KAI407, a potent non-8-aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro.

Preventing relapses of Plasmodium vivax malaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. For future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. A new compound with potential radical cure activity was identified using a low-throughput assay of in vitro-cultured hypnozoite forms of Plasmodium cynomolgi (an excellent and accessible model for Plasmodium vivax). In this assay, primary rhesus hepatocytes are infected with P. cynomolgi sporozoites, and exoerythrocytic development is monitored in the presence of compounds. Liver stage cultures are fixed after 6 days and stained with anti-Hsp70 antibodies, and the relative proportions of small (hypnozoite) and large (schizont) forms relative to the untreated controls are determined. This assay was used to screen a series of 18 known antimalarials and 14 new non-8-aminoquinolines (preselected for blood and/or liver stage activity) in three-point 10-fold dilutions (0.1, 1, and 10 μM final concentrations). A novel compound, designated KAI407 showed an activity profile similar to that of primaquine (PQ), efficiently killing the earliest stages of the parasites that become either primary hepatic schizonts or hypnozoites (50% inhibitory concentration [IC50] for hypnozoites, KAI407, 0.69 μM, and PQ, 0.84 μM; for developing liver stages, KAI407, 0.64 μM, and PQ, 0.37 μM). When given as causal prophylaxis, a single oral dose of 100 mg/kg of body weight prevented blood stage parasitemia in mice. From these results, we conclude that KAI407 may represent a new compound class for P. vivax malaria prophylaxis and potentially a radical cure

PB1-F2 Proteins from H5N1 and 20th Century Pandemic Influenza Viruses Cause Immunopathology

With the recent emergence of a novel pandemic strain, there is presently intense interest in understanding the molecular signatures of virulence of influenza viruses. PB1-F2 proteins from epidemiologically important influenza A virus strains were studied to determine their function and contribution to virulence. Using 27-mer peptides derived from the C-terminal sequence of PB1-F2 and chimeric viruses engineered on a common background, we demonstrated that induction of cell death through PB1-F2 is dependent upon BAK/BAX mediated cytochrome c release from mitochondria. This function was specific for the PB1-F2 protein of A/Puerto Rico/8/34 and was not seen using PB1-F2 peptides derived from past pandemic strains. However, PB1-F2 proteins from the three pandemic strains of the 20th century and a highly pathogenic strain of the H5N1 subtype were shown to enhance the lung inflammatory response resulting in increased pathology. Recently circulating seasonal influenza A strains were not capable of this pro-inflammatory function, having lost the PB1-F2 protein's immunostimulatory activity through truncation or mutation during adaptation in humans. These data suggest that the PB1-F2 protein contributes to the virulence of pandemic strains when the PB1 gene segment is recently derived from the avian reservoir

Online versus in-person comparison of Microscale Audit of Pedestrian Streetscapes (MAPS) assessments: reliability of alternate methods

Abstract Background An online version of the Microscale Audit of Pedestrian Streetscapes (Abbreviated) tool was adapted to virtually audit built environment features supportive of physical activity. The current study assessed inter-rater reliability of MAPS Online between in-person raters and online raters unfamiliar with the regions. Methods In-person and online audits were conducted for a total of 120 quarter-mile routes (60 per site) in Phoenix, AZ and San Diego, CA. Routes in each city included 40 residential origins stratified by walkability and SES, and 20 commercial centers. In-person audits were conducted by raters residing in their region. Online audits were conducted by raters in the alternate location using Google Maps (Aerial and Street View) images. The MAPS Abbreviated Online tool consisted of four sections: overall route, street segments, crossings and cul-de-sacs. Items within each section were grouped into subscales, and inter-rater reliability (ICCs) was assessed for subscales at multiple levels of aggregation. Results Online and in-person audits showed excellent agreement for overall positive microscale (ICC = 0.86, 95% CI [0.80, 0.90]) and grand scores (ICC = 0.93, 95% CI [0.89, 0.95]). Substantial to near-perfect agreement was found for 21 of 30 (70%) subscales, valence, and subsection scores, with ICCs ranging from 0.62, 95% CI [0.50, 0.72] to 0.95, 95% CI [0.93, 0.97]. Lowest agreement was found for the aesthetics and social characteristics scores, with ICCs ranging from 0.07, 95% CI [−0.12, 0.24] to 0.27, 95% CI [0.10, 0.43]. Conclusions Results support use of the MAPS Abbreviated Online tool to reliably assess microscale neighborhood features that support physical activity and may be used by raters residing in different geographic regions and unfamiliar with the audit areas

The use of mobile apps and SMS messaging as physical and mental health interventions: systematic review

Background: The initial introduction of the World Wide Web in 1990 brought around the biggest change in information acquisition. Due to the abundance of devices and ease of access they subsequently allow, the utility of mobile health (mHealth) has never been more endemic. A substantial amount of interactive and psychoeducational apps are readily available to download concerning a wide range of health issues. mHealth has the potential to reduce waiting times for appointments; eradicate the need to meet in person with a clinician, successively diminishing the workload of mental health professionals; be more cost effective to practices; and encourage self-care tactics. Previous research has given valid evidence with empirical studies proving the effectiveness of physical and mental health interventions using mobile apps. Alongside apps, there is evidence to show that receiving short message service (SMS) messages, which entail psychoeducation, medication reminders, and links to useful informative Web pages can also be advantageous to a patient’s mental and physical well-being. Available mHealth apps and SMS services and their ever improving quality necessitates a systematic review in the area in reference to reduction of symptomology, adherence to intervention, and usability. Objective: The aim of this review was to study the efficacy, usability, and feasibility of mobile apps and SMS messages as mHealth interventions for self-guided care. Methods: A systematic literature search was carried out in JMIR, PubMed, PsychINFO, PsychARTICLES, Google Scholar, MEDLINE, and SAGE. The search spanned from January 2008 to January 2017. The primary outcome measures consisted of weight management, (pregnancy) smoking cessation, medication adherence, depression, anxiety and stress. Where possible, adherence, feasibility, and usability outcomes of the apps or SMS services were evaluated. Between-group and within-group effect sizes (Cohen d) for the mHealth intervention method group were determined. Results: A total of 27 studies, inclusive of 4658 participants were reviewed. The papers included randomized controlled trials (RCTs) (n=19), within-group studies (n=7), and 1 within-group study with qualitative aspect. Studies show improvement in physical health and significant reductions of anxiety, stress, and depression. Within-group and between-group effect sizes ranged from 0.05-3.37 (immediately posttest), 0.05-3.25 (1-month follow-up), 0.08-3.08 (2-month follow-up), 0.00-3.10 (3-month follow-up), and 0.02-0.27 (6-month follow-up). Usability and feasibility of mHealth interventions, where reported, also gave promising, significant results. Conclusions: The review shows the promising and emerging efficacy of using mobile apps and SMS text messaging as mHealth interventions