment plays an important role in determining the frequency of wandering cycles, but other factors may better explain parameters that characterize its cycle structure.

Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD.

The endocytosis of AMPA receptors is thought to be important in the expression of long-term depression (LTD) triggered by NMDA receptor activation. Although signaling pathways necessary for LTD induction have been identified, those responsible for the regulated internalization of AMPA receptors are unknown. Here we show that activation of NMDA receptors alone can trigger AMPA receptor endocytosis through calcium influx and activation of the calcium-dependent protein phosphatase calcineurin. A distinct signaling mechanism mediates the AMPA receptor endocytosis stimulated by insulin. These results demonstrate that although multiple signaling pathways can induce AMPA receptor internalization, NMDA receptor activation enhances AMPA receptor endocytosis via a signaling mechanism required for the induction of LTD.

NGF signals through TrkA to increase clathrin at the plasma membrane and enhance clathrin-mediated membrane trafficking.

Neurotrophin (NT) signals may be moved from axon terminals to neuron cell bodies via signaling endosomes-organelles in which NTs continue to be bound to their activated receptors. Suggesting that clathrin-coated membranes serve as one source of signaling endosomes, in earlier studies we showed that nerve growth factor (NGF) treatment increased clathrin at the plasma membrane and resulted in colocalization of clathrin with TrkA, the receptor tyrosine kinase for NGF. Strikingly, however, we also noted that most clathrin puncta at the surface of NGF-treated cells did not colocalize with TrkA, raising the possibility that NGF induces a general increase in clathrin-coated membrane formation. To explore this possibility further, we examined the distribution of clathrin in NGF- and BDNF-treated cells. NGF signaling in PC12 cells robustly redistributed the adaptor protein AP2 and the clathrin heavy chain (CHC) to surface membranes. Using confocal and epifluorescence microscopy, as well as biochemical assays, we showed the redistribution of clathrin to be attributable to the activation of TrkA. Significantly, NGF signaled through TrkA to induce an increase in clathrin-mediated membrane trafficking, as revealed in the increased endocytosis of transferrin. In that BDNF treatment increased AP2 and clathrin at the surface membranes of hippocampal neurons, these findings may represent a physiologically significant response to NTs. We conclude that NT signaling increases clathrin-coated membrane formation and clathrin-mediated membrane trafficking and speculate that this effect contributes to their trophic actions via the increased internalization of receptors and other proteins that are present in clathrin-coated membranes.

Gene transfer of endothelial nitric oxide synthase but not Cu/Zn superoxide dismutase restores nitric oxide availability in the SHRSP.

OBJECTIVE: Previous studies from our group have shown a deficit in nitric oxide (NO) bioavailability and an excess production of the superoxide anion (O(2)(-)) in the stroke prone spontaneously hypertensive rat (SHRSP) compared to the normotensive Wistar Kyoto (WKY) strain. This present study has investigated whether adenoviral-mediated gene transfer of human eNOS or Cu/ZnSOD can alter the NO/O(2)(-) balance, thereby improving endothelial function. METHODS: A recombinant adenovirus, Ad/Hu/eNOS, containing the human eNOS cDNA fragment was generated by homologous recombination in 293 cells. Ad/Hu/eNOS or Ad/Cu/ZnSOD was delivered into SHRSP carotid arteries in vivo, using a titre of 2x10(9)-2x10(10) plaque forming units (pfu)/ml, and the effect on gene expression was observed 24 h later. RESULTS: Western blotting confirmed increased enzyme levels of eNOS and Cu/ZnSOD in the viral-infused vessels. Ex vivo, the pressor response to phenylephrine (PE) in the presence of L-NAME was increased in the eNOS-infused arteries relative to the contralateral controls, indicating restoration of basal NO availability to that observed in untreated control WKY rats. Infusion of the SOD virus produced a statistically insignificant increase in NO bioavailability. CONCLUSIONS: Our results support our previous findings obtained using a bovine eNOS recombinant adenovirus, that recombinant adenoviral gene transfer of human eNOS has a significant effect on NO bioavailability. In contrast, AdCu/ZnSOD gene transfer does not elicit an effect in our model. These results indicate that short-term overexpression of a recombinant eNOS, but not Cu/ZnSOD gene, in carotid arteries of the SHRSP is an effective means of locally increasing NO bioavailability to improve endothelial function.

Tales from the crypt: evidence for heptahelical receptor signaling in the endocytic pathway.

In certain circumstances, internalized receptors are able to continue signaling after endocytosis. Whistler et al. discuss how the interaction of heterotrimeric GTP-binding protein (G protein)-coupled receptors with arrestins and their subsequent endocytosis may contribute to activation of the mitogen-activated protein kinase pathway. This perspective delves into the role that scaffolds may play in organizing and specifying downstream signaling events that occur after internalization of G protein-coupled receptors.