Sleep pressure modulates single-neuron synapse number in zebrafish.

Sleep is a nearly universal behaviour with unclear functions1. The synaptic homeostasis hypothesis proposes that sleep is required to renormalize the increases in synaptic number and strength that occur during wakefulness2. Some studies examining either large neuronal populations3 or small patches of dendrites4 have found evidence consistent with the synaptic homeostasis hypothesis, but whether sleep merely functions as a permissive state or actively promotes synaptic downregulation at the scale of whole neurons is unclear. Here, by repeatedly imaging all excitatory synapses on single neurons across sleep-wake states of zebrafish larvae, we show that synapses are gained during periods of wake (either spontaneous or forced) and lost during sleep in a neuron-subtype-dependent manner. However, synapse loss is greatest during sleep associated with high sleep pressure after prolonged wakefulness, and lowest in the latter half of an undisrupted night. Conversely, sleep induced pharmacologically during periods of low sleep pressure is insufficient to trigger synapse loss unless adenosine levels are boosted while noradrenergic tone is inhibited. We conclude that sleep-dependent synapse loss is regulated by sleep pressure at the level of the single neuron and that not all sleep periods are equally capable of fulfilling the functions of synaptic homeostasis.

Therapeutic use of compression stockings for orthostatic hypotension: an assessment of patient and physician perspectives and practices.

BACKGROUND: Elastic compression stockings (ECS) can be used as a non-pharmacological therapeutic option for older patients with orthostatic hypotension (OH). We aimed to investigate the practices and views of patients and physicians regarding the use of ECS for OH. METHODS: Two surveys were designed. The first was sent to 90 patients known to have been prescribed ECS for OH. This questionnaire included items related to the frequency of use and issues related to non-compliance. The second was sent to 69 consultant physicians in geriatric medicine. This included items related to prescribing practices and perceived patient compliance. RESULTS: Sixty-seven patients responded (response rate, 74%) and of those 64% were female. Mean age (SD) was 75.1 years (10.5), range 45-91 years. Thirty-three per cent wore ECS daily, whereas 43% never used them. Over half (51%) of the patients reported difficulty in application and 31% reported discomfort. Those aged 75 or older were more likely to report difficulty in application (P=0.003). Forty-eight physicians responded (response rate, 70%). Eighty-nine per cent prescribe ECS for OH. There were significant differences between the frequency of use reported by patients and predicted by physicians (P<0.001), with physicians less likely to predict daily or non-use. Eighty-nine per cent of physicians predicted that difficulty in application was the main reason for non-compliance. CONCLUSION: Although prescribed frequently, the use of ECS in patients with OH is often limited by issues related to practicality. Physicians correctly predicted the main reasons for non-compliance although underestimated the scale of patient compliance with ECS.

Point Prevalence Survey of Acute Hospital Patients with Difficulty Swallowing Solid Oral Dose Forms.

The safe administration of solid oral dose forms in hospital inpatients with swallowing difficulties is challenging. The aim of this study was to establish the prevalence of difficulties in swallowing solid oral dose forms in acute hospital inpatients. A point prevalence study was completed at three time points. The following data were collected: the prevalence of swallowing difficulties, methods used to modify solid oral dose forms to facilitate administration, the appropriateness of the modification, and patient co-morbidities. The prevalence of acute hospital inpatients with swallowing difficulties was an average of 15.4% with a 95% CI [13.4, 17.6] across the three studies. On average, 9.6% of patients with swallowing difficulties had no enteral feeding tube in situ, with 6.0% of these patients receiving at least one modified medicine. The most common method of solid oral dose form modification was crushing, with an administration error rate of approximately 14.4%. The most common co-morbid condition in these patients was hypertension, with dysphagia appearing on the problem list of two (5.5%) acute hospital inpatients with swallowing difficulties. Inappropriate modifications to solid oral dose forms to facilitate administration can result in patient harm. A proactive approach, such as the use of a screening tool to identify acute hospital inpatients with swallowing difficulties, is required, to mitigate the risk of inappropriate modifications to medicines to overcome swallowing difficulties.

The prevalence and pathological correlates of orthostatic hypotension and its subtypes when measured using beat-to-beat technology in a sample of older adults living in the community.

BACKGROUND: beat-to-beat technology is increasingly used for investigating orthostatic intolerance (OI) but the prevalence of orthostatic hypotension (OH) diagnosed with this technology is unclear. OBJECTIVES: (i) to use beat-to-beat technology to define the prevalence of OH, (ii) to investigate the pathological correlates of OH, (iii) to report the diversity of postural BP responses. METHODS: cross-sectional study of adults ≥ 65 years. BP responses to a 3-min head-up tilt were analysed. RESULTS: of 326 participants, 203(62.3%) were females. The median (IQR) age was 73 (70-78). One hundred and ninety-one (58.6%) met standard (20 mmHg systolic/10 mmHg diastolic) criteria for OH. The prevalence was higher in females (60.1% F versus 56.1% M); 47% were arteriolar subtype, 33% were venular, 9% were mixed and 11.0% could not be classified. Morphological analysis identified 102 subjects with 'small drop, overshoot', 131 with 'medium drop, slow recovery' and 31 with 'large drop, nonrecovery'. Those with OH had a lower BMI (P = 0.02), a higher resting heart rate (P = 0.005), were more likely to take a psychotropic (P = 0.02), have vertigo (P = 0.004) and report OI (P = 0.02). The 95th centile for the duration of systolic BP (SYSBP) decay >20 mmHg was 175 s and the slope of systolic BP decay was 4.75 mmHg/s. The 5th centile for percentage recovery of SYSBP was 81.4%. CONCLUSION: (i) beat-to-beat methods identify a higher prevalence of OH than sphygmomanometry, (ii) the pathological correlates of OH diagnosed in this manner are similar to those described for sphygmomanometry, (iii) there is a diverse pattern of orthostatic BP decay that could be used in future research to predict adverse outcomes in OH.

Noradrenergic tone is not required for neuronal activity-induced rebound sleep in zebrafish.

Sleep pressure builds during wakefulness, but the mechanisms underlying this homeostatic process are poorly understood. One zebrafish model suggests that sleep pressure increases as a function of global neuronal activity, such as during sleep deprivation or acute exposure to drugs that induce widespread brain activation. Given that the arousal-promoting noradrenergic system is important for maintaining heightened neuronal activity during wakefulness, we hypothesised that genetic and pharmacological reduction of noradrenergic tone during drug-induced neuronal activation would dampen subsequent rebound sleep in zebrafish larvae. During stimulant drug treatment, dampening noradrenergic tone with the α2-adrenoceptor agonist clonidine unexpectedly enhanced subsequent rebound sleep, whereas enhancing noradrenergic signalling with a cocktail of α1- and ß-adrenoceptor agonists did not enhance rebound sleep. Similarly, CRISPR/Cas9-mediated elimination of the dopamine ß-hydroxylase (dbh) gene, which encodes an enzyme required for noradrenalin synthesis, enhanced baseline sleep in larvae but did not prevent additional rebound sleep following acute induction of neuronal activity. Across all drug conditions, c-fos expression immediately after drug exposure correlated strongly with the amount of induced rebound sleep, but was inversely related to the strength of noradrenergic modulatory tone. These results are consistent with a model in which increases in neuronal activity, as reflected by brain-wide levels of c-fos induction, drive a sleep pressure signal that promotes rebound sleep independently of noradrenergic tone.

Adult Patients with Difficulty Swallowing Oral Dosage Forms: A Systematic Review of the Quantitative Literature.

The aim of this systematic review was to identify and critically appraise the available evidence regarding solid oral dosage forms (SODFs), e.g., tablets, and challenges regarding the oral administration of medicine to inpatients in a variety of healthcare settings such as (1) hospitals, (2) nursing homes and (3) long-term stay units (LTSUs). A literature search was undertaken in September 2021 and repeated in June 2023 in the following databases: PubMed, EMBASE, CINAHL, Scopus, Web of Science, The Cochrane Library, PsycINFO and ProQuest. A Microsoft Excel® spreadsheet was devised to collate the following data from each eligible study: study author and year, country, number of participants, title, duration (follow-up period), study design, inclusion and exclusion criteria, method and data collection, relevant outcomes, and key findings. A total of 3023 records were identified, with 12 articles being included in the final systematic review. Seven of the twelve studies reported on the prevalence of difficulties swallowing SODFs, which varied from 10-34.2%. Nine of the twelve studies reported the methods used to manipulate SODFs, with the most reported method being tablet crushing. Given the prevalence of swallowing difficulties and the subsequent crushing of medicines in response to this, it is evident that concerns should be raised regarding the potential for a medication administration error to occur.

Low dose hydrophilic statins are the preferred agents for females at risk of osteoporosis.

OBJECTIVES: The correlation between atherosclerosis and osteoporosis, independent of age, is clear. Multifactorial co-dependence between bone mineral density (BMD) and statin dose has been proposed. It is hypothesised that inhibition of the synthesis of cholesterol will also inhibit the synthesis of sex hormones and Vitamin D, negatively affecting BMD. This study aims to evaluate hydrophilic and non-hydrophilic statins effect on osteoporosis and analyse any possible superiority of one agent over the other within the group. METHODS: We identified 538 caucasian females who had a DEXA scan performed between 2002 and 2016 (age 60-89) in one DEXA center in Mid-West Ireland. A DEXA T-score results were analysed in the current study. Two hundred fifty females were not on statin therapy, and 323 females were on statin therapy. Females on therapy were separated into the atorvastatin group (N = 190), rosuvastatin group (N = 97), and pravastatin group (N = 36), comprising low dose and high dose groups. All anonymised data were analysed with SPSS statistical. To test the hypothesis that lower bone density is associated with high dose statins, an independent sample t-test was performed. The one-way between-groups ANOVA test was used to test the hypothesis that the BMD level depended on the statin's potency. RESULTS: Statin-naïve females have a statistically higher bone mineral density in the lumbar spine, t (538) = 3.42, p < 0.05 and in hip t (538) = 4.99, p < 0.05 than females on statin therapy. There was a significant difference in patient's age between the group, and no significant correlation was found between the patient's age and type of statin or bone density. In the atorvastatin group statistically, significant results were obtained both for spine and hip bone mineral density, t (188) = -5.61, p < 0.05 and t (188) = -3.62, p < 0.05, respectively. In the rosuvastatin group, statistically, a significant result was noted for bone mineral density of hip t (95) = -3.52, p < 0.05. This demonstrates a dose-dependency between bone mineral density and the dose of the statin. The independent between-group ANOVA yielded a statistically significant effect, F (2, 59) = 6.69, p < 0.05, η2 = 0.21 in the spine. Thus, patients on lipophilic statins had statistically lower BMD than females on hydrophilic statins. Multilinear regression analysis identified that age is not a statistically significant contributor in our analysis; however, the trend of decrease in bone mineral density with women's age is acknowledged by authors. CONCLUSIONS: The study results support the theory that bone mineral density decreases with an increase in a statin dose, and hydrophilic statins, like pravastatin, have a better metabolic profile in the lumbar spine than lipophilic agents.

Audit of inpatient acute stroke services in a university teaching hospital, 2020.

BACKGROUND: We aimed to assess stroke care at an Irish university teaching hospital and benchmark against national (Irish National Audit of Stroke 2019) and international (6th SSNAP Annual Report; American Heart Association, 2013) practice to inform a quality improvement strategy. METHODS: All patients with a HIPE discharge diagnosis of Cerebral Infarction or Cerebral Haemorrhage (1 January to 31 December 2019) were identified through both the HIPE database and the institutional Stroke Portal. RESULTS: A total of 419 patients were included (56.6% male, mean age 72). The following were comparable/better than findings from the Irish National Audit of Stroke: median duration of symptoms-3 h 6 min; 10% received thrombolysis; median door to needle time-60 min; 78.5% admitted to the stroke unit; 81.1% had a swallow assessment; in-patient mortality rate-10.5%; rates of institutionalisation-3.8%. The following areas were below the national average: overall door to imaging time-median 104 min; rate of thrombectomy-4%; 11.5% had mood screening; median length of stay- 12 days. DISCUSSION: Using national and international audit data as an institutional benchmark provides a standard with which a service can be compared to highlight areas for improvement. We identified mood screening, swallow screening, thrombectomy rates, length of stay and time to neuroimaging as key areas for development in our centre. We are currently completing a process map to determine cause, effect, and solutions, and we will implement change using PDSA methodology as per SQUIRE 2.0 guidelines. The results of the re-audit cycle for 2020 will be available in 2021 to inform our progress. Ongoing quality improvement is essential for stroke care, which is a leading cause of death and disability in Ireland.

Specialist medication review does not benefit short-term outcomes and net costs in continuing-care patients.

OBJECTIVES: to evaluate specialist geriatric input and medication review in patients in high-dependency continuing care. DESIGN: prospective, randomised, controlled trial. SETTING: two residential continuing care hospitals. PARTICIPANTS: two hundred and twenty-five permanent patients. INTERVENTION: patients were randomised to either specialist geriatric input or regular input. The specialist group had a medical assessment by a geriatrician and medication review by a multidisciplinary expert panel. Regular input consisted of review as required by a medical officer attached to each ward. Reassessment occurred after 6 months. RESULTS: one hundred and ten patients were randomised to specialist input and 115 to regular input. These were comparable for age, gender, dependency levels and cognition. After 6 months, the total number of medications per patient per day fell from 11.64 to 11.09 in the specialist group (P = 0.0364) and increased from 11.07 to 11.5 in the regular group (P = 0.094). There was no significant difference in mortality or frequency of acute hospital transfers (11 versus 6 in the specialist versus regular group, P = 0.213). CONCLUSION: specialist geriatric assessment and medication review in hospital continuing care resulted in a reduction in medication use, but at a significant cost. No benefits in hard clinical outcomes were demonstrated. However, qualitative benefits and lower costs may become evident over longer periods.

Cervical artery dissection following a turbulent flight.

BACKGROUND: Cervical artery dissection is a common cause of stroke in young patients without vascular risk factors and may affect the carotid or vertebral arteries. The risk of spontaneous dissection is higher in those with genetic predisposing factors while other cases may be precipitated by an event involving head or neck movement or associated with direct neck trauma. CASE REPORT: We present the case of a previously well young woman with a history of migraine who developed internal carotid artery dissection following a turbulent short-haul commercial flight while restrained using a seatbelt. DISCUSSION: We propose that repetitive flexion-hyperextension neck movements encountered during the flight were the most likely precipitant of carotid artery dissection in this case and review the therapeutic options available.

Delirium and abnormal autonomic nervous system response to head-up tilt testing.

BACKGROUND: Delirium is a common condition with poorly understood pathophysiology. Various theories have been proposed including that delirious patients have reduced cerebral blood flow. We hypothesised that patients with delirium could have abnormal autonomic nervous system function, as assessed by tilt table testing, which would explain the alteration in blood flow. METHODS: A prospective cohort study of medical inpatients aged 65 years and older was undertaken. Delirium was assessed using DRS-R98 and DSM-IV criteria. Beat-to-beat blood pressure (BP) was recorded during tilt testing. Differences in BP changes between the two groups (those with delirium and those without) were explored. The association between severity of delirium and magnitude of BP changes was also examined. RESULTS: 64 participants were recruited during hospitalisation. 29 completed follow-up Head-Up Tilt testing. The mean age of participants was 80.8 years (SD 6.2 years). The control group (n = 12) had a median decrease in systolic BP of 17.5 mmHg (IQR 20.75). The delirium group (n = 17) had a median decrease in systolic BP of 1 mmHg (IQR 38.5), p = 0.04. As delirium severity scores increased, systolic BP change during tilting also increased (rs = 0.42, p = 0.03). CONCLUSION: Participants in the delirium group showed different BP responses to tilt test which may represent abnormal sympathetic response. This would be consistent with other features of delirium such as treatment response to centrally acting alpha-2 blockers. Equity of access to research for older, frail and delirious cohorts is essential but feasibility and acceptability needs to be optimised and factored into study design.

Sleep Circuits and Physiology in Non-Mammalian Systems.

Research over the last 20 years has firmly established the existence of sleep states across the animal kingdom. Work in non-mammalian animal models such as nematodes, fruit flies, and zebrafish has now uncovered many evolutionarily conserved aspects of sleep physiology and regulation, including shared circuit architecture, homeostatic and circadian control elements, and principles linking sleep physiology to function. Non-mammalian sleep research is now shedding light on fundamental aspects of the genetic and neuronal circuit regulation of sleep, with direct implications for the understanding of how sleep is regulated in mammals.

A review of postural orthostatic tachycardia syndrome.

A 21-year-old female reports an 18-month history of light-headedness on standing. This is often associated with palpitations and a feeling of intense anxiety. She has had two black-outs in the past 12 months. She is not taking any regular medications. Her supine blood pressure was 126/84 mmHg with a heart rate of 76 bpm, and her upright blood pressure was 122/80 mmHg with a heart rate of 114 bpm. A full system examination was otherwise normal. She had a 12-lead electrocardiogram performed which was unremarkable. She was referred for head-up tilt testing. She was symptomatic during the test and lost consciousness at 16 min. Figure 1 summarizes her blood pressure and heart rate response to tilting. A diagnosis of postural orthostatic tachycardia syndrome with overlapping vasovagal syncope was made.

What is the optimal duration of tilt testing for the assessment of patients with suspected postural tachycardia syndrome?

AIMS: The aim of this study is to define the optimal duration of tilt testing for the assessment of patients with suspected postural tachycardia syndrome (POTS). METHODS AND RESULTS: This was a case-control study. Cases were identified retrospectively from a database of patients referred with orthostatic intolerance (OI). All met the diagnostic criteria for POTS. Controls were enrolled prospectively. All subjects underwent tilting to 70 degrees for 40 min if tolerated. Continuous monitoring was provided by a Finometer. Analysis of responses to tilting was performed on 28 cases and 28 controls. The mean age in the case group was 23.6 and in the control group was 26.2. The majority was female in both groups (cases = 4F:3M, controls = 2F:1M). All cases met the criteria for POTS within 7 min of orthostasis. No controls demonstrated a sustained tachycardia. The prevalence of vasovagal syncope (VVS) was 36% in cases vs. 7% in controls (P = 0.02) and 25% in the remaining patients (n = 233) on the OI database (P = 0.259). CONCLUSION: A 10 min tilt will diagnose POTS in the majority of patients. It will not, however, be sufficient to identify the overlap that exists between POTS and VVS. The optimal duration of tilt testing in patients suspected of POTS is 40 min.

Hip protectors in fracture prevention for aging adults at risk of falling: a study of user compliance.

PURPOSE: A compliance survey was conducted to establish factors that influence low user compliance with hip protectors amongst aging adults at risk of hip fracture. Medical professionals who deal with patients at risk of hip facture were also included in this survey. METHODS: For this descriptive study 2 questionnaires were designed, 1 for community dwelling aging adults at high risk of fall and hip fracture and 1 for medical professionals dealing with these patients. The questionnaires were presented, completed, and collected at individual appointments with aging adults and by group appointments with medical professionals. All data was statistically analysed to detect the most significant factors related to poor user compliance with hip protectors. For this descriptive study, frequency tests were used to analyse the data and therefore percentage of response was also reported. Certain demographic data such as age and gender was also collected. RESULTS: The outcomes in both interviewed groups were very similar. The main findings demonstrate that 51% of users find hip protectors very valuable while 41% reported the product to be uncomfortable and 29% of users found them difficult to put on. For potential users the high cost of the product and its appearance remains an issue. Also negative psychological aspects of wearing the hip orthoses appear to be common reasons for not wearing a hip protector. CONCLUSION: The study confirmed poor user compliance with hip protectors (18.9%). The information gathered from users and medical professionals regarding hip protectors provides valuable information which allows for the identification and development of new design features.

No relationship between fornix and cingulum degradation and within-network decreases in functional connectivity in prodromal Alzheimer's disease.

INTRODUCTION: The earliest changes in the brain due to Alzheimer's disease are associated with the neural networks related to memory function. We investigated changes in functional and structural connectivity among regions that support memory function in prodromal Alzheimer's disease, i.e., during the mild cognitive impairment (MCI) stage. METHODS: Twenty-three older healthy controls and 25 adults with MCI underwent multimodal MRI scanning. Limbic white matter tracts-the fornix, parahippocampal cingulum, retrosplenial cingulum, subgenual cingulum and uncinate fasciculus-were reconstructed in ExploreDTI using constrained spherical deconvolution-based tractography. Using a network-of-interest approach, resting-state functional connectivity time-series correlations among sub-parcellations of the default mode and limbic networks, the hippocampus and the thalamus were calculated in Conn. ANALYSIS: Controlling for age, education, and gender between group linear regressions of five diffusion-weighted measures and of resting state connectivity measures were performed per hemisphere. FDR-corrections were performed within each class of measures. Correlations of within-network Fisher Z-transformed correlation coefficients and the mean diffusivity per tract were performed. Whole-brain graph theory measures of cluster coefficient and average path length were inspecting using the resting state data. RESULTS & CONCLUSION: MCI-related changes in white matter structure were found in the fornix, left parahippocampal cingulum, left retrosplenial cingulum and left subgenual cingulum. Functional connectivity decreases were observed in the MCI group within the DMN-a sub-network, between the hippocampus and sub-areas -a and -c of the DMN, between DMN-c and DMN-a, and, in the right hemisphere only between DMN-c and both the thalamus and limbic-a. No relationships between white matter tract 'integrity' (mean diffusivity) and within sub-network functional connectivity were found. Graph theory revealed that changes in the MCI group was mostly restricted to diminished between-neighbour connections of the hippocampi and of nodes within DMN-a and DMN-b.

Enhancing acute stroke services: a quality improvement project.

BACKGROUND: In a busy stroke centre in Ireland, care for acute stroke was provided by a mixture of general physicians. In acute ischaemic stroke, speed is essential for good outcomes. AIM: To improve acute stroke services and decrease door-to-needle (DTN) time to less than 60 min by December 2016 in patients with acute ischaemic stroke who are eligible for intravenous thrombolysis.Design: A quality improvement (QI) project was undertaken in a 438 bed, acute, university hospital. METHODS: Mixture of qualitative and quantitative data collected. A process map and driver diagram were created. Interventions tested with Plan-Do-Study-Act cycles. Times compared between July and December 2015, January and July 2016, July and December 2016, when a new stroke team and pathway were introduced. RESULTS: Between July and December 2015, the total number of ischaemic strokes was 216. 17 were thrombolysed (7.8%). Median door-to-CT (DTCT) time was 36 min (range 21-88). Median DTN time was 99 min (range 52-239). Between July and December 2016, there were 214 ischaemic strokes. 29 were thrombolysed (13.5%). 9 were seen directly by the stroke team during normal hours. With stroke team involvement, median DTCT time was 34 min (range 14-60) and DTN time was 43.5 min (range 24-65). CONCLUSIONS: This project led to a significant and sustained improvement in acute stroke care in our hospital with the use of quality improvement techniques. A comprehensive protocol, recurrent and ongoing staff education, and good communication helped to mitigate delays and further enhance care provided to patients presenting with stroke. The approach described may be valuable to the improvement of other services.'

Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment.

Alzheimer's disease (AD) and its prodromal state amnestic mild cognitive impairment (aMCI) are characterized by widespread abnormalities in inter-areal white matter fiber pathways and parallel disruption of default mode network (DMN) resting state functional and effective connectivity. In healthy subjects, DMN and task positive network interaction are modulated by the thalamus suggesting that abnormal task-based DMN deactivation in aMCI may be a consequence of impaired thalamo-cortical white matter circuitry. Thus, this article uses a multimodal approach to assess white matter integrity between thalamus and DMN components and associated effective connectivity in healthy controls (HCs) relative to aMCI patients. Twenty-six HC and 20 older adults with aMCI underwent structural, functional and diffusion MRI scanning using the high angular resolution diffusion-weighted acquisition protocol. The DMN of each subject was identified using independent component analysis (ICA) and resting state effective connectivity was calculated between thalamus and DMN nodes. White matter integrity changes between thalamus and DMN were investigated with constrained spherical deconvolution (CSD) tractography. Significant structural deficits in thalamic white matter projection fibers to posterior DMN components posterior cingulate cortex (PCC) and lateral inferior parietal lobe (IPL) were identified together with significantly reduced effective connectivity from left thalamus to left IPL. Crucially, impaired thalamo-cortical white matter circuitry correlated with memory performance. Disrupted thalamo-cortical structure was accompanied by significant reductions in IPL and PCC cortico-cortical effective connectivity. No structural deficits were found between DMN nodes. Abnormal posterior DMN activity may be driven by changes in thalamic white matter connectivity; a view supported by the close anatomical and functional association of thalamic nuclei effected by AD pathology and the posterior DMN nodes. We conclude that dysfunctional posterior DMN activity in aMCI is consistent with disrupted cortico-thalamo-cortical processing and thalamic-based dissemination of hippocampal disease agents to cortical hubs.

Mapping oxygen concentration in the awake mouse brain.

Although critical for brain function, the physiological values of cerebral oxygen concentration have remained elusive because high-resolution measurements have only been performed during anesthesia, which affects two major parameters modulating tissue oxygenation: neuronal activity and blood flow. Using measurements of capillary erythrocyte-associated transients, fluctuations of oxygen partial pressure (Po2) associated with individual erythrocytes, to infer Po2 in the nearby neuropil, we report the first non-invasive micron-scale mapping of cerebral Po2 in awake, resting mice. Interstitial Po2 has similar values in the olfactory bulb glomerular layer and the somatosensory cortex, whereas there are large capillary hematocrit and erythrocyte flux differences. Awake tissue Po2 is about half that under isoflurane anesthesia, and within the cortex, vascular and interstitial Po2 values display layer-specific differences which dramatically contrast with those recorded under anesthesia. Our findings emphasize the importance of measuring energy parameters non-invasively in physiological conditions to precisely quantify and model brain metabolism.

Treatment of vasodepressor carotid sinus syndrome with midodrine: a randomized, controlled pilot study.

OBJECTIVES: To evaluate the efficacy of treatment of the vasodepressor form of carotid sinus hypersensitivity (carotid sinus syndrome (CSS)) with midodrine. DESIGN: A prospective, double-blind, randomized, controlled trial of crossover design. SETTING: A dedicated outpatient facility with access to tilt-table, digital arterial photoplethysmography, and 24-hour ambulatory blood pressure (BP) monitoring equipment. PARTICIPANTS: Ten older adults (4 male, 6 female, mean age 75, range 66-86 years) with a history of unexplained syncope who displayed an asymptomatic decrease in systolic BP (SBP) of more than 50 mmHg or a symptomatic decrease of more than 30 mmHg within 30 seconds of carotid sinus massage (CSM). MEASUREMENTS: Symptom reproduction and BP and heart rate changes were evaluated after CSM in supine and semierect positions on the right and then left sides. These measurements were performed on the final day of placebo and active-treatment phases. Ambulatory 24-hour BP monitoring took place on the penultimate and final days of each treatment phase. RESULTS: Eight patients were symptomatic after their initial CSM. The mean+/-standard deviation SBP decrease after initial CSM was 54+/-22 mmHg. Initial mean 24-hour ambulatory BP was 127/70+/-7/5 mmHg. Eight patients reported symptoms after CSM at the end of the placebo phase. The mean SBP decrease at the end of the placebo phase was 49+/-12 mmHg. The mean 24-hour ambulatory BP was 127/69+/-9/7 mmHg. One patient reported symptoms after CSM at the end of the active-treatment phase. The mean SBP decrease at the end of the active-treatment phase was 36+/-9 mmHg. The mean 24-hour ambulatory BP at the end of the treatment phase was 133/75+/-7/6 mmHg. The differences in symptom reporting and mean SBP decrease after CSM were both significant (P<.01 and P=.03, respectively). CONCLUSION: The results of this pilot study suggest that treatment of vasodepressor CSS with midodrine significantly reduced the rate of symptom reporting and attenuated SBP decreases after CSM but increased mean 24-hour ambulatory BP.