The assessment of sarcopenia and the frailty phenotype in the outpatient care of older people: implementation and typical values obtained from the Newcastle SarcScreen project.

PURPOSE: Sarcopenia and the frailty phenotype both indicate older adults at risk of adverse health outcomes and yet are not widely assessed in practice. We developed the Newcastle SarcScreen to enable assessment of these two ageing syndromes during clinical care. In the setting of our Older People's Medicine Day Unit, our aims were to describe the implementation of the SarcScreen and to examine the typical values obtained. METHODS: The SarcScreen comprised height, weight, questions (three on the Fried frailty phenotype and five on the SARC-F questionnaire), grip strength and gait speed. We analysed data from 552 patients completing the SarcScreen. We expressed grip strength as Z-scores (number of standard deviations above the mean expected for a patient's age and sex). RESULTS: It was possible to implement the SarcScreen. In 552 patients (65.9% females) with mean age 80.1 (7.7) years, grip strength was feasible in 98.2% and gait speed in 82.1%. Gait speed was typically not assessed due to mobility impairment. Most patients had weak grip strength (present in 83.8%), slow gait speed (88.8%) and the frailty phenotype (66.2%). We found a high prevalence of probable sarcopenia and the frailty phenotype across all age groups studied. This was reflected by low grip strength Z-scores, especially at younger ages: those aged 60-69 had grip strength 2.7 standard deviations (95% CI 2.5-2.9) below that expected. CONCLUSION: It is possible to implement an assessment of sarcopenia and the frailty phenotype as part of the routine outpatient care of older people.

Detection of rotavirus in paediatric oncology patients with diarrhoea: the impact of rotavirus vaccine.

Seven years' data were reviewed to examine stool-testing for rotavirus in patents treated in a regional paediatric oncology unit before and after the introduction of UK-wide rotavirus immunization in July 2013. The prevalence of rotavirus positivity has diminished since the introduction of rotavirus immunization, with 21 of 416 positive samples between 2010 and 2012, but only one positive test out of 122 samples in 2015 and 2016. Based on these results, there seems to be little use for routine rotavirus-testing in children and young people with cancer presenting with diarrhoea.

Quantitative genetic study of the adaptive process.

The additive genetic variance with respect to absolute fitness, VA(W), divided by mean absolute fitness, , sets the rate of ongoing adaptation. Fisher's key insight yielding this quantitative prediction of adaptive evolution, known as the Fundamental Theorem of Natural Selection, is well appreciated by evolutionists. Nevertheless, extremely scant information about VA(W) is available for natural populations. Consequently, the capacity for fitness increase via natural selection is unknown. Particularly in the current context of rapid environmental change, which is likely to reduce fitness directly and, consequently, the size and persistence of populations, the urgency of advancing understanding of immediate adaptive capacity is extreme. We here explore reasons for the dearth of empirical information about VA(W), despite its theoretical renown and critical evolutionary role. Of these reasons, we suggest that expectations that VA(W) is negligible, in general, together with severe statistical challenges of estimating it, may largely account for the limited empirical emphasis on it. To develop insight into the dynamics of VA(W) in a changing environment, we have conducted individual-based genetically explicit simulations. We show that, as optimizing selection on a trait changes steadily over generations, VA(W) can grow considerably, supporting more rapid adaptation than would the VA(W) of the base population. We call for direct evaluation of VA(W) and in support of prediction of rates adaptive evolution, and we advocate for the use of aster modeling as a rigorous basis for achieving this goal.

No impairment of monocyte-derived Langerhans cell phenotype or function in early-onset psoriasis.

BACKGROUND: Migration of epidermal Langerhans cells (LCs) in response to the cytokines interleukin (IL)-1ß and tumour necrosis factor (TNF)-α is impaired in uninvolved skin of patients with early-onset psoriasis. AIM: To investigate whether this impairment is a reflection of a systemic defect in dendritic cells (DCs), using an established model of monocyte-derived LC-like cells (mLCs). METHODS: CD14+ monocytes isolated from both patients with psoriasis and healthy control volunteers were cultured in a cytokine cocktail for 5 days to promote their differentiation into mLCs, then stimulated for 24 h with TNF-α, IL-1ß (both 100 ng/mL) or medium alone. Cellular surface protein expression was quantified by flow cytometry, and the ability of cells to migrate to media supplemented with C-C motif ligand (CCL)19 was assessed using a Transwell migration assay. The cytokine and chemokine content of supernatants was analysed by cytokine array. RESULTS: CD14+ cells acquired an LC-like phenotype with high expression of CD1a and major histocompatibility complex (MHC) class II. There were no differences in the expression of activation markers or in the secretion of cytokines by mLCs isolated from patients with psoriasis and those isolated from healthy controls. Moreover, mLCs isolated from both groups displayed comparable ability to migrate in vitro. CONCLUSIONS: These data suggest that the failure of LCs to migrate in response to stimulation in patients with psoriasis is not attributable to a systemic defect in DC function, but is rather a reflection of local changes in the epidermal microenvironment.

Wireless and batteryless biomedical microsystem for neural recording and epilepsy suppression based on brain focal cooling.

This work presents a biomedical microsystem with a wireless radiofrequency (RF)-powered electronics and versatile sensors/actuators for use in nanomedicinal diagnosis and therapy. The cooling of brain tissue has the potential to reduce the frequency and severity of epilepsy. Miniaturised spiral coils as a wireless power module with low-dropout linear regulator circuit convert RF signals into a DC voltage, can be implanted without a battery in monitoring free behaviour. A thermoelectric (TE) cooler is an actuator that is employed to cool down brain tissue to suppress epilepsy. Electroencephalogram (EEG) electrodes and TE coolers are integrated to form module that is placed inside the head of a rat and fastened with a bio-compatible material. EEG signals are used to identify waveforms associated with epilepsy and are measured using readout circuits. The wireless part of the presented design achieves a low quiescent current and line/load regulation and high antenna/current efficiency with thermal protection to avoid damage to the implanted tissue. Epilepsy is suppressed by reducing the temperature to reduce the duration of this epileptic episode. Related characterisations demonstrate that the proposed design can be adopted in an effective nanomedicine microsystem.

Fitness-dependent mutation rates in finite populations.

Mutation rate may be condition dependent, whereby individuals in poor condition, perhaps from high mutation load, have higher mutation rates than individuals in good condition. Agrawal (J. Evol. Biol.15, 2002, 1004) explored the basic properties of fitness-dependent mutation rate (FDMR) in infinite populations and reported some heuristic results for finite populations. The key parameter governing how infinite populations evolve under FDMR is the curvature (k) of the relationship between fitness and mutation rate. We extend Agrawal's analysis to finite populations and consider dominance and epistasis. In finite populations, the probability of long-term existence depends on k. In sexual populations, positive curvature leads to low equilibrium mutation rate, whereas negative curvature results in high mutation rate. In asexual populations, negative curvature results in rapid extinction via 'mutational meltdown', whereas positive curvature sometimes allows persistence. We speculate that fitness-dependent mutation rate may provide the conditions for genetic architecture to diverge between sexual and asexual taxa.

Depression- and anxiety-like behaviors of a rat model with absence epileptic discharges.

Depression and/or anxiety are major comorbidities of epilepsy. However, the contribution of absence epileptic discharges in psychiatric syndromes is inconclusive. This study aimed to clarify the influence of absence seizure in anxiety- and depression-like behaviors using normal Wistar rats and Long-Evans rats with spontaneous spike-wave discharges (SWDs). Anxiety-like behaviors were evaluated by the open field (OF) and elevated plus maze (EPM) tests, and depression-like behaviors by the forced swimming (FS) and sucrose consumption (SC) tests. Long-Evans rats displayed significantly higher frequency and longer duration in the open arms of the EPM and in the center zone of the OF than did Wistar rats. Normalized behavioral indexes by movement also were significantly higher in Long-Evans rats. An excess of SWD numbers was associated with lower indexes and worse movement in the two behavioral tests. Ethosuximide eliminated the seizure frequency-dependent relationship and also significantly increased all indexes of the EPM test. Additionally, Long-Evans rats revealed significantly longer immobility in the FS test and lower consumption of sucrose solution in the SC test than did Wistar rats. Meanwhile, no relationship was found between immobility of the FS test and SWD number. Ethosuximide ameliorated depression-like behavior of Long-Evans rats that was equal to that of Wistar rats. Thus, Long-Evans rats showed seizure frequency-related exacerbation in anxiety-like behavior; and they displayed a depressive propensity. Our data suggest that generalized SWDs may have distinct influences in anxious and depressive behaviors.

Effects of age and gender on intravenous midazolam premedication: a randomized double-blind study.

BACKGROUND: Given the potentially important effects that age and gender may have on midazolam premedication, this study aimed at determining if these factors alter anxiety, sedation, and cardiorespiratory outcomes when administering two different doses of i.v. midazolam. METHODS: After randomization, patients were premedicated 1 h before surgery with either i.v. midazolam 0.02 or 0.06 mg kg(-1) depending on their age and gender group. Levels of anxiety and sedation, heart rate, respiratory rate (RR), mean blood pressure (MBP), and oxygen saturation (Sp(O2)) were measured before and 15 min after midazolam administration. RESULTS: A higher level of preoperative anxiety was more often observed in women than in men, and in young than in older patients. The female or younger patients showed significant anxiolytic benefits from midazolam. A deeper sedation level was found in men compared with women. Forty-two of 45 patients (93.3%) with excessive sedation received midazolam 0.06 mg kg(-1). The elderly patients receiving midazolam 0.06 mg kg(-1) showed significant reductions in MBP, RR, and Sp(O2). Of the patients with an Sp(O2)<90%, 72.7% had received midazolam 0.06 mg kg(-1). CONCLUSIONS: Age and gender differences in neuropsychological and physiological responses after midazolam premedication were evident. Midazolam is effective for producing sedation and anxiolysis at a dose of 0.02 mg kg(-1), with minimal effects on cardiorespiration and oxygen saturation to patients. Dosage adjustments based on these covariates are, therefore, necessary.

Migration load in plants: role of pollen and seed dispersal in heterogeneous landscapes.

Evolution of local adaptation depends critically on the level of gene flow, which, in plants, can be due to either pollen or seed dispersal. Using analytical predictions and individual-centred simulations, we investigate the specific influence of seed and pollen dispersal on local adaptation in plant populations growing in patchy heterogeneous landscapes. We study the evolution of a polygenic trait subject to stabilizing selection within populations, but divergent selection between populations. Deviations from linkage equilibrium and Hardy-Weinberg equilibrium make different contributions to genotypic variance depending on the dispersal mode. Local genotypic variance, differentiation between populations and genetic load vary with the rate of gene flow but are similar for seed and pollen dispersal, unless the landscape is very heterogeneous. In this case, genetic load is higher in the case of pollen dispersal, which appears to be due to differences in the distribution of genotypic values before selection.

Prevention of falls in older people with dementia.

Falls are a major cause of morbidity and mortality in older people with dementia. However, although we know that people with dementia can comply with interventions known to reduce falls in cognitively normal populations, and that these interventions can modify certain risk factors for falls in patients with dementia, direct evidence that falls can be prevented in older people with dementia is lacking. Further research is required specifically targeting fall prevention in older people with dementia.

Law and public health at CDC.

Public health law is an emerging field in U.S. public health practice. The 20th century proved the indispensability of law to public health, as demonstrated by the contribution of law to each of the century's 10 great public health achievements. Former CDC Director Dr. William Foege has suggested that law, along with epidemiology, is an essential tool in public health practice. Public health laws are any laws that have important consequences for the health of defined populations. They derive from federal and state constitutions; statutes, and other legislative enactments; agency rules and regulations; judicial rulings and case law; and policies of public bodies. Government agencies that apply public health laws include agencies officially designated as "public health agencies," as well as health-care, environmental protection, education, and law enforcement agencies, among others.

Prevalence of ballooning of the severed carotid arteries at slaughter in cattle, calves and sheep.

Previous work in calves indicated that ballooning of the severed arteries is a potential concern in animals receiving a reversible stun before slaughter, and in animals not stunned before slaughter, as it could extend the duration of brain function before the animals die. This study determined the prevalence of ballooning of the carotid arteries in a total of 987 cattle, calves and lambs at slaughter. The severed ends of the carotid arteries were examined by palpation. The prevalence of ballooning that was 3cm or more in diameter, was 16%, 25% and 0% for cattle, calves and lambs, respectively. Artery sections were taken from a sample of large cattle and examined histologically. In ballooned arteries there was coagulated blood between the outer surface of the artery and the inner aspect of the connective tissue sheath surrounding the artery, suggesting the formation of a false aneurysm in the ballooning phenomenon.

Carotid sinus syndrome is common in dementia with Lewy bodies and correlates with deep white matter lesions.

BACKGROUND: Carotid sinus syndrome (CSS) is a common cause of syncope in older persons. There appears to be a high prevalence of carotid sinus hypersensitivity (CSH) in patients with dementia with Lewy bodies (DLB) but not in Alzheimer's disease. OBJECTIVE: To compare the prevalence of CSH in DLB and Alzheimer's disease, and to determine whether there is an association between CSH induced hypotension and brain white matter hyperintensities on magnetic resonance imaging (MRI). METHODS: Prevalence of CSH was compared in 38 patients with DLB (mean (SD) age, 76 (7) years), 52 with Alzheimer's disease (80 (6) years), and 31 case controls (73 (5) years) during right sided supine carotid sinus massage (CSM). CSH was defined as cardioinhibitory (CICSH; >3 s asystole) or vasodepressor (VDCSH; >30 mm Hg fall in systolic blood pressure (SBP)). T2 weighted brain MRI was done in 45 patients (23 DLB, 22 Alzheimer). Hyperintensities were rated by the Scheltens scale. RESULTS: Overall heart rate response to CSM was slower (RR interval = 3370 ms (640 to 9400)) and the proportion of patients with CICSH greater (32%) in DLB than in Alzheimer's disease (1570 (720 to 7800); 11.1%) or controls (1600 (720 to 3300); 3.2%) (p<0.01)). The strongest predictor of heart rate slowing and CSH was a diagnosis of DLB (Wald 8.0, p<0.005). The fall in SBP during carotid sinus massage was greater with DLB (40 (22) mm Hg) than with Alzheimer's disease (30 (19) mm Hg) or controls (24 (19) mm Hg) (both p<0.02). Deep white matter hyperintensities were present in 29 patients (64%). In DLB, there was a correlation between magnitude of fall in SBP during CSM and severity of deep white matter changes (R = 0.58, p = 0.005). CONCLUSIONS: Heart rate responses to CSM are prolonged in patients with DLB, causing hypotension. Deep white matter changes from microvascular disease correlated with the fall in SBP. Microvascular pathology is a key substrate of cognitive impairment and could be reversible in DLB where there are exaggerated heart rate responses to carotid sinus stimulation.

How reproducible is the cardioinhibitory response to carotid sinus massage in fallers?

AIMS: To ascertain the reproducibility of the cardioinhibitory subtype of carotid sinus hypersensitivity (CICSH) in fallers. METHODS AND RESULTS: One hundred and seventy-five subjects with CICSH and unexplained or recurrent falls were randomized to pacemaker implantation or control. Sixty-four control subjects (61% female, mean age 71.8 years, median 2 falls in the previous year) completed one-year follow-up and had carotid sinus massage (CSM) performed on 4 occasions (twice before randomization, at 6 months and 1 year following randomization). CSM was performed sequentially on the right and then left sides, initially supine and then upright at 70 degrees head-up tilt by the same investigator. On each occasion CSM was discontinued once CICSH was demonstrated. CICSH was demonstrated on 82% of occasions, 75% on right CSM and 77% whilst the subject was supine. Before randomization, and at 6 months and 1 year, 91%, 67%, and 70% of subjects had reproducible CICSH respectively. Half had CICSH on all 4 occasions. Only 17% had a consistent response on the same side in the same position. CONCLUSIONS: In the majority of subjects CICSH is reproducible and this is more likely shortly after the initial response. However the cardioinhibitory response to CSM is inconsistent both in side elicited and subject position.

Carotid sinus syndrome: a modifiable risk factor for nonaccidental falls in older adults (SAFE PACE).

OBJECTIVES: The aim of the study was to determine whether cardiac pacing reduces falls in older adults with cardioinhibitory carotid sinus hypersensitivity (CSH). BACKGROUND: Cardioinhibitory carotid sinus syndrome causes syncope, and symptoms respond to cardiac pacing. There is circumstantial evidence for an association between falls and the syndrome. METHODS: A randomized controlled trial was done of consecutive older patients (>50 years) attending an accident and emergency facility because of a non-accidental fall. Patients were randomized to dual-chamber pacemaker implant (paced patients) or standard treatment (controls). The primary outcome was the number of falls during one year of follow-up. RESULTS: One hundred seventy-five eligible patients (mean age 73 +/- 10 years; 60% women) were randomized to the trial: pacemaker 87; controls 88. Falls (without loss of consciousness) were reduced by two-thirds: controls reported 669 falls (mean 9.3; range 0 to 89), and paced patients 216 falls (mean 4.1; range 0 to 29). Thus, paced patients were significantly less likely to fall (odds ratio 0.42; 95% confidence interval: 0.23, 0.75) than were controls. Syncopal events were also reduced during the follow-up period, but there were much fewer syncopal events than falls-28 episodes in paced patients and 47 in controls. Injurious events were reduced by 70% (202 in controls compared to 61 in paced patients). CONCLUSIONS: There is a strong association between non-accidental falls and cardioinhibitory CSH. These patients would not usually be referred for cardiovascular assessment. Carotid sinus hypersensitivity should be considered in all older adults who have non-accidental falls.

Diagnosing children presenting with asymmetric pendular nystagmus.

Horizontal asymmetric nystagmus usually occurs in one of three situations: secondary to an intracranial lesion, with monocular visual loss, or as part of the triad that constitutes the diagnosis of spasmus nutans (asymmetric nystagmus, abnormal head posture, head shake). Clinical records of 277 children, presenting with congenital nystagmus over an 8-year period were reviewed. Nystagmus was asymmetric in 24 of 277 cases. Seven of these patients were diagnosed with spasmus nutans. This is a rare condition that is only diagnosed retrospectively based on the absence of any abnormal neuroimaging or electrophysiological findings. Twelve of 24 patients had intracranial pathology and all had abnormal visual evoked potentials (VEPs). Five patients were diagnosed with congenital sensory defect nystagmus including one with albinism, three with congenital cone dysfunction, and one with cone-rod dystrophy. This paper stresses that although neuroimaging is necessary in all patients presenting with asymmetric nystagmus, such nystagmus can also occur with retinal disease or albinism and indicates the importance of non-invasive VEP/ERG testing in all forms of nystagmus.

Dynamic changes of touch- and laser heat-evoked field potentials of primary somatosensory cortex in awake and pentobarbital-anesthetized rats.

In this investigation, changes of mechanical- (MEP) and laser-evoked potentials (LEP) in rat primary somatosensory cortex during the course of pentobarbital (PB) anesthesia were examined. Temporal analysis of changes in the magnitude and latency of MEP and LEP, EEG activity, gross motor behaviors, and the tail flick response following laser stimulation before, during, and after PB administration (50 mg/kg, i.p.) was performed and correlated in chronically implanted rats. During the wakeful condition, there were two major cortical components each following mechanical stimulation (MEP1 and MEP2, n=17) and laser stimulation (LEP1 and LEP2, n=10), respectively. After PB administration, the positive peak in MEP1 was enhanced, and all other components disappeared. These components returned with different time courses. Two hours after PB administration, when the rat had spontaneous movements and flexor reflexes, LEP2 showed reversed polarity. MEP2 returned gradually 3 h after PB administration when the rat regained its ability to execute coordinated movements. After 4 h, LEP1 began to reappear and LEP2 returned to its negative polarity. We found that PB facilitated Abeta fiber-related cortical evoked potential (MEP1), while differentially inhibited Adelta and C fiber-related components (MEP2, LEP1 and LEP2). Characterization of these anesthesia-induced changes in cortical output may be useful in studying the neural basis of tactile and pain sensations.

[Cerebrovascular accident and its impact on clients, their partners, the couple's relationship]. / L'AVC et ses conséquences sur le client, son conjoint et la relation de couple.

The purpose of this study was to examine how stroke in one partner affects the personal well-being of the other partner and the couple's relationship. Six couples were followed throughout the rehabilitation period in the rehabilitation center and community setting. Study findings revealed that following the stroke, both patients and their spouses needed to redefine who they were and then redefine their couple relationship. The patients had to adapt to changes in their body and it's functioning. For the spouses, the need to redefine who they were was related to changes in their roles and responsibilities. For the couple, the need to redefine the relationship was related to the changes in both partners. The results of this study suggest that nurses consider the effects of stroke on the patient, the spouse, and the couple relationship and focus nursing interventions that facilitate the need to redefine themselves within the context of change.

Complications of carotid sinus massage--a prospective series of older patients.

BACKGROUND: there is a causal association between carotid sinus hypersensitivity, falls and syncope in elderly subjects. Neurological complications during carotid sinus massage have been reported in case studies and two retrospective series. Our aim was prospectively to ascertain the incidence of complications occurring after carotid sinus massage performed for diagnostic purposes in a consecutive series of patients. METHODS: 1000 consecutive subjects aged 50 years or over who attended the accident and emergency department with syncope or 'unexplained' falls had carotid sinus massage. Carotid sinus massage was performed for 5 s on the right and then left sides both supine and upright (70 degrees head-up tilt) with continuous heart rate and phasic blood pressure recording. Contraindications to carotid sinus massage were the presence of a carotid bruit, recent history of stroke or myocardial infarction or previous ventricular tachyarrhythmia. RESULTS: complications occurred in nine patients immediately after cessation of carotid sinus massage. Eight had transient neurological complications possibly attributable to carotid sinus massage: visual disturbance, 'pins and needles' and sensation of finger numbness in two cases each, leg weakness in one and sensation of 'being drunk' in one. All transient complications resolved within 24 h. In one patient mild weakness of the right hand persisted. CONCLUSIONS: no subjects had cardiac complications and 1% had possible neurological symptoms, which resolved in most cases. Persistent neurological complications are uncommon, occurring in 1:1000 patients (0.1%) or 1: 3805 episodes of carotid sinus massage (0.03%).