Immunization with an mRNA DTP vaccine protects against pertussis in rats.

Bordetella pertussis is a Gram-negative bacterium that is the causative agent of the respiratory disease known as pertussis. Since the switch to the acellular vaccines of DTaP and Tap, pertussis cases in the US have risen and cyclically fallen. We have observed that mRNA pertussis vaccines are immunogenic and protective in mice. Here, we further evaluated the pertussis toxoid mRNA antigen and refined the formulation based on optimal pertussis toxin neutralization in vivo. We next evaluated the mRNA pertussis vaccine in Sprague-Dawley rats using an aerosol B. pertussis challenge model paired with whole-body plethysmography to monitor coughing and respiratory function. Female Sprague-Dawley rats were primed and boosted with either commercially available vaccines (DTaP or wP-DTP), an mRNA-DTP vaccine, or mock-vaccinated. The mRNA-DTP vaccine was immunogenic in rats and induced antigen-specific IgG antibodies comparable to DTaP. Rats were then aerosol challenged with a streptomycin-resistant emerging clinical isolate D420Sm1. Bacterial burden was assessed at days 1 and 9 post-challenge, and the mRNA vaccine reduced burden equal to both DTaP and wP-DTP. Whole-body plethysmography revealed that mRNA-DTP vaccinated rats were well protected against coughing which was comparable to the non-challenged group. These data suggest that an mRNA-DTP vaccine is immunogenic in rats and provides protection against aerosolized B. pertussis challenge in Sprague-Dawley rats.

Early Australian experience in the maintenance of schizophrenia management with 3-monthly paliperidone palmitate.

OBJECTIVES:: Real-world experience from a 6-month product familiarization programme (PFP) for 3-monthly paliperidone palmitate in schizophrenia maintenance treatment. METHODS:: Prescribers completed an online questionnaire for each patient at enrolment with further questions at second dose (re-supply) stage and a second survey of their overall experience at the end. RESULTS:: Ninety-four patients were enrolled and received a first dose and 23 received a second dose within the 6-month programme; 51.1% had been hospitalised for symptom relapse in the previous 2 years. Reasons for prescribing were convenience of 3-monthly dosing for patients (94.7%) and patient choice (54.6%). Prescribers followed-up at least once-monthly (69.6% cases) and indicated in 48.9% they would consider shared GP care. All patients were satisfied with symptom control and either maintained functioning or showed improvement. Clinicians felt confident with administration and identifying suitable patients and were all 'satisfied' or 'somewhat satisfied' with efficacy and tolerability. All felt patients' treatment goals were either 'met' (81.3%) or 'partly met' (18.7%) and none reported dissatisfaction with relapse prevention. CONCLUSIONS:: Convenient 3-monthly dosing was preferred by clinicians and patients, and symptoms were adequately managed. This has the potential to improve adherence and lead to better outcomes as patients only need four intramuscular doses per year.

Multi-channel absolute distance measurement system with sub ppm-accuracy and 20 m range using frequency scanning interferometry and gas absorption cells.

We present an implementation of an absolute distance measurement system which uses frequency scanning interferometry (FSI). The technique, referred to as dynamic FSI, uses two frequency scanning lasers, a gas absorption cell and a reference interferometer to determine the unknown optical path length difference (OPD) of one or many measurement interferometers. The gas absorption cell is the length reference for the measurement system and is traceable to international standards through knowledge of the frequencies of its absorption features. The OPD of the measurement interferometers can vary during the measurement and the variation is measured at the sampling rate of the system (2.77 MHz in the system described here). The system is shown to measure distances from 0.2 m to 20 m with a combined relative uncertainty of 0.41 × 10⁻6 at the two sigma level (k = 2). It will be shown that within a scan the change in OPD of the measurement interferometer can be determined to a resolution of 40 nm.

Precision of frequency scanning interferometry distance measurements in the presence of noise.

A lower limit-the Cramér-Rao bound-on the variance of frequency scanning interferometry (FSI) distance measurements in the presence of noise is presented. We show that, with a suitable analysis method, the variance of experimental measurements almost reaches this limit. In particular, the variance of results with a simple analysis method was 1.54 times the limit over a range of signal-to-noise ratios. This bound aids the understanding of FSI distance measurement uncertainty, and provides a benchmark against which to compare FSI analysis algorithms.

Dehydration Alters Transcript Levels in the Mosquito Midgut, Likely Facilitating Rapid Rehydration following a Bloodmeal.

The mosquito midgut is an important site for bloodmeal regulation while also acting as a primary site for pathogen exposure within the mosquito. Recent studies show that exposure to dehydrating conditions alters mosquito bloodfeeding behaviors as well as post-feeding regulation, likely altering how pathogens interact with the mosquito. Unfortunately, few studies have explored the underlying dynamics between dehydration and bloodmeal utilization, and the overall impact on disease transmission dynamics remains veiled. In this study, we find that dehydration-based feeding in the yellow fever mosquito, Aedes aegypti, prompts alterations to midgut gene expression, as well as subsequent physiological factors involving water control and post-bloodfeeding (pbf) regulation. Altered expression of ion transporter genes and aquaporin 2 (AQP2) in the midgut of dehydrated mosquitoes as well as the rapid reequilibration of hemolymph osmolality after a bloodmeal indicate an ability to expedite fluid and ion processing. These alterations ultimately indicate that female A. aegypti employ mechanisms to ameliorate the detriments of dehydration by imbibing a bloodmeal, providing an effective avenue for rehydration. Continued research into bloodmeal utilization and the resulting effects on arthropod-borne transmission dynamics becomes increasingly important as drought prevalence is increased by climate change.

Intranasal challenge with B. pertussis leads to more severe disease manifestations in mice than aerosol challenge.

The murine Bordetella pertussis challenge model has been utilized in preclinical research for decades. Currently, inconsistent methodologies are employed by researchers across the globe, making it difficult to compare findings. The objective of this work was to utilize the CD-1 mouse model with two routes of challenge, intranasal and aerosol administration of B. pertussis, to understand the differences in disease manifestation elicited via each route. We observed that both routes of B. pertussis challenge result in dose-dependent colonization of the respiratory tract, but overall, intranasal challenge led to higher bacterial burden in the nasal lavage, trachea, and lung. Furthermore, high dose intranasal challenge results in induction of leukocytosis and pro-inflammatory cytokine responses compared to aerosol challenge. These data highlight crucial differences in B. pertussis challenge routes that should be considered during experimental design.

Bloodmeal regulation in mosquitoes curtails dehydration-induced mortality, altering vectorial capacity.

Mosquitoes readily lose water when exposed to any humidity less than that of near saturated air unless mitigated, leading to shifts in behavior, survival, distribution, and reproduction. In this study, we conducted a series of physiological experiments on two prominent species in the Culicinae subfamily: Culex pipiens, a vector of West Nile virus, and Aedes aegypti, a vector of yellow fever and Zika to examine the effects of dehydration. We exposed C. pipiens and A. aegypti to non-dehydrating conditions (saturated air), dehydrating conditions (air at a 0.89 kPa saturation vapor pressure deficit), several recovery conditions, as well as to bloodfeeding opportunities. We show that dehydrated mosquitoes increase bloodfeeding propensity, improve retention, and decrease excretion of a post-dehydration bloodmeal. In addition, mosquitoes that take a bloodmeal prior to dehydration exposure show increased survival over non-bloodfed counterparts. Dehydration-induced alterations in survival, reproduction, and bloodfeeding propensity of C. pipiens and A. aegypti resulted in marked changes to vectorial capacity. Ultimately, these results become increasingly important as drought intensifies in association with climate change and mosquitoes become more likely to experience arid periods.

Recommendations for the optimal care of patients with recent-onset psychosis in the Asia-Pacific region.

Providing optimal care to patients with recent-onset psychosis can improve outcomes and reduce relapse. However, there is a lack of consistency of the implementation of guidelines for such patients across the Asia-Pacific region. We determined a pragmatic set of recommendations for use on a day-to-day basis to help provide optimal care at this crucial stage of illness. The recommendations were developed over a series of meetings by an international faculty of 15 experts from the Asia-Pacific region, Europe, and South Africa. A structured search of the PubMed database was conducted. This was further developed based on the faculty's clinical experience and knowledge of the literature into 10 key aspects of optimal care for patients during the first five years of a diagnosis of a psychotic disorder, with particular relevance to the Asia-Pacific region. Several common principles emerged: adherence to antipsychotic medications is crucial; substance abuse, psychiatric and medical comorbidities should be addressed; psychosocial interventions play a pivotal role; and family members can play a vital role in overall patient care. By following these recommendations, clinicians may improve outcomes for patients with recent-onset psychosis.

Akathisia treated with olanzapine: Three case reports.

There have been reports of clozapine being used in the treatment of neuroleptic-induced akathisia. However, due to clozapine's side effects, its use has been limited. Olazapine has been shown to have a similar receptor occupancy to that of clozapine and also a similar chemical structure. We present three case histories where the commencement of olanzapine has had a dramatic improvement of in the symptoms of akathisia induced by other neuroleptics.