Use-case scenarios for an anti-Cryptosporidium therapeutic.

Cryptosporidium is a widely distributed enteric parasite that has an increasingly appreciated pathogenic role, particularly in pediatric diarrhea. While cryptosporidiosis has likely affected humanity for millennia, its recent "emergence" is largely the result of discoveries made through major epidemiologic studies in the past decade. There is no vaccine, and the only approved medicine, nitazoxanide, has been shown to have efficacy limitations in several patient groups known to be at elevated risk of disease. In order to help frontline health workers, policymakers, and other stakeholders translate our current understanding of cryptosporidiosis into actionable guidance to address the disease, we sought to assess salient issues relating to clinical management of cryptosporidiosis drawing from a review of the literature and our own field-based practice. This exercise is meant to help inform health system strategies for improving access to current treatments, to highlight recent achievements and outstanding knowledge and clinical practice gaps, and to help guide research activities for new anti-Cryptosporidium therapies

Home-Based HIIT and Traditional MICT Prescriptions Improve Cardiorespiratory Fitness to a Similar Extent Within an Exercise Referral Scheme for At-Risk Individuals

Exercise referral schemes (ERS) are used to promote physical activity within primary care. Traditionally, ERS are conducted in a gym or leisure-center setting, with exercise prescriptions based on moderate-intensity continuous training (MICT). Home-based high-intensity interval training (Home-HIIT) has the potential to reduce perceived barriers to exercise, including lack of time and access to facilities, compared to traditional MICT prescription used with ERS and improve health related outcomes. We hypothesized that Home-HIIT would mediate greater improvement in cardiorespiratory fitness (CRF) by virtue of greater adherence and compliance to the exercise prescription, compared to MICT. Methods: Patients enrolled on an ERS (Liverpool, United Kingdom) were recruited for a pragmatic trial. Participants self-selected either 12 weeks of MICT (45–135 min/week at 50–70% HRmax or Home-HIIT (4–9 min × 1 min intervals at ≥80% of HRmax, interspersed with 1 min rest). The primary outcome was the change in CRF (VO2peak) at post-intervention (12 weeks) and follow-up (3-month post intervention), using intention-to-treat analysis. Results:154 participants (age 48 ± 10y; BMI 30.5 ± 6.1 kg/m20.05). Adherence to the prescribed programs was similar (MICT 48 ± 35%, Home-HIIT 39 ± 36%, P [ClinicalTrials.gov], identifier [NCT04553614]

Evidence-based vs. social media based high-intensity interval training protocols: Physiological and perceptual responses.

OBJECTIVE: High intensity interval training (HIIT) is a time-efficient exercise modality to improve cardiorespiratory fitness, and has recently been popularised by social media influencers. However, little is known regarding acute physiological and perceptual responses to these online protocols compared to HIIT protocols used within research. The aim was to investigate acute physiological, perceptual and motivational responses to two HIIT protocols popular on social media, and compare these to two evidence-based protocols. METHODS: Twenty-seven recreationally active (>1 exercise session /week) participants (Age: 22±3y, BMI: 24.3±2.4) completed a randomised cross-over study, whereby each participant completed four HIIT protocols, two already established in research (Ergo-60:60 (cycling 10x60s at 100%Wmaxwith 60s rest), BW-60:60 (body-weight exercises 10x60swith 60s rest)) and two promoted on social media (SM-20:10 (body-weight exercises 20x20swith 10s rest) and SM-40:20 (body-weight exercises 15x40s with 20s rest)). Blood lactate, heart rate (HR), feeling scale (FS), felt arousal scale (FSA), enjoyment and perceived competence were measured in response to each protocol. RESULTS: Significant differences were observed between BW-60:60 and SM-20:10 for the proportion of intervals meeting the ACSM high-intensity exercise criterion (>80% of HRmax) (BW-60:60 93±10%, SM-20:10 74±20%, P = 0.039) and change in lactate (BW-60:60 +7.8±3.7mmol/L, SM-20:10 +5.5±2.6mmol/L, P = 0.001). The percentage of time spent above the criterion HR was also significantly lower in SM-20:10 compared to all other protocols (Ergo-60:60 13.9±4.9min, BW-60:60 13.5±3.5min, SM-40:20 12.1±2.4min, SM-20:10 7.7±3.1, P0.05). Enjoyment was higher upon completion of BW-60:60 compared to Ergo-60:60 and SM-40:20 (P<0.05). CONCLUSIONS: This study shows that HIIT protocols available on social media offer an interesting real-world alternative for promoting exercise participation. Future studies should continue to investigate these highly popular and practical HIIT protocols

Divergence exists in the subcellular distribution of intramuscular triglyceride in human skeletal muscle dependent on the choice of lipid dye.

Despite over 50 years of research, a comprehensive understanding of how intramuscular triglyceride (IMTG) is stored in skeletal muscle and its contribution as a fuel during exercise is lacking. Immunohistochemical techniques provide information on IMTG content and lipid droplet (LD) morphology on a fibre type and subcellular-specific basis, and the lipid dye Oil Red O (ORO) is commonly used to achieve this. BODIPY 493/503 (BODIPY) is an alternative lipid dye with lower background staining and narrower emission spectra. Here we provide the first quantitative comparison of BODIPY and ORO for investigating exercise-induced changes in IMTG content and LD morphology on a fibre type and subcellular-specific basis. Estimates of IMTG content were greater when using BODIPY, which was predominantly due to BODIPY detecting a larger number of LDs, compared to ORO. The subcellular distribution of intramuscular lipid was also dependent on the lipid dye used; ORO detects a greater proportion of IMTG in the periphery (5 μm below cell membrane) of the fibre, whereas IMTG content was higher in the central region using BODIPY. In response to 60 min moderate-intensity cycling exercise, IMTG content was reduced in both the peripheral (- 24%) and central region (- 29%) of type I fibres (P < 0.05) using BODIPY, whereas using ORO, IMTG content was only reduced in the peripheral region of type I fibres (- 31%; P < 0.05). As well as highlighting some methodological considerations herein, our investigation demonstrates that important differences exist between BODIPY and ORO for detecting and quantifying IMTG on a fibre type and subcellular-specific basis

Nitrogen and sulphur management: challenges for organic sources in temperate agricultural systems

A current global trend towards intensification or specialization of agricultural enterprises has been accompanied by increasing public awareness of associated environmental consequences. Air and water pollution from losses of nutrients, such as nitrogen (N) and sulphur (S), are a major concern. Governments have initiated extensive regulatory frameworks, including various land use policies, in an attempt to control or reduce the losses. This paper presents an overview of critical input and loss processes affecting N and S for temperate climates, and provides some background to the discussion in subsequent papers evaluating specific farming systems. Management effects on potential gaseous and leaching losses, the lack of synchrony between supply of nutrients and plant demand, and options for optimizing the efficiency of N and S use are reviewed. Integration of inorganic and organic fertilizer inputs and the equitable re-distribution of nutrients from manure are discussed. The paper concludes by highlighting a need for innovative research that is also targeted to practical approaches for reducing N and S losses, and improving the overall synchrony between supply and demand

Applying human factors methods to explore ‘Work as Imagined’ and ‘Work as Done’ in the Emergency Department’s response to chemical, biological, radiological, and nuclear events

The Emergency Department (ED) is a complex, hectic, and high-pressured environment. Chemical, Biological, Radiological, and Nuclear (CBRN) events are multi-faceted emergencies and present numerous challenges to ED staff (first receivers) with large scale trauma, consequently requiring a combination of complex responses. Human Factors and Ergonomics (HF/E) methods such as Hierarchical Task Analysis (HTA) have been used in healthcare research. However, HF/E methods and theory have not been combined to understand how the ED responds to CBRN events. This study aimed to compare Work as Imagined (WAI) and Work as Done (WAD) in the ED CBRN response in a UK based hospital. WAI was established by carrying out document analyses on a CBRN plan and WAD by exploring first receivers response to CBRN scenario cards. The responses were converted to HTAs and compared. The WAI HTAs showed 4-8 phases of general organizational responsibilities during a CBRN event. WAD HTAs placed emphasis on diagnosing and treating presenting conditions. A comparison of WAI and WAD HTAs highlighted common actions and tasks. This study has identified three key differences between WAI and WAD in the ED CBRN response: 1) documentation of the CBRN event 2) treating the patient and 3) diagnosing the presenting complaint. Findings from this study provide an evidence base which can be used to inform future clinical policy and practice in providing safe and high quality care during CBRN events in the ED

Reliability of Protein Abundance and Synthesis Measurements in Human Skeletal Muscle.

We investigated the repeatability of dynamic proteome profiling (DPP), which is a novel technique for measuring the relative abundance (ABD) and fractional synthesis rate (FSR) of proteins in humans. LC-MS analysis was performed on muscle samples taken from male participants (n = 4) that consumed 4 × 50 ml doses of deuterium oxide (2 H2 O) per day for 14 d. ABD was measured by label-free quantitation and FSR was calculated from time-dependent changes in peptide mass isotopomer abundances. One-hundred and one proteins had at least 1 unique peptide and were used in the assessment of protein ABD. Fifty-four of these proteins met more stringent criteria and were used in the assessment of FSR data. The median (M), lower- (Q1 ) and upper-quartile (Q3 ) values for protein FSR (%/d) were M = 1.63, Q1  = 1.07, Q3  = 3.24. The technical CV of ABD data had a median value of 3.6% (Q1 1.7% - Q3 6.7%), whereas the median CV of FSR data was 10.1% (Q1 3.5% - Q3 16.5%). These values compare favorably against other assessments of technical repeatability of proteomics data, which often set a CV of 20% as the upper bound of acceptability. This article is protected by copyright. All rights reserved

Binary orbits as the driver of γ-ray emission and mass ejection in classical novae

Classical novae are the most common astrophysical thermonuclear explosions, occurring on the surfaces of white dwarf stars accreting gas from companions in binary star systems. Novae typically expel �10,000 solar masses of material at velocities exceeding 1,000 km/s. However, the mechanism of mass ejection in novae is poorly understood, and could be dominated by the impulsive flash of the thermonuclear runaway, prolonged optically thick winds, or binary interaction with the nova envelope. Classical novae are now routinely detected in GeV gamma-rays, suggesting that relativistic particles are accelerated by strong shocks in nova ejecta. Here we present high-resolution imaging of the gamma-ray-emitting nova V959 Mon at radio wavelengths, showing that its ejecta were shaped by binary motion: some gas was expelled rapidly along the poles as a wind from the white dwarf, while denser material drifted out along the equatorial plane, propelled by orbital motion. At the interface between the equatorial and polar regions, we observe synchrotron emission indicative of shocks and relativistic particle acceleration, thereby pinpointing the location of gamma-ray production. Binary shaping of the nova ejecta and associated internal shocks are expected to be widespread among novae, explaining why many novae are gamma-ray emitters

Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe

Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery1,2, spreading efficiently via low-dose fecal-oral transmission3,4. Historically, S. sonnei has been predominantly responsible for dysentery in developed countries, but is now emerging as a problem in the developing world, apparently replacing the more diverse S. flexneri in areas undergoing economic development and improvements in water quality4-6. Classical approaches have shown S. sonnei is genetically conserved and clonal7. We report here whole-genome sequencing of 132 globally-distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and has diversified into several distinct lineages with unique characteristics. Our analysis suggests the majority of this diversification occurred in Europe, followed by more recent establishment of local pathogen populations in other continents predominantly due to the pandemic spread of a single, rapidly-evolving, multidrug resistant lineage