The Continuing Challenges of Leprosy SCOLLARD, D. M; ADAMS, L. B; GILLIS, T. P ...
Clinical Microbiology Reviews,
04/2006, Letnik:
19, Številka:
2
Journal Article
Context: Physical frailty is associated with reduced muscle strength, impaired physical function, and quality of life. Testosterone (T) increases muscle mass and strength in hypogonadal patients. It ...is unclear whether T has similar effects in intermediate-frail and frail elderly men with low to borderline-low T.
Objective: Our objective was to determine the effects of 6 months T treatment in intermediate-frail and frail elderly men, on muscle mass and strength, physical function, and quality of life.
Design and Setting: We conducted a randomized, double-blind, placebo-controlled, parallel-group, single-center study.
Participants: Participants were community-dwelling intermediate-frail and frail elderly men at least 65 yr of age with a total T at or below 12 nmol/liter or free T at or below 250 pmol/liter.
Methods: Two hundred seventy-four participants were randomized to transdermal T (50 mg/d) or placebo gel for 6 months. Outcome measures included muscle strength, lean and fat mass, physical function, and self-reported quality of life.
Results: Isometric knee extension peak torque improved in the T group (vs. placebo at 6 months), adjusted difference was 8.6 (95% confidence interval, 1.3–16.0; P = 0.02) Newton-meters. Lean body mass increased and fat mass decreased significantly in the T group by 1.08 ± 1.8 and 0.9 ± 1.6 kg, respectively. Physical function improved among older and frailer men. Somatic and sexual symptom scores decreased with T treatment; adjusted difference was −1.2 (−2.4 to −0.04) and −1.3 (−2.5 to −0.2), respectively.
Conclusions: T treatment in intermediate-frail and frail elderly men with low to borderline-low T for 6 months may prevent age-associated loss of lower limb muscle strength and improve body composition, quality of life, and physical function. Further investigations are warranted to extend these results.
Treatment with testosterone of intermediate-frail and frail elderly men with low to borderline-low testosterone levels for 6 months may prevent age-associated loss of lower limb muscle strength and improve body composition, quality of life, and physical function.
Light‐emitting electrochemical cells (LECs) are devices that utilize efficient ion redistribution to produce high‐efficiency electroluminescence in a simple device architecture. Prototypical polymer ...LECs utilize three components in the active layer: a luminescent conducting polymer, a salt, and an electrolyte. Similarly, many small‐molecule LECs also utilize an electrolyte to disperse salts. In these systems, the electrolyte is incorporated to efficiently conduct ions and to maintain phase compatibility between all components. However, certain LEC approaches and materials systems enable device operation without a dedicated electrolyte. This review describes the general methods and materials used to circumvent the use of a dedicated electrolyte in LECs. The techniques of synthetically coupling electrolytes, incorporating ionic liquids, and introducing inorganic salts are presented in view of research efforts to date. The use of these techniques in emerging classes of light‐emitting electrochemical cells is also discussed. These approaches have yielded some of the most efficient, long‐lasting, and commercially applicable LECs to date.
Maintaining ionic conductivity in the active films of light‐emitting electrochemical cells is essential to their operation, and many devices use dedicated electrolytes such as poly(ethylene oxide). This review describes the approaches to avoid the use of dedicated electrolyte materials in light‐emitting electrochemical cells through clever combinations of electroluminescent materials and associated salts.
Summary
In a phase 2 open‐label study of the novel proteasome inhibitor bortezomib, 54 patients with multiple myeloma who had relapsed after or were refractory to frontline therapy were randomized to ...receive intravenous 1·0 or 1·3 mg/m2 bortezomib twice weekly for 2 weeks, every 3 weeks for a maximum of eight cycles. Dexamethasone was permitted in patients with progressive or stable disease after two or four cycles respectively. Responses were determined using modified European Group for Blood and Marrow Transplantation criteria. The complete response (CR) + partial response (PR) rate for bortezomib alone was 30% 90% confidence interval (CI), 15·7–47·1 and 38% (90% CI, 22·6–56·4) in the 1·0 mg/m2 (8 of 27 patients) and 1·3 mg/m2 (10 of 26 patients) groups respectively. The CR + PR rate for patients who received bortezomib alone or in combination with dexamethasone was 37% and 50% for the 1·0 and 1·3 mg/m2 cohorts respectively. The most common grade 3 adverse events were thrombocytopenia (24%), neutropenia (17%), lymphopenia (11%) and peripheral neuropathy (9%). Grade 4 events were observed in 9% (five of 54 patients). Bortezomib alone or in combination with dexamethasone demonstrated therapeutic activity in patients with multiple myeloma who relapsed after frontline therapy.
Orthodontic patients have an increased risk of white-spot lesion formation. A clinical trial was conducted to test whether, in a post-orthodontic population using fluoride toothpastes and receiving ...supervised fluoride mouthrinses, more lesions would regress in participants using a remineralizing cream containing casein phosphopeptide- amorphous calcium phosphate compared with a placebo. Forty-five participants (aged 12–18 yrs) with 408 white-spot lesions were recruited, with 23 participants randomized to the remineralizing cream and 22 to the placebo. Product was applied twice daily after fluoride toothpaste use for 12 weeks. Clinical assessments were performed according to ICDAS II criteria. Transitions between examinations were coded as progressing, regressing, or stable. Ninety-two percent of lesions were assessed as code 2 or 3. For these lesions, 31% more had regressed with the remineralizing cream than with the placebo (OR = 2.3, P = 0.04) at 12 weeks. Significantly more post-orthodontic white-spot lesions regressed with the remineralizing cream compared with a placebo over 12 weeks.
We combine thermal electron densities in Mars' ionosphere with magnetic topology information to investigate the sources of the nightside ionosphere. Thermal electron density is measured in situ by ...the Langmuir Probe and Waves experiment onboard Mars Atmospheric and Volatile EvolutioN, while magnetic topology is simultaneously inferred from suprathermal electron energy‐pitch angle distributions measured by the Solar Wind Electron Analyzer and the Magnetometer. Topologically closed regions inhibit electron impact ionization, allowing us to isolate the effects of plasma transport from the dayside, which exhibits a dawn‐dusk asymmetry. Pressure gradient forces on open magnetic field lines connected to the dayside ionosphere source the high‐altitude nightside ionosphere, resulting in higher densities. Regions that are topologically open to the nightside ionosphere allow us to assess in situ production by electron impact ionization, which is responsible for ~50% of the nightside ionosphere below ~160 km and ~25% above ~220 km (on average).
Plain Language Summary
Mars' dayside ionosphere is produced by ionization of the neutral atmosphere by solar extreme ultraviolet and X‐ray photons. This photoionization source is absent at night, so the nightside ionosphere must be supplied by plasma transport from day to night or created in situ by impact ionization caused by the precipitation of energetic electrons onto the neutral atmosphere. In this study, we use measurements from the Mars Atmospheric and Volatile EvolutioN spacecraft to identify these sources and estimate their contributions to the nightside ionosphere. At altitudes below ~160 km, electron impact ionization accounts for half of the nightside ionosphere, with the other half supplied by transport from the dayside via collisional coupling with neutral winds. At higher altitudes, the nightside plasma density is found to be higher when it is directly supplied by transport from the dayside ionosphere.
Key Points
At low altitudes ion motion collisionally couples to neutral winds, sourcing the nightside ionosphere asymmetrically from dawn and dusk
On open field lines connected to the dayside, the nightside ionosphere is sourced by dayside plasma via pressure gradient forces
On average, electron impact ionization produces ~50% of Mars' nightside ionospheric plasma below ~160 km and ~25% above 220 km
To evaluate published evidence of efficacy and safety of pharmacologic treatments for childhood spasticity due to cerebral palsy.
A multidisciplinary panel systematically reviewed relevant literature ...from 1966 to July 2008.
For localized/segmental spasticity, botulinum toxin type A is established as an effective treatment to reduce spasticity in the upper and lower extremities. There is conflicting evidence regarding functional improvement. Botulinum toxin type A was found to be generally safe in children with cerebral palsy; however, the Food and Drug Administration is presently investigating isolated cases of generalized weakness resulting in poor outcomes. No studies that met criteria are available on the use of phenol, alcohol, or botulinum toxin type B injections. For generalized spasticity, diazepam is probably effective in reducing spasticity, but there are insufficient data on its effect on motor function and its side-effect profile. Tizanidine is possibly effective, but there are insufficient data on its effect on function and its side-effect profile. There were insufficient data on the use of dantrolene, oral baclofen, and intrathecal baclofen, and toxicity was frequently reported.
For localized/segmental spasticity that warrants treatment, botulinum toxin type A should be offered as an effective and generally safe treatment (Level A). There are insufficient data to support or refute the use of phenol, alcohol, or botulinum toxin type B (Level U). For generalized spasticity that warrants treatment, diazepam should be considered for short-term treatment, with caution regarding toxicity (Level B), and tizanidine may be considered (Level C). There are insufficient data to support or refute use of dantrolene, oral baclofen, or continuous intrathecal baclofen (Level U).
Lap joints are used extensively in the manufacture of cars. In order to determine the effect of using a structural adhesive instead of spot-welding, a detailed series of tests and finite element ...analyses were conducted using a range of loadings. The adhesive was a toughened epoxy and the adherend was mild steel typical of that used in the manufacture of car bodyshells. The lap joints were tested in tension (which creates shear across the bondline), four-point loading (pure bending) and three-point loading (bending plus shear). Various parameters were investigated such as the overlap length, the bondline thickness and the spew fillet. The major finding is that three-point bending and tension loading are very similar in the way in which they affect the adhesive while the four-point bend test does not cause failure because the steel yields before the joint fails. A failure criterion has been proposed based on the tensile load and bending moment applied to the joint.
Evidence is strengthening for the morphological evaluation of tumor infiltrating lymphocytes (TILs) in breast cancer. Herein, the concepts for TILs assessment are laid out by pathologists to ...facilitate their wider evaluation and consistent interpretation. The goal of this article is to promote the evaluation of TILs as a biomarker in research, clinical trial settings and day-to-day practice.
The morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is gaining momentum as evidence strengthens for the clinical relevance of this immunological biomarker. Accumulating evidence suggests that the extent of lymphocytic infiltration in tumor tissue can be assessed as a major parameter by evaluation of hematoxylin and eosin (H&E)-stained tumor sections. TILs have been shown to provide prognostic and potentially predictive value, particularly in triple-negative and human epidermal growth factor receptor 2-overexpressing BC.
A standardized methodology for evaluating TILs is now needed as a prerequisite for integrating this parameter in standard histopathological practice, in a research setting as well as in clinical trials. This article reviews current data on the clinical validity and utility of TILs in BC in an effort to foster better knowledge and insight in this rapidly evolving field, and to develop a standardized methodology for visual assessment on H&E sections, acknowledging the future potential of molecular/multiplexed approaches.
The methodology provided is sufficiently detailed to offer a uniformly applied, pragmatic starting point and improve consistency and reproducibility in the measurement of TILs for future studies.
The United States has the highest incarceration rate in the world. Incarceration can increase HIV risk behaviors for individuals involved with the criminal justice system and may be a driver of HIV ...acquisition within the community.
We used an agent-based model to simulate HIV transmission in a sexual-contact network representing heterosexual African American men and women in Philadelphia to identify factors influencing the impact of male mass incarceration on HIV acquisition in women. The model was calibrated using surveillance data and assumed incarceration increased the number of sexual contacts and decreased HIV care engagement for men post-release. Incarceration of a partner increased the number of sexual contacts for women. We compared a counterfactual scenario with no incarceration to scenarios varying key parameters to determine what factors drove HIV acquisition in women.
Setting the duration of male high-risk sexual behavior to two years post-release increased the number of HIV transmissions to women by more than 20%. Decreasing post-release HIV care engagement and increasing HIV acquisition risk attributable to sexually transmitted infections (STIs) also increased the number of HIV transmissions to women. Changing the duration of risk behavior for women, the proportion of women engaging in higher risk behavior, and the relative risk of incarceration for HIV-infected men had minimal impact.
The mass incarceration of African American men can increase HIV acquisition in African American women on a population-level through factors including post-release high-risk behaviors, disruption of HIV care engagement among formerly incarcerated men, and increased STI prevalence. These findings suggest that the most influential points of intervention may be programs seeking to reduce male risk behaviors and promote HIV care engagement post-release, as well as STI testing and treatment programs for recently incarcerated men, as well as women with incarcerated partners.