Electrochemical sensor for human norovirus based on covalent organic framework/pillararene heterosupramolecular nanocomposites.

Noroviruses are the leading cause of acute gastroenteritis and food-borne diseases worldwide. Thus, a rapid, accurate, and easy-to-implement detection method for controlling infection and monitoring progression is urgently needed. In this study, we constructed a novel sandwich-type electrochemical biosensor integrated with two specific recognition elements (aptamer and peptide) for human norovirus (HuNoV). The electrochemical biosensor was fabricated using magnetic covalent organic framework/pillararene heterosupramolecular nanocomposites (MB@Apt@WP5A@Au@COF@Fe3O4) as the signal probes. The sensor showed high accuracy and selectivity. The detection method does not need the extraction and amplification of virus nucleic acid and has a short turn-around time. Intriguingly, the proposed biosensor had a limit of detection of 0.84 copy mL-1 for HuNoV, which was the highest sensitivity among published assays. The proposed biosensor showed higher sensitivity and accuracy compared with immunochromatographic assay in the detection of 98 clinical specimens. The biosensor was capable of determining the predominant infection strain of GII.4 and also GII.3 and achieved 74% selectivity for HuNoV GII group. This study provides a potential method for point-of-care testing and highlights the integrated utilization of Apt and peptide in sensor construction.

Orthostatic effects of midodrine versus L-NAME on cerebral blood flow and the renin-angiotensin-aldosterone system in tetraplegia.

OBJECTIVE: To compare responses to head-up tilt (HUT) in individuals with chronic tetraplegia after midodrine hydrochloride (10 mg) versus nitro-L-arginine methyl ester (L-NAME, 1 mg/kg) administration. DESIGN: Prospective comparative drug trial. SETTING: Veterans Affairs medical center. PARTICIPANTS: Participants (N=7) were studied during 3 laboratory visits: no drug, midodrine (administered orally 30 min before HUT), and L-NAME (infused over a 60-min period). INTERVENTIONS: Anti-hypotensive agents, midodrine, and L-NAME. MAIN OUTCOME MEASURES: Mean arterial pressure (MAP), cerebral blood flow (CBF), and markers of the renin-angiotensin-aldosterone system (RAAS, plasma renin and serum aldosterone) were measured in the supine position at baseline (BL) and during a 45° HUT maneuver. Data were compared between BL and the average of 3 assessments collected during HUT. RESULTS: Orthostatic MAP and CBF were increased with the midodrine and L-NAME groups compared with the no drug trial and the relationship between the change in MAP and CBF was significant (r=0.770; P<0.001). Both L-NAME and midodrine appeared to suppress the post-HUT RAAS response compared with no drug. CONCLUSIONS: Increasing orthostatic blood pressure with L-NAME or midodrine appears to increase CBF and suppress the RAAS during HUT in persons with tetraplegia, although more data are needed to confirm these preliminary findings.

Orthostatic responses to nitric oxide synthase inhibition in persons with tetraplegia.

OBJECTIVES: To determine the effects of 1.0 mg/kg nitro-L-arginine methyl ester (L-NAME) on orthostatic mean arterial pressure (MAP), serum aldosterone, and plasma renin concentrations in persons with chronic tetraplegia compared with nonspinal cord-injured controls. DESIGN: Prospective placebo-controlled intervention study. SETTING: James J. Peters Veterans Affairs Medical Center. PARTICIPANTS: Patients (n=5) with tetraplegia and controls (n=7) participated. The groups were matched for age, height, and weight; the average duration of injury in the tetraplegia group was 22+/-14 years. INTERVENTION: Subjects with tetraplegia visited the laboratory twice, receiving placebo on day 1 and L-NAME (1.0 mg/kg) on day 2. The agents were infused via an intravenous catheter over 60 minutes with the patient in the supine position. Data were collected during the infusion and then during head-up tilt to 45 degrees for 30 minutes. Control subjects visited the laboratory once for placebo infusion and the head-up tilt maneuver. MAIN OUTCOME MEASURE: Orthostatic MAP. RESULTS: Orthostatic MAP was reduced after placebo infusion in subjects with tetraplegia compared with controls (69+/-11 vs 89+/-9 mmHg, respectively; P<.01) and compared with L-NAME infusion (90+/-16 mmHg; P<.01). Orthostatic MAP did not differ when comparing the tetraplegia group with controls after L-NAME infusion. Orthostatic aldosterone levels were increased after placebo compared with L-NAME infusion in persons with tetraplegia; plasma renin levels did not differ among the groups. CONCLUSIONS: These data suggest that nitric oxide synthase inhibition may have clinical potential for treatment of orthostatic hypotension in persons with chronic tetraplegia.

Acute suppression of bone turnover with calcium infusion in persons with spinal cord injury.

BACKGROUND: Some people with chronic spinal cord injury (SCI) have low vitamin D levels and secondary hyperparathyroidism. OBJECTIVE: To determine whether, and to what extent, an acute calcium infusion decreased levels of N-telopeptide (NTx), a marker of osteoclastic activity, in individuals with chronic SCI. STUDY DESIGN: Case series. SUBJECTS: Eight men with chronic SCI. A relatively low serum 25 hydroxyvitamin D concentration (25[OH]D < or =20 ng/mL) and/or a high parathyroid hormone (PTH) (>55 pg/mL) was a prerequisite for study inclusion. METHODS: Calcium gluconate bolus 0.025 mmol elemental calcium/kg over 20 minutes followed by a constant infusion of 0.025 mmol/kg per hour for 6 hours was infused; blood samples were collected every 2 hours for measurement of serum total calcium, creatinine, NTx, and PTH. RESULTS: All results are expressed as means (+/- SDs). Baseline serum 25-hydroxyvitamin D level was 14.5 +/- 3.5 ng/mL (range: 10.2-19.6 ng/mL); PTH, 70 +/- 25 pg/mL (range: 37-100 pg/mL); and NTx, 21 +/- 7 nM bone collagen equivalents (BCE) (range: 14-34 nM). At 2, 4, and 6 hours after the calcium infusion, serum calcium rose from 9.3 +/- 0.2 to 10.8 +/- 0.9, 10.5 +/- 0.8, and 10.6 +/- 0.6 mg/d; PTH was suppressed from 70 +/- 25 pg/mL to 18 +/- 12, 16 +/- 9, and 15 +/- 9 pg/mL, respectively; NTx fell from 21 +/- 8 nM BCE to 17 +/- 5, 12 +/- 4, and 12 +/- 3 nM BCE, respectively. CONCLUSIONS: Serum NTx is a marker for bone collagen catabolism, and its reduction suggests that bone turnover was decreased. A relative deficiency of vitamin D associated with chronically elevated levels of PTH would be expected to increase bone turnover and to worsen the bone loss associated with immobilization.

Provocative stimulation of growth hormone: a monozygotic twin study discordant for spinal cord injury.

BACKGROUND/OBJECTIVE: A blunted growth hormone (GH) response to provocative testing and/or low levels of plasma insulin-like growth factor-I (IGF-I) have been reported in persons with spinal cord injury (SCI). A reduction in activity of the GH-IGF-I axis may have deleterious effects on body composition and function. Provocative testing for GH stimulation was performed to determine the response in monozygotic twins that were discordant for SCI. METHODS: GH stimulation testing was performed by the administration of intravenous arginine. RESULTS: Nine SCI twins with paraplegia, a mean age of 39 +/- 9 years, and duration of injury of 14 +/- 9 years were studied. The twins with SCI had a significantly lower body mass index than non-SCI twins (22.5 +/- 4.0 vs 25.1 +/- 4.2 kg/m2; P < 0.05); percent fat mass was greater in the twins with SCI (30 +/- 11% vs 22 +/- 10%; P < 0.05). Baseline serum GH was correlated with percent fat only in the SCI twins. The response to GH provocative stimulation was less in the twins with SCI: peak GH response was 5.8 +/- 6.6 vs 13.0 +/- 7.3 ng/mL (P < 0.05), and sum GH response was 15.7 +/- 15.6 vs 30.2 +/- 17.3 ng/mL (P = 0.06). Although baseline serum GH was correlated with stimulated response in the SCI twins, this relationship was not found in the non-SCI twins. Adiposity was positively related to the provocative serum GH response in twins with SCI rather than negatively related, as noted in the non-SCI twins. CONCLUSIONS: This study confirms and extends prior work that reported a reduction in stimulated GH release in persons with SCI, which was related to baseline values.

Effect of low-dose baclofen administration on plasma insulin-like growth factor-I in persons with spinal cord injury.

Patients with chronic spinal cord injury (SCI), a condition associated with reduced physical function, have been reported to have lower plasma insulin-like growth factor-I (IGF-I) levels than able-bodied persons. We evaluated the potential for daily low-dose baclofen administered over several weeks to increase plasma IGF-I levels. Ten healthy male outpatients with chronic SCI were studied prospectively. Patients received escalating doses of baclofen for 4 weeks at each dose level (5, 10, and 20 mg/d). At each dose of baclofen, an increase in the plasma IGF-I was noted; significant increases in plasma IGF-I occurred at 2 weeks after administration of drug at doses of 10 and 20 mg/d, with a subsequent rise to peak levels on baclofen 20 mg/d [baseline, 205+/-74; peak, 218+/-76 (not significant), 239+/-83 (P<.05), 263+/-87 microg/L (P<.05), at baclofen 5, 10, and 20 mg/d, respectively]. In conclusion, low-dose baclofen administration for 4 weeks stimulated the growth hormone-IGF-I axis in persons with SCI, with the potential for beneficial effects on body composition.

Facile synthesis of hierarchical and porous V2O5 microspheres as cathode materials for lithium ion batteries.

Hierarchical and porous V2O5 microspheres have been fabricated by a refluxing approach followed by annealing in air. The resulting porous V2O5 microspheres typically have diameters of 3-6 µm and are constructed of intertwined laminar nanocrystals or crosslinked nanobricks. It is found that the vanadyl glycolates rinsed with water have pronounced pore structures than that rinsed with ethanol alone. In addition, the configuration of the vanadyl glycolates microspheres can be tuned during the refluxing along with stirring. The possible formation processes of the vanadyl glycolates and V2O5 products have been discussed based on the experimental data. Electrochemical tests indicate that the hierarchical and porous V2O5 microspheres exhibit relatively high and stable Li(+) storage properties. The porous V2O5 microspheres assembled by intertwined nanoparticles maintain reversible Li(+) storage capacities of 102 and 80 mAh g(-1), respectively; whilst the porous V2O5 microspheres assembled by crosslinked nanobricks maintain reversible Li(+) storage capacities of 100 and 85 mAh g(-1) over 100 cycles at current rates of 0.5 and 1 C, respectively. The superior Li(+) storage performance of the hierarchical and porous V2O5 microspheres could mainly be ascribed to the improved electrode/electrolyte interface, reduced Li(+) diffusion paths, and relieved volume variation during lithiation and delithiation processes.

Effect of a vitamin D analog on leg bone mineral density in patients with chronic spinal cord injury.

A randomized, placebo-controlled trial was performed to determine the effect of a vitamin D analog (1-alpha-hydroxyvitamin D(2) [1-alpha D(2)]) on the bone mineral density (BMD) in patients with chronic spinal cord injury (SCI). Forty subjects with chronic complete motor SCI were enrolled. The mean plus or minus standard deviation age and duration of injury were 42 plus or minus 12 yr and 11 plus or minus 10 yr, respectively. Either 4 micrograms 1-alpha D(2) (n = 19) or placebo (n = 21) was administered daily for 24 mo. Metabolic markers of bone resorption and formation were obtained. Regional lower-limb dual-energy x-ray absorptiometry was performed at baseline and at 6, 12, 18, and 24 mo. Leg BMD and percent change from baseline significantly increased at 6 (percent change only), 12, 18, and 24 mo in the treatment group, but not in the placebo group. Urinary N-telopeptide, a marker of bone resorption, was significantly reduced during treatment with 1-alpha D(2), but markers of bone formation were not changed.