Medicinal Cannabis Use in Sickle Cell Anemia

Approximately 100,000 Americans suffer from sickle cell anemia (SCA), a severe hereditary form of anemia in which red blood cells can mutate into a sickled shape causing severe pain crises that can lead to ED visits, hospitalization, and negatively impact multiple organ systems. Pain crises greatly impact the quality of life for SCA patients. Living with SCA can be stressful and often affects patients’ mental health, causing anxiety or depression (National Heart, Lung, and Blood Institute, 2016). Opioids have been a treatment mainstay for the severe pain caused by SCA but the side effects of opioids, plus the risk of dependence, are issues that have led both patients and researchers to consider medicinal cannabis as a treatment option. While there is limited research addressing the treatment of sickle cell pain with cannabis some research does suggest that cannabis could have a beneficial effect on the management of both chronic pain and acute pain (Choo, Feldstein Ewing, & Lovejoy, 2016; Kroenke & Cheville, 2017). The aim of this study is to evaluate the association between medicinal cannabis use and quality of life for individuals with SCA. The primary goal of this pilot study is to gather a cohort of participants and administer a baseline survey that will be used in a larger study. The goal of the larger study is to assess the impact of medicinal cannabis available through Pennsylvania’s Department of Health-approved dispensaries in Philadelphia on the quality of life for individuals with sickle cell anemia (SCA)

First report of anthelmintic resistance in Haemonchus contortus in alpacas in Australia

BACKGROUND: Parasitic nematodes can cause substantial clinical and subclinical problems in alpacas and anthelmintics are regularly used to control parasitic nematodes in alpacas. Although anthelmintic resistance has been reported in ruminants worldwide, very little is known about anthelmintic resistance in alpacas. The present study was carried out to confirm a suspected case of anthelmintic resistance in Haemonchus contortus in alpacas in Australia. METHODS: Post mortem examination of an alpaca was conducted to determine the cause of its death. To confirm a suspected case of macrocyclic lactone (ML) resistance in H. contortus in alpacas, a faecal egg count reduction test (FECRT) was performed using closantel (7.5 mg/kg) and ivermectin (0.2 mg/kg). Nematode species were identified by morphological and molecular methods. RESULTS: Post mortem examination of a 1-year-old female alpaca that had died following a brief period of lethargy, anorexia and recumbency revealed severe anaemia, hypoproteinaemia and gastric parasitism by adult Haemonchus contortus, despite recent abamectin (0.2 mg/kg) treatment. Based on these findings and the exclusive use of MLs in the herd over the preceding six years, ML resistance in parasitic nematodes of alpacas on this farm was suspected. FECRT revealed that the efficacy of closantel was 99% (95% CI 93-100), whereas that of ivermectin was 35% (95% CI 0-78), indicating that the treatment failure was likely due to the presence of ML-resistant nematodes. Larval culture of faecal samples collected following ivermectin treatment consisted of 99% H. contortus and 1% Cooperia oncophora, a result confirmed using a PCR assay. CONCLUSIONS: This study provides the first evidence of ML resistance in H. contortus in alpacas in Australia. Based on the extent of anthelmintic resistance in sheep gastrointestinal nematodes in Australia, veterinarians and alpaca owners should be encouraged to implement integrated parasite management strategies to improve nematode control in alpacas

Mosquito Abundance, Bed net Coverage and Other Factors Associated with Variations in Sporozoite Infectivity Rates in Four Villages of Rural Tanzania.

Entomological surveys are of great importance in decision-making processes regarding malaria control strategies because they help to identify associations between vector abundance both species-specific ecology and disease intervention factors associated with malaria transmission. Sporozoite infectivity rates, mosquito host blood meal source, bed net coverage and mosquito abundance were assessed in this study. A longitudinal survey was conducted in four villages in two regions of Tanzania. Malaria vectors were sampled using the CDC light trap and pyrethrum spray catch methods. In each village, ten paired houses were selected for mosquitoes sampling. Sampling was done in fortnight case and study was undertaken for six months in both Kilimanjaro (Northern Tanzania) and Dodoma (Central Tanzania) regions. A total of 6,883 mosquitoes were collected including: 5,628 (81.8%) Anopheles arabiensis, 1,100 (15.9%) Culex quinquefasciatus, 89 (1.4%) Anopheles funestus, and 66 (0.9%) Anopheles gambiae s.s. Of the total mosquitoes collected 3,861 were captured by CDC light trap and 3,022 by the pyrethrum spray catch method. The overall light trap: spray catch ratio was 1.3:1. Mosquito densities per room were 96.5 and 75.5 for light trap and pyrethrum spray catch respectively. Mosquito infectivity rates between villages that have high proportion of bed net owners and those without bed nets was significant (P < 0.001) and there was a significant difference in sporozoite rates between households with and without bed nets in these four villages (P < 0.001). Malaria remains a major problem in the study areas characterized as low transmission sites. Further studies are required to establish the annual entomological inoculation rates and to observe the annual parasitaemia dynamics in these communities. Outdoor mosquitoes collection should also be considered

Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles.

The naked mole-rat Heterocephalus glaber is a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of cardiovascular disease. To identify the mechanisms behind these exceptional traits, metabolomics and RNAseq of cardiac tissue from naked mole-rats was compared to other African mole-rat genera (Cape, Cape dune, Common, Natal, Mahali, Highveld and Damaraland mole-rats) and evolutionarily divergent mammals (Hottentot golden mole and C57/BL6 mouse). We identify metabolic and genetic adaptations unique to naked mole-rats including elevated glycogen, thus enabling glycolytic ATP generation during cardiac ischemia. Elevated normoxic expression of HIF-1α is observed while downstream hypoxia responsive-genes are down-regulated, suggesting adaptation to low oxygen environments. Naked mole-rat hearts show reduced succinate levels during ischemia compared to C57/BL6 mouse and negligible tissue damage following ischemia-reperfusion injury. These evolutionary traits reflect adaptation to a unique hypoxic and eusocial lifestyle that collectively may contribute to their longevity and health span

Primary progressive aphasia: six questions in search of an answer

Here, we review recent progress in the diagnosis and management of primary progressive aphasia—the language-led dementias. We pose six key unanswered questions that challenge current assumptions and highlight the unresolved difficulties that surround these diseases. How many syndromes of primary progressive aphasia are there—and is syndromic diagnosis even useful? Are these truly ‘language-led’ dementias? How can we diagnose (and track) primary progressive aphasia better? Can brain pathology be predicted in these diseases? What is their core pathophysiology? In addition, how can primary progressive aphasia best be treated? We propose that pathophysiological mechanisms linking proteinopathies to phenotypes may help resolve the clinical complexity of primary progressive aphasia, and may suggest novel diagnostic tools and markers and guide the deployment of effective therapies

Interactions between downslope flows and a developing cold-air pool

A numerical model has been used to characterize the development of a region of enhanced cooling in an alpine valley with a width of order (Formula presented.) km, under decoupled stable conditions. The region of enhanced cooling develops largely as a region of relatively dry air which partitions the valley atmosphere dynamics into two volumes, with airflow partially trapped within the valley by a developing elevated inversion. Complex interactions between the region of enhanced cooling and the downslope flows are quantified. The cooling within the region of enhanced cooling and the elevated inversion is almost equally partitioned between radiative and dynamic effects. By the end of the simulation, the different valley atmospheric regions approach a state of thermal equilibrium with one another, though this cannot be said of the valley atmosphere and its external environment.Peer reviewe

The emission by dust and stars of nearby galaxies in the Herschel KINGFISH survey

Using new far-infrared imaging from the Herschel Space Observatory with ancillary data from ultraviolet (UV) to submillimeter wavelengths, we estimate the total emission from dust and stars of 62 nearby galaxies in the KINGFISH survey in a way that is as empirical and model independent as possible. We collect and exploit these data in order to measure from the spectral energy distributions (SEDs) precisely how much stellar radiation is intercepted and re-radiated by dust, and how this quantity varies with galaxy properties. By including SPIRE data, we are more sensitive to emission from cold dust grains than previous analyses at shorter wavelengths, allowing for more accurate estimates of dust temperatures and masses. The dust/stellar flux ratio, which we measure by integrating the SEDs, has a range of nearly three decades (from 10(-2.2) to 10(0.5)). The inclusion of SPIRE data shows that estimates based on data not reaching these far-IR wavelengths are biased low by 17% on average. We find that the dust/stellar flux ratio varies with morphology and total infrared (IR) luminosity, with dwarf galaxies having faint luminosities, spirals having relatively high dust/stellar ratios and IR luminosities, and some early types having low dust/stellar ratios. We also find that dust/stellar flux ratios are related to gas-phase metallicity ((log(f(dust)/f(*)) over bar) = -0.66 +/- 0.08 and -0.22 +/- 0.12 for metal-poor and intermediate-metallicity galaxies, respectively), while the dust/stellar mass ratios are less so (differing by approximate to 0.2 dex); the more metal-rich galaxies span a much wider range of the flux ratios. In addition, the substantial scatter between dust/stellar flux and dust/stellar mass indicates that the former is a poor proxy of the latter. Comparing the dust/stellar flux ratios and dust temperatures, we also show that early types tend to have slightly warmer temperatures (by up to 5 K) than spiral galaxies, which may be due to more intense interstellar radiation fields, or possibly to different dust grain compositions. Finally, we show that early types and early-type spirals have a strong correlation between the dust/stellar flux ratio and specific star formation rate, which suggests that the relatively bright far-IR emission of some of these galaxies is due to ongoing (if limited) star formation as well as to the radiation field from older stars, which is heating the dust grains