Positron interactions with water-total elastic, total inelastic, and elastic differential cross section measurements.

Utilising a high-resolution, trap-based positron beam, we have measured both elastic and inelastic scattering of positrons from water vapour. The measurements comprise differential elastic, total elastic, and total inelastic (not including positronium formation) absolute cross sections. The energy range investigated is from 1 eV to 60 eV. Comparison with theory is made with both R-Matrix and distorted wave calculations, and with our own application of the Independent Atom Model for positron interactions.

Return-to-duty rates among coalition forces treated in a forward-deployed pain treatment center: a prospective observational study.

BACKGROUND: Non-battle-related injuries and the recurrence of chronic pain are major causes of medical evacuation in wartime. Because a pain medicine specialist may or may not be assigned to a forward-deployed medical unit, the treatment of pain from non-battle-related injuries in war zones is a serendipitous endeavor. Previous studies have demonstrated that the return-to-unit rate for soldiers evacuated to a tertiary care facility for pain management is abysmally low. METHODS: This is a prospective, observational study measuring return-to-duty rates in the first forward-deployed pain treatment center. RESULTS: Over a 6-month period, 132 patients were treated, the large majority (n = 113) of whom were coalition forces. In descending order, the four most common diagnoses among coalition forces were lumbar radiculopathy (n = 63), thoracic pain (n = 13), cervical radiculopathy (n = 8), and groin pain (n = 8). Epidural steroid injections (n = 125) were by far the most frequently performed procedure, followed by trigger point injections (n = 21), lumbar facet blocks (n = 16), and groin blocks (n = 9). Nonsteroidal antiinflammatory drugs were prescribed to 70% of patients, and 24% were referred to physical therapy. The return-to-duty rate for coalition forces was 94.7%. The primary complaint of all 7 patients who required medical evacuation outside the theaters of operation was groin pain. CONCLUSIONS: These results demonstrate the feasibility of obtaining high return-to-duty rates when aggressive pain management strategies are used in forward-deployed areas.

Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels.

BACKGROUND: Although abnormal L-arginine NO signaling contributes to endothelial dysfunction in the aging cardiovascular system, the biochemical mechanisms remain controversial. L-arginine, the NO synthase (NOS) precursor, is also a substrate for arginase. We tested the hypotheses that arginase reciprocally regulates NOS by modulating L-arginine bioavailability and that arginase is upregulated in aging vasculature, contributing to depressed endothelial function. METHODS AND RESULTS: Inhibition of arginase with (S)-(2-boronoethyl)-L-cysteine, HCl (BEC) produced vasodilation in aortic rings from young (Y) adult rats (maximum effect, 46.4+/-9.4% at 10(-5) mol/L, P<0.01). Similar vasorelaxation was elicited with the additional arginase inhibitors N-hydroxy-nor-L-arginine (nor-NOHA) and difluoromethylornithine (DFMO). This effect required intact endothelium and was prevented by 1H-oxadiazole quinoxalin-1-one (P<0.05 and P<0.001, respectively), a soluble guanylyl cyclase inhibitor. DFMO-elicited vasodilation was greater in old (O) compared with Y rat aortic rings (60+/-6% versus 39+/-6%, P<0.05). In addition, BEC restored depressed L-arginine (10(-4) mol/L)-dependent vasorelaxant responses in O rings to those of Y. Arginase activity and expression were increased in O rings, whereas NOS activity and cyclic GMP levels were decreased. BEC and DFMO suppressed arginase activity and restored NOS activity and cyclic GMP levels in O vessels to those of Y. CONCLUSIONS: These findings demonstrate that arginase modulates NOS activity, likely by regulating intracellular L-arginine availability. Arginase upregulation contributes to endothelial dysfunction of aging and may therefore be a therapeutic target.

Herpes zoster-associated severity and duration of pain, health-related quality of life, and healthcare utilization in Taiwan: a prospective observational study.

BACKGROUND: To assess the severity and duration of herpes zoster (HZ)-associated pain (ZAP) and its impact on quality of life (QoL) and healthcare utilization (HCRU) from a patient perspective in routine care in Taiwan. METHODS: A prospective, observational, single-cohort study was conducted in five centers across Taiwan. Patients were recruited at different time points during their HZ episode and were followed for ≤180 days. ZAP was assessed with the Initial Zoster Impact Questionnaire and the Zoster Brief Pain Inventory, QoL with the EQ-5D, and HCRU with a simple questionnaire. RESULTS: A total of 150 patients were included with a mean age of 64.9 years and mean time since rash onset of 18.8 days. Prodromal pain was experienced by 64.7% of patients, of whom 91.8% reported moderate-to-severe pain. At enrollment, 98.0% of patients experienced ZAP. Mean ± SD worst pain score decreased from 5.95 ± 3.09 at enrollment to 2.65 ± 2.98 at 30 days and 0.28 ± 0.83 at 180 days. Postherpetic neuralgia was observed in 20.7% of patients. Mean ± SD EQ-5D score significantly decreased (P < 0.001) from 0.91 ± 0.16 before rash onset to 0.67 ± 0.18 after rash onset, showing significant QoL deterioration up to 60 days. The impact of HZ on QoL and pain severity was similar across age groups. Significant HCRU was observed including visits to the doctor (83.3% of patients), specialist (30.7%), emergency department (24.7%), physiotherapist (23.3%), and hospitalizations (20.7%). CONCLUSION: Severe morbidity and significant HCRU are associated with HZ in Taiwan, supporting the need for early intervention and preventive strategies to reduce the HZ-associated burden of illness.

On the use of Monte Carlo simulations to model transport of positrons in gases and liquids.

In this paper we make a parallel between the swarm method in physics of ionized gases and modeling of positrons in radiation therapy and diagnostics. The basic idea is to take advantage of the experience gained in the past with electron swarms and to use it in establishing procedures of modeling positron diagnostics and therapy based on the well-established experimental binary collision data. In doing so we discuss the application of Monte Carlo technique for positrons in the same manner as used previously for electron swarms, we discuss the role of complete cross section sets (complete in terms of number, momentum and energy balance and tested against measured swarm parameters), we discuss the role of benchmarks and how to choose benchmarks for electrons that may perhaps be a subject to experimental verification. Finally we show some samples of positron trajectories together with secondary electrons that were established solely on the basis of accurate binary cross sections and also how those may be used in modeling of both gas filled traps and living organisms.

Burden of illness, quality of life, and healthcare utilization among patients with herpes zoster in South Korea: a prospective clinical-epidemiological study.

OBJECTIVES: To assess the herpes zoster (HZ) disease burden, including the severity and duration of HZ-associated pain, its impact on quality of life (QoL), and healthcare resource utilization (HCRU) in a South Korean clinical setting. METHODS: Patients aged ≥50 years were followed prospectively for ≤6 months. Based on the duration of their episode at enrollment, cases were classified as incident (<7 days) or prevalent (≥7 days). HZ pain and discomfort were measured with the HZ Severity of Illness (HZ-SOI) severity-by-duration composite score. RESULTS: One hundred fifty-one patients (69.5% prevalent cases) were enrolled. Prodrome pain was experienced by 68.2% of patients, of whom 95.1% experienced moderate-to-severe pain; post-herpetic neuralgia was experienced by 38.4%. Prevalent disease, higher acute pain, and older age were significant predictors of greater HZ-SOI, while use of antivirals was associated with decreased HZ-SOI. HZ-associated pain was associated with reduced QoL and affected all daily living activities (particularly mood, life enjoyment, general activities, and sleep), resulting in significant HCRU, including primary care doctor, specialist, or physiotherapist consultations, hospitalizations, and emergency department visits. CONCLUSION: Severe morbidity, impaired QoL, and significant HCRU are associated with HZ in South Korea, especially in older patients, supporting the need for early intervention and preventive strategies to reduce the HZ-associated disease burden.

Work and productivity loss related to herpes zoster.

OBJECTIVE: To estimate absenteeism and presenteeism-related work loss due to herpes zoster (HZ) among working individuals of 50-64 years of age. METHODS: This telephone survey included individuals with ≥1 insurance claim for HZ in the past year in administrative claims data from five US commercial health plans. Demographic information, characteristics of the HZ episode; impact of HZ on activities of daily living (ADL), and work days loss and productivity were surveyed. RESULTS: Responses were obtained from 153 of 1654 individuals who were contacted and were eligible for the survey (9.3%). Most had moderate or severe HZ (72.6%). Close to two-thirds reported some impact of HZ on ADL such as shopping, housework/chores, and social engagement. About half (51%) reported missing work due to HZ, and about an equal percentage reported little or much worse productivity than usual due to HZ while at work. On average, age-adjusted absenteeism- and presenteeism-related work loss was estimated at 31.6 hours, and 84.4 hours, respectively, with a combined work loss of 116.0 hours per HZ episode in a working person of 50-64 years of age. Work loss tended to increase with age and the duration and severity of the HZ episode. CONCLUSIONS: The study documents a substantial societal burden of HZ-related work and productivity loss. This is important information to take into consideration, in addition to the direct medical burden, when making policy decisions around vaccine prevention of HZ. LIMITATIONS: The study may potentially be subject to selection bias due to low survey response rate and since only those cases who sought care for a HZ episode were captured. The study may also be subject to respondent recall bias. Finally, since some respondents could still be having the HZ episode at the time of survey, the study may potentially have under-estimated the work and productivity loss.

Discovery and in vitro/in vivo studies of tetrazole derivatives as Kv1.5 blockers.

A novel class of tetrazole-derived Kv1.5 blockers is disclosed. In in vitro studies, several compounds had IC(50)s ranging from 180 to 550 nM. In vivo studies indicated that compounds 2f and 2j increased right atrial ERP about 40% without affecting ventricular ERP.

Synthesis and evaluation of (2-phenethyl-2H-1,2,3-triazol-4-yl)(phenyl)methanones as Kv1.5 channel blockers for the treatment of atrial fibrillation.

A series of novel (2-phenethyl-2H-1,2,3-triazol-4-yl)(phenyl)methanones were prepared and examined for utility as Kv1.5 channel blockers for the treatment of atrial fibrillation.