A qualitative evaluation of internet information on hip and knee osteoarthritis.

BACKGROUND: Hip and knee arthritis are two of the most common conditions that result in referral to orthopaedic outpatient clinics. Many patients now use the internet to research their condition and to inform their decision about treatment options. This has implications for the process of informed consent. AIM: To assess the quality of patient information on the internet regarding hip and knee arthritis. METHODS: 'Hip arthritis' and 'Knee arthritis' were entered as search terms into a popular search engine. To adjust for temporal variation, the process was repeated one month and one year later. Of the 200 results analysed, 83 websites met the inclusion criteria. The quality of patient information presented on these websites was assessed using a validated scoring instrument by two independent observers. RESULTS: Most websites assessed were of poor quality; nearly half of all websites did not mention any risks or complications associated with surgical intervention for these conditions. CONCLUSIONS: As part of their professional obligation to provide a robust process of informed consent, clinicians should be aware of the variable quality of patient information available on the internet. As such, they should be prepared to advise their patients about quality websites where reliable information can be sought.

Long-term impact of early non-infectious complications at the initiation of peritoneal dialysis.

BACKGROUND: Early non-infectious complications at initiation of peritoneal dialysis (PD) are a major burden with unknown long-term impacts on individuals. METHODS: Prospective multicentre cohort study using univariable and multivariable Cox regression to identity mortality risk and PD discontinuation risk in those with and without non-infectious complications. All individuals commencing PD between 1 January 2014 and 31 December 2018, registered in the New Zealand Peritoneal Dialysis Registry (NZPDR) were followed up to 31 December 2020. Early non-infectious complications defined as functional, catheter-related, exit-site dialysate leak or anatomical leak complications occurring within 30 days of initiation of PD. Primary outcomes were patient survival and time on PD therapy. Secondary outcomes were peritonitis free survival, first PD catheter survival and catheter tunnel infection free survival. RESULTS: Of 1596 individuals included in the study, 102 experienced an early non-infectious complication. Multivariable analysis demonstrated these complications were associated with higher risk of overall mortality (hazard ratio (HR) 1.71; 95% confidence interval (CI) 1.21-2.44), PD discontinuation (HR 1.84; 95% CI 1.41-2.41) and first catheter failure (HR 2.89; 95% CI 2.28-3.66). No difference was found for risk of development of first peritonitis episode or catheter tunnel infection. Mortality risk was associated with functional and exit-site dialysate leak complications and continued beyond 180 days. Risk of PD discontinuation and first catheter loss were associated with catheter and functional complications in the first 180 days. CONCLUSION: Early non-infectious complications are associated with long-term mortality risk. Further research in risk factors and causes of early non-infectious complications are required.

The effect of spironolactone on cardiac and renal fibrosis following myocardial infarction in established hypertension in the transgenic Cyp1a1Ren2 rat.

AIMS: The renin-angiotensin-aldosterone axis plays a key role in mediating cardiac and kidney injury. Mineralocorticoid receptor antagonism has beneficial effects on cardiac dysfunction, but effects are less well quantified in the cardiorenal syndrome. This study investigated cardiac and kidney pathophysiology following permanent surgical ligation to induce myocardial infarction (MI) in hypertensive animals with or without mineralocorticoid receptor antagonism. METHODS: Hypertension was induced in adult male Cyp1a1Ren2 rats. Hypertensive animals underwent MI surgery (n = 6), and were then treated daily with spironolactone for 28 days with serial systolic blood pressure measurements, echocardiograms and collection of urine and serum biochemical data. They were compared to hypertensive animals (n = 4), hypertensive animals treated with spironolactone (n = 4), and hypertensive plus MI without spironolactone (n = 6). Cardiac and kidney tissue was examined for histological and immunohistochemical analysis. RESULTS: MI superimposed on hypertension resulted in an increase in interstitial cardiac fibrosis (p<0.001), renal cortical interstitial fibrosis (p<0.01) and glomerulosclerosis (p<0.01). Increased fibrosis was accompanied by myofibroblast and macrophage infiltration in the heart and the kidney. Spironolactone post-MI, diminished the progressive fibrosis (p<0.001) and inflammation (myofibroblasts (p<0.05); macrophages (p<0.01)) in both the heart and the kidney, despite persistently elevated SBP (182±19 mmHg). Despite the reduction in inflammation and fibrosis, spironolactone did not modify ejection fraction, proteinuria, or renal function when compared to untreated animals post MI. CONCLUSION: This model of progressive cardiorenal dysfunction more closely replicates the clinical setting. Mineralocorticoid receptor blockade at a clinically relevant dose, blunted progression of cardiac and kidney fibrosis with reduction in cardiac and kidney inflammatory myofibroblast and macrophage infiltration. Further studies are underway to investigate the combined actions of angiotensin blockade with mineralocorticoid receptor blockade.

Indomethacin markedly blunts cerebral perfusion and reactivity, with little cognitive consequence in healthy young and older adults.

KEY POINTS: Cognitive function depends on adequate cerebrovascular perfusion and control. However, it is unknown whether acutely-reduced cerebral blood flow (CBF) impairs cognition in healthy adults. In the present study, we used a placebo-controlled, single-blinded, randomized cross-over design to test the hypothesis that acutely-reduced CBF (using a pharmacological aid; indomethacin) would impair cognition in young and older healthy adults. At baseline, older adults had lower cognitive performance and CBF, but similar cerebrovascular reactivity to CO2 and dynamic cerebral autoregulation compared to young adults. In both young and older adults, cognitive performance on a mental switching task was slightly (7%) reduced after indomethacin, but not significantly associated with reductions in CBF (∼31%). These results indicate that cognitive performance is broadly resilient against a ∼31% reduction in CBF per se in healthy young and older adults. ABSTRACT: Cognitive function depends on adequate cerebrovascular perfusion and control. However, it is unknown whether acutely-reduced cerebral blood flow (CBF) impairs cognition in healthy adults. Using a placebo-controlled, single-blinded, randomized cross-over design, we tested the hypothesis that acutely-reduced CBF (using indomethacin [1.2 mg kg-1 oral dose]) would impair cognition in young (n = 13; 25 ± 4 years) and older (n = 12; 58 ± 6 years) healthy adults. CBF and cerebrovascular control were measured using middle cerebral artery blood velocity (MCAvmean ) and its reactivity to hypercapnia (CVRHYPER ) and hypocapnia (CVRHYPO ), respectively. Cognitive function was assessed using a computerized battery including response time tasks. Baseline comparisons revealed that older adults had 14% lower MCAvmean and 15% lower cognitive performance (all P ≤ 0.048), but not lower CVRHYPER/HYPO (P ≥ 0.26). Linear and rank-based mixed models revealed that indomethacin decreased MCAvmean by 31% (95% confidence interval = -35 to -26), CVRHYPER by 68% [interquartile range (IQR) = -94 to -44] and CVRHYPO by 50% (IQR = -83 to -33) (treatment-effect; all P < 0.01), regardless of age. Baseline CVRHYPER/HYPO values were strongly associated with their indomethacin-induced reductions (r = 0.70 to 0.89, P < 0.01). Mental switching performance was impaired 7% (IQR = 0-19) after indomethacin (P = 0.04), but not significantly associated with reductions in MCAvmean (Young: rho = -0.31, P = 0.30; Older: rho = 0.06, P = 0.86). In conclusion, indomethacin reduced MCAvmean and impaired cognition slightly; however, no clear association was evident in younger or older adults. Older adults had poorer cognition and lower MCAvmean , but similar CVRHYPER/HYPO .

Relationship between adverse childhood experiences and perceived discrimination in adulthood.

BACKGROUND: Adverse Childhood Experiences (ACEs) and perceived discrimination impact health overtime, however little is known about their association. METHODS: Data for 6,325 participants in the Midlife in the US (MIDUS) study were analyzed across three waves of data. ACEs included emotional or physical abuse, household dysfunction, or financial strain in childhood. Generalized Linear Models with Generalized Estimating Equation approach was used to test the unadjusted and adjusted associations for ACEs and perceived discrimination and perceived inequality. RESULTS: Individuals with ACEs reported significantly higher perceived inequality in work (ß=0.05, 95%CI 0.02-0.07), in home (ß=0.06, 95%CI 0.04-0.09), in family relationships (ß=0.09, 95%CI 0.06-0.11), perceived daily discrimination (ß=0.77, 95%CI 0.58-0.96), and perceived lifetime discrimination (ß=0.24, 95%CI 0.18-0.30). ACE types were significantly associated with more perceived inequality and perceived discrimination. . Abuse was independently associated with all outcomes after adjusting for household dysfunction, financial strain, age, sex, race/ethnicity, education, marital status, and income. LIMITATIONS: Findings cannot speak to the temporal relationship between ACEs and discrimination. It should not be assumed that ACEs cause perceived discrimination, but rather that there is an important association that warrants further investigation. CONCLUSIONS: These findings represent the first step in better understanding the relationship between ACEs and perceived discrimination. As both influence health across the lifespan, understanding the relationship, mechanisms, and pathways for intervening are of great importance from a population health perspective. Efforts to incorporate discussions on experiences with discrimination and inequality may be warranted as a part of treatment for ACEs to address psychosocial stressors across the lifespan.

Podocyte GSK3 is an evolutionarily conserved critical regulator of kidney function.

Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity and death. The key cell that prevents albuminuria is the terminally differentiated glomerular podocyte. Here we report the evolutionary importance of the enzyme Glycogen Synthase Kinase 3 (GSK3) for maintaining podocyte function in mice and the equivalent nephrocyte cell in Drosophila. Developmental deletion of both GSK3 isoforms (α and ß) in murine podocytes causes late neonatal death associated with massive albuminuria and renal failure. Similarly, silencing GSK3 in nephrocytes is developmentally lethal for this cell. Mature genetic or pharmacological podocyte/nephrocyte GSK3 inhibition is also detrimental; producing albuminuric kidney disease in mice and nephrocyte depletion in Drosophila. Mechanistically, GSK3 loss causes differentiated podocytes to re-enter the cell cycle and undergo mitotic catastrophe, modulated via the Hippo pathway but independent of Wnt-ß-catenin. This work clearly identifies GSK3 as a critical regulator of podocyte and hence kidney function.

Investigation of feeding behaviour in C. elegans reveals distinct pharmacological and antibacterial effects of nicotine.

Caenorhabditis elegans is an informative model to study the neural basis of feeding. A useful paradigm is one in which adult nematodes feed on a bacterial lawn which has been pre-loaded with pharmacological agents and the effect on pharyngeal pumping rate scored. A crucial aspect of this assay is the availability of good quality bacteria to stimulate pumping to maximal levels. A potential confound is the possibility that the pharmacological agent impacts bacterial viability and indirectly influences feeding rate. Here, the actions of nicotine on pharyngeal pumping of C. elegans and on the Escherichia coli bacterial food source were investigated. Nicotine caused an immediate and concentration-dependent inhibition of C. elegans pharyngeal pumping, IC50 4 mM (95% CI = 3.4 mM to 4.8 mM). At concentrations between 5 and 25 mM, nicotine also affected the growth and viability of E. coli lawns. To test whether this food depletion by nicotine caused the reduced pumping, we modified the experimental paradigm. We investigated pharyngeal pumping stimulated by 10 mM 5-HT, a food 'mimic', before testing if nicotine still inhibited this behaviour. The IC50 for nicotine in these assays was 2.9 mM (95% CI = 3.1 mM to 5.1 mM) indicating the depletion of food lawn does not underpin the potency of nicotine at inhibiting feeding. These studies show that the inhibitory effect of nicotine on C. elegans pharyngeal pumping is mediated by a direct effect rather than by its poorly reported bactericidal actions.

The differential impact of adverse childhood experiences in the development of pre-diabetes in a longitudinal cohort of US adults.

BACKGROUND: ACEs have a dose-response relationship with diabetes. The relationship between ACEs and pre-diabetes is not well known and may represent an effective area for prevention efforts. METHODS: Data from 1054 participants from two waves of the longitudinal MIDUS study were used. Multivariate general linear regression models assessed the relationship between ACEs and biomarker outcomes. Correlation tests and mediation models investigated the relationship between ACE and pre-diabetes. RESULTS: Individuals reporting ACEs were statistically significantly more likely to have higher BMI (1.13 (0.34-1.92)), higher waist circumference (2.74 (0.72-4.76)), elevated blood fasting insulin levels (2.36 (0.71-4.02)) and higher insulin resistance (HOMA-IR (0.57 (0.08-1.06)). BMI/waist circumference and insulin resistance did not maintain independent relationships with ACEs once HOMA-IR was included in the dichotomized ACE model (p = 0.05 and p = 0.06, respectively), suggesting the relationship between BMI and ACEs may be mediated by insulin resistance. CONCLUSIONS: These results represent one of the first studies to examine the differential impact of ACEs on a diverse set of clinical pre-diabetes measures. Findings suggest sexual and physical abuse, and financial strain during childhood are important factors associated with higher risk for pre-diabetes, and should be considered during intervention development.

New insights into Mo and Ru isotope variation in the nebula and terrestrial planet accretionary genetics.

When corrected for the effects of cosmic ray exposure, Mo and Ru nucleosynthetic isotope anomalies in iron meteorites from at least nine different parent bodies are strongly correlated in a manner consistent with variable depletion in s-process nucleosynthetic components. In contrast to prior studies, the new results show no significant deviations from a single correlation trend. In the refined Mo-Ru cosmic correlation, a distinction between the non-carbonaceous (NC) group and carbonaceous chondrite (CC) group is evident. Members of the NC group are characterized by isotope compositions reflective of variable s-process depletion. Members of the CC group analyzed here plot in a tight cluster and have the most s-process depleted Mo and Ru isotopic compositions, with Mo isotopes also slightly enriched in r- and possibly p-process contributions. This indicates that the nebular feeding zone of the NC group parent bodies was characterized by Mo and Ru with variable s-process contributions, but with the two elements always mixed in the same proportions. The CC parent bodies sampled here, by contrast, were derived from a nebular feeding zone that had been mixed to a uniform s-process depleted Mo-Ru isotopic composition. Six molybdenite samples, four glacial diamictites, and two ocean island basalts were analyzed to provide a preliminary constraint on the average Mo isotope composition of the bulk silicate Earth (BSE). Combined results yield an average µ 97Mo value of +3 ± 6. This value, coupled with a previously reported µ 100Ru value of +1 ± 7 for the BSE, indicates that the isotopic composition of the BSE falls precisely on the refined Mo-Ru cosmic correlation. The overlap of the BSE with the correlation implies that there was homogeneous accretion of siderophile elements for the final accretion of 10 to 20 wt% of Earth's mass. The only known cosmochemical materials with an isotopic match to the BSE, with regard to Mo and Ru, are some members of the IAB iron meteorite complex and enstatite chondrites.

Heterogeneous delivery of silicate and metal to the Earth by large planetesimals.

After the Moon's formation, Earth experienced a protracted bombardment by leftover planetesimals. The mass delivered during this stage of late accretion has been estimated to be approximately 0.5% of Earth's present mass, based on highly siderophile element concentrations in the Earth's mantle and the assumption that all highly siderophile elements delivered by impacts were retained in the mantle. However, late accretion may have involved mostly large (≥ 1,500 km in diameter)-and therefore differentiated-projectiles in which highly siderophile elements were sequestered primarily in metallic cores. Here we present smoothed-particle hydrodynamics impact simulations that show that substantial portions of a large planetesimal's core may descend to the Earth's core or escape accretion entirely. Both outcomes reduce the delivery of highly siderophile elements to the Earth's mantle and imply a late accretion mass that may be two to five times greater than previously thought. Further, we demonstrate that projectile material can be concentrated within localized domains of Earth's mantle, producing both positive and negative 182W isotopic anomalies of the order of 10 to 100 ppm. In this scenario, some isotopic anomalies observed in terrestrial rocks can be explained as products of collisions after Moon formation.

Coalescence of Macroscopic Flux Ropes at the Subsolar Magnetopause: Magnetospheric Multiscale Observations.

We report unambiguous in situ observation of the coalescence of macroscopic flux ropes by the magnetospheric multiscale (MMS) mission. Two coalescing flux ropes with sizes of ∼1 R_{E} were identified at the subsolar magnetopause by the occurrence of an asymmetric quadrupolar signature in the normal component of the magnetic field measured by the MMS spacecraft. An electron diffusion region (EDR) with a width of four local electron inertial lengths was embedded within the merging current sheet. The EDR was characterized by an intense parallel electric field, significant energy dissipation, and suprathermal electrons. Although the electrons were organized by a large guide field, the small observed electron pressure nongyrotropy may be sufficient to support a significant fraction of the parallel electric field within the EDR. Since the flux ropes are observed in the exhaust region, we suggest that secondary EDRs are formed further downstream of the primary reconnection line between the magnetosheath and magnetospheric fields.

An ovine hepatorenal fibrocystic model of a Meckel-like syndrome associated with dysmorphic primary cilia and TMEM67 mutations.

Meckel syndrome (MKS) is an inherited autosomal recessive hepatorenal fibrocystic syndrome, caused by mutations in TMEM67, characterized by occipital encephalocoele, renal cysts, hepatic fibrosis, and polydactyly. Here we describe an ovine model of MKS, with kidney and liver abnormalities, without polydactyly or occipital encephalocoele. Homozygous missense p.(Ile681Asn; Ile687Ser) mutations identified in ovine TMEM67 were pathogenic in zebrafish phenotype rescue assays. Meckelin protein was expressed in affected and unaffected kidney epithelial cells by immunoblotting, and in primary cilia of lamb kidney cyst epithelial cells by immunofluorescence. In contrast to primary cilia of relatively consistent length and morphology in unaffected kidney cells, those of affected cyst-lining cells displayed a range of short and extremely long cilia, as well as abnormal morphologies, such as bulbous regions along the axoneme. Putative cilia fragments were also consistently located within the cyst luminal contents. The abnormal ciliary phenotype was further confirmed in cultured interstitial fibroblasts from affected kidneys. These primary cilia dysmorphologies and length control defects were significantly greater in affected cells compared to unaffected controls. In conclusion, we describe abnormalities involving primary cilia length and morphology in the first reported example of a large animal model of MKS, in which we have identified TMEM67 mutations.

The ruthenium isotopic composition of the oceanic mantle.

The approximately chondritic relative, and comparatively high absolute m antle abundances of the highly siderophile elem ents (HSE), suggest that their concentrations in the bulk silicate Earth were primarily established during a final ~0.5 to 1% of "late accretion" to the mantle, following the cessation of core segregation. Consequently, the isotopic composition of the HSE Ru in the mantle reflects an amalgamation of the isotopic compositions of late accretionary contributions to the silicate portion of the Earth. Among cosm ochem ical materials, Ru is characterized by considerable mass-independent isotopic variability, making it a powerful genetic tracer of Earth's late accretionary building blocks. To define the Ru isotopic composition of the oceanic mantle, the largest portion of the accessible mantle, we report Ru isotopic data for materials from one Archean and seven Phanerozoic oceanic m antle domains. A sample from a continental lithospheric mantle domain is also examined. All samples have identical Ru isotopic compositions, within analytical uncertainties, indicating that Ru isotopes are well mixed in the oceanic mantle, defining a µ 100Ru value of 1.2 ± 7.2 (2SD). The only known meteorites with the same Ru isotopic composition are enstatite chondrites and, when corrected for the effects of cosmic ray exposure, mem bers of the Main Group and sLL subgroup of the lAB iron meteorite complex which have a collective CRE corrected µ 100Ru value of 0.9 ± 3.0. This suggests that materials from the region(s) of the solar nebula sampled by these m eteorites likely contributed the dominant portion of late accreted materials to Earth's mantle.

Refinement of high precision Ru isotope analysis using negative thermal ionization mass spectrometry.

A refined method for the isolation, purification, and high precision measurement of Ru isotope compositions in natural samples by negative thermal ionization mass spectrometry (N-TIMS) is reported. After chemical purification of Ru using ion exchange chromatography and microdistillation techniques, the Ru isotopic composition is measured as RuO3- via N-TIMS. Data are corrected for oxide interferences using the simultaneously measured oxygen isotope composition, and subsequently for mass fractionation using an exponential law. Repeat analyses of an Alfa Aesar Ru standard solution demonstrate external reproducibility of 100Ru/101Ru to ±6.4 ppm (2SD). This level of precision is more than two times better than prior techniques. Repeat analyses of gravimetrically prepared mixtures of a natural Alfa Aesar Ru standard and a 100Ru enriched spike show that isotopic differences of ≥13 ppm can be resolved by single measurements of a material using this method. Repeat analyses of diverse terrestrial materials (chromitites and Os-Ir-Ru alloys) are characterized by compositions that are identical to the Alfa Aesar standard, and the external reproducibility for these materials is also identical to that of the chemically pure standard, demonstrating that chemical separation/purification methods introduce no bias to the analysis. These materials likely define the Ru isotopic composition of the Earth's mantle.

GFR may not accurately predict aspects of proximal tubule drug handling.

PURPOSE: Dose modification in renal impairment has traditionally been based on changes in estimated glomerular filtration rate (eGFR; estimated by creatinine clearance). However, many drugs are eliminated by tubular anionic and cationic transport where changes in eGFR may not necessarily reflect changes in tubular function. This study investigated the relationship between GFR and renal tubular function with reference to drug handling by using accepted drug probes. METHODS: Three drug probes, (51)Cr-EDTA, fluconazole, and pindolol, were administered to patients who had varying degrees of renal impairment. Blood sampling, assays, and a pharmacokinetic analysis were performed for all drug probes and endogenous urate. Measured GFR ((51)Cr-EDTA clearance; mGFR) was compared to tubular anionic transport (urate clearance), tubular reabsorption (fluconazole clearance), and tubular cationic transport (S-pindolol clearance). RESULTS: A moderately strong association was demonstrated between the measured isotopic GFR and creatinine clearance (R(2) = 0.78). A moderate positive correlation was found between mGFR and proximal tubular anion transport and reabsorption (R(2) = 0.40-0.44, p < 0.0001). In contrast, cationic secretion correlated poorly with mGFR (R(2) = 0.11, p = 0.036). CONCLUSIONS: Given that drug dosing schedules utilise eGFR values as the basis for modifying drug dosing, our results would suggest that a recommendation of a dose reduction according to eGFR alone should be treated with caution.

Protracted core formation and rapid accretion of protoplanets.

Understanding core formation in meteorite parent bodies is critical for constraining the fundamental processes of protoplanet accretion and differentiation within the solar protoplanetary disk. We report variations of 5 to 20 parts per million in (182)W, resulting from the decay of now-extinct (182)Hf, among five magmatic iron meteorite groups. These (182)W variations indicate that core formation occurred over an interval of ~1 million years and may have involved an early segregation of Fe-FeS and a later segregation of Fe melts. Despite this protracted interval of core formation, the iron meteorite parent bodies probably accreted concurrently ~0.1 to 0.3 million years after the formation of Ca-Al-rich inclusions. Variations in volatile contents among these bodies, therefore, did not result from accretion at different times from an incompletely condensed solar nebula but must reflect local processes within the nebula.

Optimising treatment parameters for Radiofrequency Induced Thermal Therapy (RFiTT): A comparison of the manufacturer's treatment guidance with a locally developed treatment protocol.

OBJECTIVE: Radiofrequency induced Thermal Therapy (RFiTT) is an established endovenous device for the treatment of varicose veins. Our aim was to compare the manufacturer's treatment guidance with a locally developed treatment protocol on early truncal ablation rates between two patient cohorts. METHODS: The study was a retrospective analysis of prospectively collected data from 534 patients treated for incompetent truncal saphenous veins between June 2009 and December 2012. Patients were treated either according to the manufacturer's guidance (Treatment 1), a single pullback rate of ≥1.5 s/cm, or according to local protocol (Treatment 2), repeated vein treatment to visibly occlude the vein lumen. Follow-up at 6 weeks and 12 months included duplex examination, assessment of complications, and pain scores for the first postoperative week. RESULTS: 14 patients did not attend follow-up, leaving 98 patients (142 saphenous trunk treatments) who received Treatment 1 and 422 patients (566 saphenous trunk treatments) who received Treatment 2. The two groups were well matched for age, sex, and preoperative vein parameters. Six week occlusion rates were significantly different, with more treatment failures after Treatment 1 (Treatment 1 5.6% vs. Treatment 2 0.9%; p = .0001). Treatment 1 was more likely to produce incomplete ablation (3.5% vs. 0.9%) and non-ablation (2.1% vs. 0.0%) compared with Treatment 2. No major complications occurred in either group and functional outcomes were otherwise comparable between the two treatment methods. Longer-term follow-up at 12 months in the first 100 patients undergoing Treatment 2 demonstrated maintenance of the early advantage, with partial recanalisations in 9% and 2% for Treatments 1 and 2, respectively. CONCLUSIONS: Six weeks after treatment with RFiTT, a protocol of repeated vein treatments to visibly obliterate the vein lumen produced more reliable venous occlusion compared with manufacturer's guidance. This advantage is maintained at 12 months.

The effect of lipoic acid and vitamin E therapies in individuals with the metabolic syndrome.

The metabolic syndrome is associated with abnormal glucose and lipid metabolism, insulin resistance, increased oxidative stress and pro-inflammatory activity that increase the risk of type 2 diabetes and cardiovascular disease. The aim of this study was to investigate the effect of treatment with the antioxidant α-lipoic acid (ALA) with or without vitamin E supplementation, on markers of insulin resistance and systemic inflammation and plasma nonesterified fatty acid (NEFA) concentrations in individuals with the metabolic syndrome. In a randomized, double-blind, placebo-controlled trial, subjects with the metabolic syndrome received ALA (600 mg/day, n = 34), vitamin E (100 IU/day, n = 36), both ALA and vitamin E (n = 41), or matching placebo (n = 40) for 1 year. Fasting circulating concentrations of glucose and insulin were measure every 3 months and NEFA, markers of inflammation, adiponectin and vitamin E were measured at 6 monthly intervals. Plasma NEFA concentrations decreased [-10 (-18, 0)%] at a marginal level of significance (p = 0.05) in those who received ALA alone compared with placebo and decreased [-8 (-14, -1)% (95% CI)] significantly (P = 0.02) in participants who were randomised to ALA with and without vitamin E compared with those who did not receive ALA. Fasting glucose, insulin, homeostatic model assessment of insulin resistance, adiponectin, and markers of inflammation did not change significantly during the study. These data suggest that prolonged treatment with ALA may modestly reduce plasma NEFA concentrations but does not alter insulin or glucose levels in individuals with the metabolic syndrome.

Rapid passage signals from a vibrationally excited target molecule: a pump and probe experiment with continuous wave quantum cascade lasers.

Two 5 µm continuous wave quantum cascade lasers are used to perform a counterpropagating pump and probe experiment on a low pressure sample of nitric oxide. The strong pump field excites a fundamental rovibrational transition and the weaker probe field is tuned to the corresponding rotationally resolved hot band transition. When both light fields are in resonance, rapid passage is observed in the hot band absorption lineshape arising from a minimally damped and velocity-selected sample of molecules in the v=1 state. The measured rapid passage signals are well described by a two-level model based on the optical Bloch equations.