Introduction and scaling up of new drugs for drug-resistant TB: experiences from the Americas.

The number of multidrug-resistant tuberculosis (MDR-TB) cases reported in the Americas has increased by 21.2%, from 3737 in 2016 to 4791 in 2018. The WHO has been recommending changes on the treatment of DR-TB, moving from long-duration treatment with injectables to a short oral regimen with new drugs such as bedaquiline (BDQ) and delamanid (DLM), in selected cases and only under programmatic conditions. Injectables are no longer recommended by the WHO due to lower efficacy and the increasing seriousness of adverse events. The introduction of new oral drugs for DR-TB received a boost with a global donation of BDQ to some eligible countries, which continues with the countries purchasing drugs through the Pan American Health Organization Strategic Fund. The main challenges in the scaling up of new drugs for DR-TB include low DR-TB detection rate, the slow pace in transitioning to molecular testing and delays in the introduction of new oral short regimens for MDR-TB. The Americas need to accelerate the scale up of new oral treatments, improve detection rates, increase molecular diagnosis of resistance, and ensure the registration and introduction of the shorter treatment regimen in national MDR-TB guidelines.

Simulated Seasonal Photoperiods and Fluctuating Temperatures Have Limited Effects on Blood Feeding and Life History in Aedes triseriatus (Diptera: Culicidae).

Biotic and abiotic factors change seasonally and impact life history in temperate-zone ectotherms. Temperature and photoperiod are factors that change in predictable ways. Most studies testing for effects of temperature on vectors use constant temperatures and ignore potential correlated effects of photoperiod. In two experiments, we tested for effects of larval rearing environments creating ecologically relevant temperatures and photoperiods simulating early and late season conditions (June and August), or constant temperatures (cool and warm) with the June or August photoperiods, respectively. We determined effects on survivorship, development, size, and a composite performance index in a temperate-zone population of Aedes triseriatus (Say). We followed cohorts of resulting females, all held under the same environmental conditions, to assess carry-over effects of rearing conditions for larvae on longevity, blood feeding, and egg production. Larval survivorship was affected by treatment in one experiment. Development time was greater in the June and cool treatments, but the constant and fluctuating temperatures did not differ. Significantly larger mosquitoes were produced in fluctuating versus constant temperature treatments. There were no significant treatment effects on the composite performance index. Adult female longevity was lower after rearing at constant versus fluctuating temperature, but there was no difference between June and August, nor did size affect longevity. There was no effect of treatments on blood feeding and a limited effect on egg production. We conclude that seasonal temperatures and photoperiods during development have limited effects on this population of A. triseriatus and find little evidence of strong effects of fluctuating versus constant temperatures.

Luteinizing hormone receptor knockout (LuRKO) mice and transgenic human chorionic gonadotropin (hCG)-overexpressing mice (hCG alphabeta+) have bone phenotypes.

Considerable attention has been paid to the role of sex steroids during periods of major skeletal turnover, but the interaction of the gonadotropic hormones, which include LH, FSH, and human chorionic gonadotropin (hCG), within bone tissue have been overlooked. The question is pertinent due to the recent detection of extragonadal expression of gonadotropin receptors. Western blotting, immunolocalization, and RT-PCR supported the presence of osteoblast LH receptors. However, osteoblast cells failed to bind [(125)I]hCG and treatment with hCG failed to generate either cAMP or phosphorylated ERK 1/2. Bone mineral density (BMD) and bone histomorphometry were examined in the following models: 1) LH receptor null mutant (LuRKO) mice; 2) transgenic mice overexpressing hCG (hCG alphabeta+); and 3) ovariectomized (OVX) hCG alphabeta+ model. Male LuRKO mice showed a decrease in BMD after 5 months, apparently secondary to suppressed gonadal steroid production. Similarly, 9- to 10-wk-old female LuRKO mice exhibited decreases in histomorphometric parameters tested. The data indicate that loss of LH signaling results in a reduction in bone formation or an increase in bone resorption. By contrast, there were significant increases in BMD and histomorphometric indices for female, but not male, hCG alphabeta+ mice, indicating that chronic exposure to hCG results in bone formation or a decrease in bone resorption. However, OVX of the hCG alphabeta+ mice resulted in a significant reduction in BMD comparable to OVX WT controls. Although gonadotropin levels are tightly linked to sex steroid titers, it appears that their effects on the skeleton are indirect.

A method for reviewing radio-telemetry paramedic calls.

A method is presented for reviewing the taped radio-telemetry records of paramedic calls managed by hospital-based emergency medicine residents. All paramedic calls to the LAC/USC base station are reviewed by an emergency medicine resident using a special tape review form which focuses on communication skills, initial paramedic field assessment, sense of urgency of the case, and the completeness of the filed report. Additional emphasis is placed on the base station physician's interpretation of the field presentation and his choice of therapy. Tapes demonstrating particular skills or pitfalls in prehospital management are selected for monthly tape review conferences. Such conferences provide a method by which each side of the prehospital care team can perceive the position of the other, encouraging physicians and paramedics to enhance their respective roles in providing effective prehospital emergency care.