Real world prescribing practices of apixaban or rivaroxaban lead-in doses for the treatment of venous thromboembolism in hospitalized patients.

The oral factor Xa inhibitors (OFXAi) apixaban and rivaroxaban are increasingly utilized for the treatment of venous thromboembolism (VTE) with recommended initial higher dose 7- and 21-day lead-in regimens, respectively. In patients receiving initial parenteral anticoagulation, it remains unknown if the full recommended higher dose OFXAi lead-in regimens are warranted, or if days can be subtracted. We aimed to describe when clinicians may deviate from recommended lead-in durations and evaluate clinical outcomes in these scenarios. This is a retrospective, observational study of patients 18 years or older who were treated with rivaroxaban or apixaban for acute pulmonary embolism (PE) or symptomatic proximal deep vein thrombosis (DVT) that received parenteral anticoagulation for at least 24 h before transitioning to the OFXAi. Among our cohort of 171 patients with acute VTE who received parenteral anticoagulation for a median of 48 h, 134 (78%) were prescribed a full OFXAi lead-in and 37 (22%) were prescribed a reduced lead-in. Patients in the reduced lead-in group were older with more cardiac comorbidities and antiplatelet use. There were four recurrent thromboembolic events within 3 months, two in the reduced lead-in group and two in the full lead-in group (5% vs. 2%, p = 0.206). Bleeding within 3 months occurred in 9 (5%) patients, with 6 events occurring in the reduced lead-in group and 3 events in the full lead-in group (16% vs. 2%, p = 0.004). Prescribing patterns of OFXAi lead-in therapy duration are variable in patients receiving initial parenteral anticoagulation. Larger cohorts are needed to better define the safety and efficacy of lead-in reduction.

Surfeit folic acid, protein, and exercise modify oncogenic inflammatory biomarkers and fecal microbiota.

Intestinal microbiota, diet, and physical activity are inextricably linked to inflammation occurring in the presence of tumor progression and declining neurocognition. This study aimed to explore how fecal microbiota, inflammatory biomarkers, and neurocognitive behavior are influenced by voluntary exercise and surplus dietary protein and folic acid which are common health choices. Dietary treatments provided over 8 weeks to C57BL/CJ male mice (N = 76) were: Folic Acid (FA) Protein (P) Control (FPC, 17.9% P; 2 mgFA/kg); Folic Acid Deficient (FAD); Folic Acid Supplemented (FAS; 8 mgFA/kg); Low Protein Diet (LPD, 6% P); and High Protein Diet (HPD, 48% P). FAS mice had decreased plasma HCys (p < 0.05), therefore confirming consumption of FA. Objectives included examining influence of exercise using Voluntary Wheel Running (VWR) upon fecal microbiota, inflammatory biomarkers C - reactive protein (CRP), Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), nuclear factor kappa ß subunit (NF-κßp65), Caspase-3 (CASP3), Tumor Necrosis Factor-alpha (TNF-α), and neurocognitive behavior. CRP remained stable, while a significant exercise and dietary effect was notable with decreased VEGF (p < 0.05) and increased CASP3 (p < 0.05) for exercised HPD mice. Consumption of FAS did significantly increase (p < 0.05) muscle TNF-α and the ability to build a nest (p < 0.05) was significantly decreased for both FAD and LPD exercised mice. Rearing behavior was significantly increased (p < 0.05) in mice fed HPD. An emerging pattern with increased dietary protein intake revealed more distance explored in Open Field Testing. At week 1, both weighted and unweighted UniFrac principal coordinates analysis yielded significant clustering (permanova, p ≤ 0.05) associated with the specific diets. Consumption of a HPD diet resulted in the most distinct fecal microbiota composition. At the phylum level-comparing week 1 to week 8-we report a general increase in the Firmicutes/Bacteroidetes ratio, characterized by an outgrowth of Firmicutes by week 8 in all groups except the HPD. MaAsLin2 analysis corroborates this finding and emphasizes an apparent inversion of the microbiome composition at week 8 after HPD. Explicit modification of oncogenic inflammatory biomarkers and fecal microbiome post high FA and protein intake along with voluntary exercise contributed to current underlying evidence that this diet and exercise relationship has broader effects on human health and disease-perhaps importantly as a practical modulation of cancer progression and declining neurocognition.

Transient facial nerve palsy following dental local anaesthesia.

Facial nerve palsy is a rare but known complication of dental local anaesthesia and may be underreported. We describe a case of a transient facial nerve palsy following the administration of an inferior alveolar nerve block and discuss the immediate practical management. Knowing the likely transient nature of this complication means the patient can be reassured and unnecessary referral avoided. While the blink reflex is inhibited, steps are needed in order to protect the cornea and prevent secondary infection and scarring.

Effectiveness of nutritional countermeasures in microgravity and its ground-based analogues to ameliorate musculoskeletal and cardiopulmonary deconditioning-A Systematic Review.

A systematic review was performed to evaluate the effectiveness of nutrition as a standalone countermeasure to ameliorate the physiological adaptations of the musculoskeletal and cardiopulmonary systems associated with prolonged exposure to microgravity. A search strategy was developed to find all astronaut or human space flight bed rest simulation studies that compared individual nutritional countermeasures with non-intervention control groups. This systematic review followed the guidelines of the Cochrane Handbook for Systematic Reviews and tools created by the Aerospace Medicine Systematic Review Group for data extraction, quality assessment of studies and effect size. To ensure adequate reporting this systematic review followed the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses. A structured search was performed to screen for relevant articles. The initial search yielded 4031 studies of which 10 studies were eligible for final inclusion. Overall, the effect of nutritional countermeasure interventions on the investigated outcomes revealed that only one outcome was in favor of the intervention group, whereas six outcomes were in favor of the control group, and 43 outcomes showed no meaningful effect of nutritional countermeasure interventions at all. The main findings of this study were: (1) the heterogeneity of reported outcomes across studies, (2) the inconsistency of the methodology of the included studies (3) an absence of meaningful effects of standalone nutritional countermeasure interventions on musculoskeletal and cardiovascular outcomes, with a tendency towards detrimental effects on specific muscle outcomes associated with power in the lower extremities. This systematic review highlights the limited amount of studies investigating the effect of nutrition as a standalone countermeasure on operationally relevant outcome parameters. Therefore, based on the data available from the included studies in this systematic review, it cannot be expected that nutrition alone will be effective in maintaining musculoskeletal and cardiopulmonary integrity during space flight and bed rest.

A special role for the right posterior superior temporal sulcus during speech production.

This fMRI study of 24 healthy human participants investigated whether any part of the auditory cortex was more responsive to self-generated speech sounds compared to hearing another person speak. The results demonstrate a double dissociation in two different parts of the auditory cortex. In the right posterior superior temporal sulcus (RpSTS), activation was higher during speech production than listening to auditory stimuli, whereas in bilateral superior temporal gyri (STG), activation was higher for listening to auditory stimuli than during speech production. In the second part of the study, we investigated the function of the identified regions, by examining how activation changed across a range of listening and speech production tasks that systematically varied the demands on acoustic, semantic, phonological and orthographic processing. In RpSTS, activation during auditory conditions was higher in the absence of semantic cues, plausibly indicating increased attention to the spectral-temporal features of auditory inputs. In addition, RpSTS responded in the absence of any auditory inputs when participants were making one-back matching decisions on visually presented pseudowords. After analysing the influence of visual, phonological, semantic and orthographic processing, we propose that RpSTS (i) contributes to short term memory of speech sounds as well as (ii) spectral-temporal processing of auditory input and (iii) may play a role in integrating auditory expectations with auditory input. In contrast, activation in bilateral STG was sensitive to acoustic input and did not respond in the absence of auditory input. The special role of RpSTS during speech production therefore merits further investigation if we are to fully understand the neural mechanisms supporting speech production during speech acquisition, adult life, hearing loss and after brain injury.

A retrospective analysis of the periprocedural management of oral anticoagulants in patients undergoing interventional radiology procedures.

Limited evidence is available to guide periprocedural management of oral anticoagulants in the setting of interventional radiology (IR) procedures. For direct oral anticoagulants, therapy interruption (TI) is based on medication half-life and procedural bleeding risk. Periprocedural management of warfarin includes INR monitoring, and possible bridging with parenteral anticoagulants. It is unknown if these recommendations apply to IR procedures. To evaluate bleeding complications and thromboembolic events following periprocedural management of the factor Xa (FXa) inhibitors or warfarin in patients undergoing IR procedures. We performed a retrospective, observational study at NYU Langone Health (NYULH) of all adult patients who underwent an IR procedure from January 2015 to July 2017 and were receiving apixaban, rivaroxaban, or warfarin. Patients who were pregnant or who had a mechanical heart valve were excluded. At NYULH, TI is not required for FXa inhibitors, and an INR < 3 is recommended for patients on warfarin undergoing low risk procedures. For moderate/high risk procedures, TI for 48 h or 72 h with reduced renal function, is recommended for FXa inhibitors, and an INR < 1.5 is recommended for patients on warfarin. We evaluated 350 IR procedures, with a total of 174 low bleeding risk and 176 moderate/high bleeding risk. The 30-day major bleeding rate was 0.9%, clinically relevant non-major bleeding rate was 3%, minor bleeding rate was 1% and thromboembolic event rate was 1%. The periprocedural oral anticoagulation management strategy at NYULH appears safe given the low 30-day incidence of bleeding and thromboembolic events.

Vaccination in pregnancy: Attitudes of nurses, midwives and health visitors in England.

OBJECTIVE: To examine amongst healthcare professionals in England; knowledge of vaccinations in pregnancy, their perceived roles in these programmes and whether they recommend scheduled vaccines to pregnant women. DESIGN: Cross sectional survey (online questionnaire) Setting: Healthcare workers in contact with pregnant women in England. PARTICIPANTS: The survey analysis included 3441 healthcare workers who had been surveyed during May to August 2015. The participants were midwives, practice nurses and health visitors, working in England who were members of the Royal College of Midwives, Royal College of Nursing and the Institute of Health Visiting. RESULTS: We found that knowledge of vaccination in pregnancy was high in all professional groups. Seventy three percent of all respondents would recommend the influenza vaccine and 74% would recommend the pertussis vaccine to pregnant women. They were more likely to recommend vaccination in pregnancy if they would personally have the influenza and pertussis vaccines themselves and/or if they had the influenza vaccine as a healthcare worker. Practice nurses were significantly more likely to recommend the pertussis and influenza vaccines to pregnant women than midwives and health visitors. Health professionals who had received immunisation training were more confident in giving advice to pregnant women. CONCLUSION: Immunisation training is essential if healthcare workers are to be informed and confident in effectively delivering the maternal immunisation programme and thus improving uptake of vaccines in pregnancy. These findings are important in tailoring educational programmes and addressing the training needs of different healthcare professional groups.

Anticoagulation prescribing patterns in patients with cancer.

Cancer is a known hypercoagulable state that leads to an increased risk of venous thromboembolism (VTE). Low molecular weight heparin remains the preferred anticoagulant for VTE in patients with cancer over vitamin K antagonist. However, the preferred anticoagulant in prevention of stroke and systemic embolism in atrial fibrillation (AF) in patients with cancer has yet to be determined. The direct oral anticoagulants (DOACs) are increasingly being utilized; however their role in cancer has only recently been investigated. The objective of this retrospective cohort was to describe real-world anticoagulation prescribing patterns in cancer patients at a large academic medical center between January 1, 2013 and October 31, 2016. We sought to assess the safety, tolerability, and efficacy of DOACs in patients with cancer for either VTE and/or AF. Patient demographic, clinical characteristics, as well as bleeding and thrombotic events were collected. There were 214 patients in our analysis, of which 71 patients (33%) received a DOAC [apixaban (n = 22), dabigatran (n = 17), and rivaroxaban (n = 32)]. There were fewer bleeding events and/or discontinuations in the DOAC group compared to enoxaparin (13 vs. 27, p = 0.022). There was no difference in major or minor bleeds or thromboembolic events in comparing DOAC to enoxaparin or DOAC to warfarin. This was a retrospective, single-institution study assessing the safety and efficacy of DOACs compared to warfarin or enoxaparin in patients with cancer. DOACs may represent an alternative to warfarin or enoxaparin in patients with cancer for VTE and/or stroke reduction in AF.

L-type calcium channels refine the neural population code of sound level.

The coding of sound level by ensembles of neurons improves the accuracy with which listeners identify how loud a sound is. In the auditory system, the rate at which neurons fire in response to changes in sound level is shaped by local networks. Voltage-gated conductances alter local output by regulating neuronal firing, but their role in modulating responses to sound level is unclear. We tested the effects of L-type calcium channels (CaL: CaV1.1-1.4) on sound-level coding in the central nucleus of the inferior colliculus (ICC) in the auditory midbrain. We characterized the contribution of CaL to the total calcium current in brain slices and then examined its effects on rate-level functions (RLFs) in vivo using single-unit recordings in awake mice. CaL is a high-threshold current and comprises ∼50% of the total calcium current in ICC neurons. In vivo, CaL activates at sound levels that evoke high firing rates. In RLFs that increase monotonically with sound level, CaL boosts spike rates at high sound levels and increases the maximum firing rate achieved. In different populations of RLFs that change nonmonotonically with sound level, CaL either suppresses or enhances firing at sound levels that evoke maximum firing. CaL multiplies the gain of monotonic RLFs with dynamic range and divides the gain of nonmonotonic RLFs with the width of the RLF. These results suggest that a single broad class of calcium channels activates enhancing and suppressing local circuits to regulate the sensitivity of neuronal populations to sound level.

Inspiratory high frequency airway oscillation attenuates resistive loaded dyspnea and modulates respiratory function in young healthy individuals.

Direct chest-wall percussion can reduce breathlessness in Chronic Obstructive Pulmonary Disease and respiratory function may be improved, in health and disease, by respiratory muscle training (RMT). We tested whether high-frequency airway oscillation (HFAO), a novel form of airflow oscillation generation can modulate induced dyspnoea and respiratory strength and/or patterns following 5 weeks of HFAO training (n = 20) compared to a SHAM-RMT (conventional flow-resistive RMT) device (n = 15) in healthy volunteers (13 males; aged 20-36 yrs). HFAO causes oscillations with peak-to-peak amplitude of 1 cm H2O, whereas the SHAM-RMT device was identical but created no pressure oscillation. Respiratory function, dyspnoea and ventilation during 3 minutes of spontaneous resting ventilation, 1 minute of maximal voluntary hyperventilation and 1 minute breathing against a moderate inspiratory resistance, were compared PRE and POST 5-weeks of training (2 × 30 breaths at 70% peak flow, 5 days a week). Training significantly reduced NRS dyspnoea scores during resistive loaded ventilation, both in the HFAO (p = 0.003) and SHAM-RMT (p = 0.005) groups. Maximum inspiratory static pressure (cm H2O) was significantly increased by HFAO training (vs. PRE; p<0.001). Maximum inspiratory dynamic pressure was increased by training in both the HFAO (vs. PRE; p<0.001) and SHAM-RMT (vs. PRE; p = 0.021) groups. Peak inspiratory flow rate (L.s(-1)) achieved during the maximum inspiratory dynamic pressure manoeuvre increased significantly POST (vs. PRE; p = 0.001) in the HFAO group only. HFAO reduced inspiratory resistive loading-induced dyspnoea and augments static and dynamic maximal respiratory manoeuvre performance in excess of flow-resistive IMT (SHAM-RMT) in healthy individuals without the respiratory discomfort associated with RMT.

Lipiodol embolism following transarterial chemoembolization: an atypical case.

OBJECTIVE: Transarterial chemoembolization is a widely used therapy for the treatment of hepatocellular carcinoma. A rare adverse event is acute respiratory distress syndrome from pulmonary embolization of Lipiodol, an iodinated oil commonly used during the procedure. The objective of this report is to describe an atypical case of acute respiratory distress syndrome from Lipiodol embolization in a patient who underwent transarterial chemoembolization for hepatocellular carcinoma 9 days prior to presentation, despite having received relatively small amounts of Lipiodol (5.5 mL). Although this diagnosis has classically been based on radiological findings, we established a diagnosis after lipid-laden macrophages were detected in bronchial alveolar lavage fluid. DESIGN: Case report. SETTING: ICU of a major metropolitan academic medical center. PATIENTS: Single case. INTERVENTIONS: Diagnostic interventions included noncontrast CT scan of the chest and cytologic examination of bronchial alveolar lavage fluid with oil red O staining. Therapeutic interventions included mechanical ventilation and methylprednisolone infusions. MEASUREMENTS AND MAIN RESULTS: Noncontrast CT demonstrated nonspecific diffuse ground glass opacification, most prominent within the upper lobes. Mechanical ventilation was begun for hypoxemic respiratory failure. Cytologic examination of bronchial alveolar lavage fluid revealed a high proportion of lipid-laden macrophages, findings consistent with Lipiodol embolism. Despite infusions of methylprednisolone, the patient expired on hospital day 8. CONCLUSIONS: Acute respiratory distress syndrome from Lipiodol embolization following transarterial chemoembolization can occur even with small Lipiodol volumes. Cytologic examination of bronchial alveolar lavage fluid with oil red O staining is a useful diagnostic modality, especially when imaging studies are equivocal.

Postural prioritization is differentially altered in healthy older compared to younger adults during visual and auditory coded spatial multitasking.

Many daily activities require appropriate allocation of attention between postural and cognitive tasks (i.e. dual-tasking) to be carried out effectively. Processing multiple streams of spatial information is important for everyday tasks such as road crossing. Fifteen community-dwelling healthy older (mean age=78.3, male=1) and twenty younger adults (mean age=25.3, male=6) completed a novel bimodal spatial multi-task test providing contextually similar spatial information via separate sensory modalities to investigate effects on postural prioritization. Two tasks, a temporally random visually coded spatial step navigation task (VS) and a regular auditory-coded spatial congruency task (AS) were performed independently (single task) and in combination (multi-task). Response time, accuracy and dual-task costs (% change in multi-task condition) were determined. Results showed a significant 3-way interaction between task type (VS vs. AS), complexity (single vs. multi) and age group for both response time (p ≤ 0.01) and response accuracy (p ≤ 0.05) with older adults performing significantly worse than younger adults. Dual-task costs were significantly greater for older compared to younger adults in the VS step task for both response time (p ≤ 0.01) and accuracy (p ≤ 0.05) indicating prioritization of the AS over the VS stepping task in older adults. Younger adults display greater AS task response time dual task costs compared to older adults (p ≤ 0.05) indicating VS task prioritization in agreement with the posture first strategy. Findings suggest that novel dual modality spatial testing may lead to adoption of postural strategies that deviate from posture first, particularly in older people. Adoption of previously unreported postural prioritization strategies may influence balance control in older people.

Public perceptions of the risks, benefits and use of natural remedies, pharmaceutical medicines and personalised medicines.

OBJECTIVE: To investigate public perceptions of the benefits, risks and use of a natural remedy, a pharmaceutical medicine and a personalised medicine, tailored to a person's genetic-makeup, to treat illness. DESIGN AND OUTCOME MEASURES: In a case-based scenario, groups of participants individually rated the three different treatments of an illness in terms of their perceived benefits, risks and willingness to use, and completed a questionnaire on beliefs about medicines in general. RESULTS: Our study (n=158 adults) revealed a similar perception of a pharmaceutical medicine and a personalised medicine relative to a natural remedy. Contrary to expectation, personalised medicine was rated as no more beneficial and no less risky than a pharmaceutical medicine and was less likely to be used. However, willingness to use each medicine was differentially predicted by general beliefs about medicine. Avoidance of harm predicted willingness to use a natural remedy whereas the beneficial effects of medicines predicted use of a personalised medicine. By contrast, willingness to use a pharmaceutical medicine was predicted by a trade-off between perceived harm, risk of overuse and benefit. CONCLUSION: Personalised medicine, in the form of a pharmacogenetic approach, has the potential to improve drug efficacy and reduce adverse drug reactions but remains closely allied to public perceptions of pharmaceutical medicine. Nonetheless our data indicate some differentiation with respect to background beliefs on the beneficial effects of personalised medicine.

Preventive effect of specific antioxidant on oxidative renal cell injury associated with renal crystal formation.

OBJECTIVE: To investigate whether calcium oxalate monohydrate (COM), a key element of hyperoxaluria, would induce renal cell injury through oxidative stress and also whether certain antioxidants could prevent chemically induced renal crystal formation in rats. MATERIALS AND METHODS: COM-exerted oxidative stress on the kidney epithelial Madin-Darby canine kidney cells was assessed using the lipid peroxidation assay. Glyoxalase I (Gly-I) activity was also determined. Two antioxidants, vitamin C and N-acetylcysteine (NAC), were then tested to determine whether they could abolish such oxidative stress in Madin-Darby canine kidney cells. Both antioxidants were also tested to determine whether they might prevent or reduce renal crystal formation induced with ethylene glycol (EG) and vitamin D3 (VD3) in Wistar rats. RESULTS: COM (200 µg/mL) demonstrated ∼1.3-fold greater oxidative stress with a significant reduction in cell viability and Gly-I activity compared with controls. However, such adverse events were almost completely prevented with NAC but not with vitamin C. In the animal study, no renal crystals were seen in the sham group. However, numerous crystals, with reduced Gly-I activity and elevated oxidative stress, were found in the EG-VD3 group. However, markedly (>70%) fewer crystals, with full Gly-I activity and diminished oxidative stress, were detected in the EG-VD3+NAC group. CONCLUSION: COM exerted oxidative stress on Madin-Darby canine kidney cells, leading to cell viability reduction and Gly-I inactivation, with NAC fully preventing such adverse consequences. Similarly, numerous crystals with Gly-I inactivation and elevated oxidative stress seen in the rats (EG-VD3) were also significantly prevented with NAC supplement. Thus, NAC might have clinical implications in preventing oxidative renal cell injury and, ultimately, kidney stone formation.

The right posterior paravermis and the control of language interference.

Auditory and written language in humans' comprehension necessitates attention to the message of interest and suppression of interference from distracting sources. Investigating the brain areas associated with the control of interference is challenging because it is inevitable that activation of the brain regions that control interference co-occurs with activation related to interference per se. To isolate the mechanisms that control verbal interference, we used a combination of structural and functional imaging techniques in Italian and German participants who spoke English as a second language. First, we searched structural MRI images of Italian participants for brain regions in which brain structure correlated with the ability to suppress interference from the unattended dominant language (Italian) while processing heard sentences in their weaker language (English). This revealed an area in the posterior paravermis of the right cerebellum in which gray matter density was higher in individuals who were better at controlling verbal interference. Second, we found functional activation in the same region when our German participants made semantic decisions on written English words in the presence of interference from unrelated words in their dominant language (German). This combination of structural and functional imaging therefore highlights the contribution of the right posterior paravermis to the control of verbal interference. We suggest that the importance of this region for language processing has previously been missed because most fMRI studies limit the field of view to increase sensitivity, with the lower part of the cerebellum being the region most likely to be excluded.

Cerebral monitoring in patients undergoing carotid endarterectomy using a triple assessment technique.

OBJECTIVES: Selective shunting during carotid endarterectomy (CEA) is advocated to reduce shunt related stroke. Cerebral monitoring is essential for temporary carotid shunting. Many techniques are available for cerebral monitoring, however, none is superior to monitoring the patient's neurological status (awake testing) while performing the procedure under local anaesthesia (LA). Cerebral oximetry (CO) and trans-cranial Doppler (TCD) has previously been used to show the adequacy of cerebral circulation in patients undergoing CEA. The aim of this study is to assess the reliability of CO and TCD in predicting the need for shunting compared to the awake testing. METHODS: Patients scheduled for CEA under LA were included. Patients converted to general anaesthesia (GA) and patients with no TCD window were excluded from the study. The Somanetics INVOS(®) CO was used for ipsilateral cerebral monitoring in all patients, in addition to TCD and awake testing. The percentage fall in CO regional oxygen saturation (rSO(2)), and decline in the mean flow velocity (FVm) in TCD following carotid artery clamping recorded. A drop in rSO(2) of ≥20% or FVm of ≥50% was considered an indicator of cerebral ischaemia that may predict the need for carotid shunting. Patients only shunted based on awake testing. RESULTS: Forty-nine patients underwent triple assessment. The median clamp time was 24 min. 8/49 patients (16.3%) needed carotid shunting based on awake testing. In this group, six patients had ≥20% drop in rSO(2), and ≥50% drop in FVm. However, two patients had a non-significant drop in both rSO(2) and FVm (false negative). In the non-shunted group (41/49), one patient had a significant drop in rSO(2) (false positive) while 10/41 patients had a >50% drop in FVm. This represents sensitivity of 75%, and specificity of 97.5% for CO compared to sensitivity of 75% and specificity of 75% for TCD in prediction of shunting. The positive predictive value and negative predictive value were 85.7 and 95.2%, respectively for CO, compared to 37.5 and 93.9% for TCD. CONCLUSIONS: TCD is less accurate than CO in predicting the need for carotid shunting during CEA. A combination of both methods does not add to the accuracy of detecting the need for carotid shunting.

Glycosylated tetrahydrosalens as multifunctional molecules for Alzheimer's therapy.

The tetrahydrosalens N,N'-bis(2-hydroxybenzyl)-ethane-1,2-diamine ((2)(1)), N,N'-bis(2-hydroxybenzyl)-(-)-1,2-cyclohexane-(1R,2R)-diamine ((2)(2)), N,N'-bis(2-hydroxybenzyl)-N,N'-dimethyl-ethane-1,2-diamine ((2)(3)), N,N'-bis(2-hydroxybenzyl)-N,N'-dibenzyl-ethane-1,2-diamine ((2)(4)), and N,N'-bis(2-(4-tert-butyl)hydroxybenzyl)-ethane-1,2-diamine ((2)(5)), as well as their prodrug glycosylated forms, (1-5), have been prepared and evaluated in vitro for their potential use as Alzheimer's disease (AD) therapeutics. Dysfunctional interactions of metal ions, especially those of Cu, Zn, and Fe, with the amyloid-beta (Abeta) peptide are hypothesised to play an important role in the aetiology of AD, and disruption of these aberrant metal-peptide interactions via chelation therapy holds considerable promise as a therapeutic strategy. Tetrahydrosalens such as (2)(1-5) have a significant affinity for metal ions, and thus should be able to compete with the Abeta peptide for Cu, Zn, and Fe in the brain. This activity was assayed in vitrovia a turbidity assay; (2)(1) and (2)(3) were found to attenuate Abeta(1-40) aggregation after exposure to Cu(2+) and Zn(2+). In addition, (2)(1-5) were determined to be potent antioxidants on the basis of an in vitro antioxidant assay. (1-5) were prepared as metal binding prodrugs; glycosylation is intended to prevent systemic metal binding, improve solubility, and enhance brain uptake. Enzymatic (beta-glucosidase) deprotection of the carbohydrate moieties was facile, with the exception of (4), demonstrating the general feasibility of this prodrug approach. Finally, a representative prodrug, (3), was determined to be non-toxic over a large concentration range in a cell viability assay.

Electrical percutaneous tibial stimulation modulates within-a-breath respiratory drive in man.

A sharp intake of breath followed by a strong vocalisation is widely observed in response to acute pain although its function and mechanism is poorly understood. This study investigated the effect of percutaneous (overlying the tibial bone) electrical stimulation delivered early (20-30% of inspiratory time) during inspiration (INSP) or expiration (EXP) (20-30% of expiratory time) at sensory intensities at (100%), above (125%) and below (50% and 75%) the pre-determined pain threshold (PT), upon within-a-breath respiratory parameters (via pneumotachography). All INSP stimulation intensities provoked significant inspiratory time shortening thereby elevating mean inspiratory flow. Tidal volume, but not peak flow was increased in response to 100% PT and 125% PT stimulation (vs. PRE). Shortening and increased tidal volume combined to evoke significant mean inspiratory airflow increments. In contrast, EXP stimulation failed to evoke any effect. Thus, our study provides evidence of a within-a-breath inspiratory-specific, augmentory response to noxious stimulation.