Immune interactions and heterogeneity in transmission drives the pathogen-mediated invasion of grey squirrels in the UK.

Mathematical models highlighted the importance of pathogen-mediated invasion, with the replacement of red squirrels by squirrelpox virus (SQPV) carrying grey squirrels in the UK, a well-known example. In this study, we combine new epidemiological models, with a range of infection characteristics, with recent longitudinal field and experimental studies on the SQPV dynamics in red and grey squirrel populations to better infer the mechanistic basis of the disease interaction. A key finding is that a model with either partial immunity or waning immunity and reinfection, where individuals become seropositive on the second exposure to infection, that up to now has been shown in experimental data only, can capture the key aspects of the field study observations. By fitting to SQPV epidemic observations in isolated red squirrel populations, we can infer that SQPV transmission between red squirrels is significantly (4×) higher than the transmission between grey squirrels and as a result our model shows that disease-mediated replacement of red squirrels by greys is considerably more rapid than replacement in the absence of SQPV. Our findings recover the key results of the previous model studies, which highlights the value of simple strategic models that are appropriate when there are limited data, but also emphasise the likely complexity of immune interactions in wildlife disease and how models can help infer disease processes from field data.

Performance of dairy cows offered silages produced from grass swards harvested on either three or five occasions during the growing season.

The nutritive value of grass silage can be improved by harvesting herbage at a less mature growth stage, which in practice usually involves more frequent harvests. This study examined the performance of dairy cows offered grass silages produced from perennial ryegrass (Lolium perenne) based swards harvested at 2 different frequencies during the growing season (3-harvest (3H) vs. 5-harvest (5H)). Thirty-four mid-lactation (av. 147 d in milk) dairy cows (30 multiparous, 4 primiparous) were offered either 3H or 5H silages in a continuous design (21 wk) experiment. Within each treatment cows were offered silage from each harvest (in harvest number order) for a pre-determined number of days in proportion to herbage DM yield at each harvest. Silages were offered ad libitum while a common concentrate was offered to all cows at 12.0 kg per cow/d over the first 15 wk of the study, 8.0 kg per cow/d during wk 16 -19 and 6.0 kg cow/d during wk 20 - 21. Total yield of herbage harvested over the season from within 3H and 5H were 12.6 and 11.2 t DM/ha, respectively. Across all harvests the mean ME and CP concentration of silages were 10.9 MJ/kg DM and 131 g/kg DM for 3H, and 11.5 MJ/kg DM and 152 g/kg DM for 5H. Silage DMI was greater for cows offered 5H silages compared with 3H silages (14.1 vs. 11.7 kg/d, respectively). Cows offered 5H silages had a greater daily milk yield (33.5 vs. 31.9 kg) and ECM yield (37.4 vs. 35.6 kg) compared with cows offered 3H silages. Treatment had no effect on milk fat or protein concentration. Cows offered 5H silages produced milk with greater concentrations of CLA and n-3 fatty acids. Treatment had no effect on mean BW or BCS, or on efficiency metrics such as milk yield or ECM yield per kg of DMI. Molar proportions of VFA in ruminal fluid differed between the treatments, with cows offered 3H silages having higher proportion of total butyrate (15.9 vs. 14.4% of total VFA) and lower total valerate (3.2 vs. 3.7% of total VFA) compared with those offered 5H. The acetate: propionate and acetate plus butyrate: propionate ratios were unaffected by treatment. In conclusion, increasing herbage harvesting frequency from 3 to 5 times per year improved the nutritional value of the resulting silages, and this led to higher silage DMI, milk yield and ECM yield. However, overall production efficiency (ECM/DMI) was unaffected by treatment.

Bioavailability of vitamin D biofortified pork meat: results of an acute human crossover study in healthy adults.

Vitamin D intakes are concerningly low. Food-based strategies are urgently warranted to increase vitamin D intakes and subsequently improve 25-hydroxyvitamin D (25(OH)D) concentrations. This acute randomised three-way crossover study investigated the efficacy of vitamin D biofortified pork derived from pigs exposed to UVB light to increase serum 25(OH)D3 concentrations, compared to a dose-matched vitamin D3 supplement and control pork in adults (n = 14). Blood samples were obtained at baseline and then 1.5, 3, 6, 9 and 24 h postprandially. There was a significant effect of time (p < 0.01) and a significant treatment*time interaction (p < 0.05). UV pork and supplement significantly increased within-group serum 25(OH)D3 concentrations over timepoints (p < 0.05) (max. change 0.9 nmol/L (2.2%) UV pork, 1.5 nmol/L (3.5%) supplement, 0.7 nmol/L (1.9%) control). Vitamin D biofortified pork modestly increased 25(OH)D3 concentrations and produced a similar response pattern as a dose-matched vitamin D supplement, but biofortification protocols should be further optimised to ensure differentiation from standard pork.

RNA-Based Therapy for Cryptosporidium parvum Infection: Proof-of-Concept Studies.

Cryptosporidium is a leading cause of moderate-to-severe diarrhea in children, which is one of the major causes of death in children under 5 years old. Nitazoxanide is the only FDA-approved treatment for cryptosporidiosis. However, it has limited efficacy in immunosuppressed patients and malnourished children. Therefore, it is urgent to develop novel therapies against this parasite. RNA interference-mediated therapies are emerging as novel approaches for the treatment of infectious diseases. We have developed a novel method to silence essential genes in Cryptosporidium using single-stranded RNA (ssRNA)/Argonaute (Ago) complexes. In this work we conducted proof-of-concept studies to test the anticryptosporidial activity of these complexes by silencing Cryptosporidium parvum nucleoside diphosphate kinase (NDK) using in vitro and in vivo models. We demonstrated that a 3-day treatment with anti-sense NDK ssRNA/Ago decreased parasite burden by ~98% on infected cells. In vivo studies showed that ssRNA/Ago complexes encapsulated in lipid nanoparticles can be delivered onto intestinal epithelial cells of mice treated orally. In addition a cryptosporidiosis-mouse model showed that treatment with NDK ssRNA/Ago complexes reduced oocyst shedding in 4/5 SCID/beige mice during the acute phase of the infection. Our findings highlight the potential use of antisense RNA-based therapy as an alternative approach to cryptosporidiosis treatment.

Neurocysticercosis: an update on diagnosis, treatment, and prevention.

Neurocysticercosis (NCC) is an important cause of neurological disease worldwide, including imported cases in nonendemic countries. PURPOSE OF REVIEW: The purpose of this review is to update information on diagnosis, management, and prevention of neurocysticercosis. RECENT FINDINGS: WHO and Infectious Diseases Society of America/American Society of Tropical Medicine and Hygiene guidelines emphasize the importance of corticosteroids and antiparasitic drugs for viable parenchymal disease and single enhancing lesions. Subarachnoid NCC is associated with a high fatality rate unless optimally treated. Advances in subarachnoid NCC include use of prolonged antiparasitic and anti-inflammatory courses and the increasing use of antigen-detection and quantitative PCR assays in diagnosis and follow-up. Emerging data support the safety and efficacy of minimally invasive surgery in ventricular cases. Calcified neurocysticercosis continues to be associated with a high burden of disease. Field studies are demonstrating the feasibility of eradication using a combination of mass chemotherapy for human tapeworms and vaccination/treatment of porcine cysticercosis. SUMMARY: NCC remains an important and challenging cause of neurological disease with significant morbidity despite advances in treatment and prevention.

Bacillus Calmette-Guerin (BCG) induces superior anti-tumour responses by Vδ2+ T cells compared with the aminobisphosphonate drug zoledronic acid.

Vδ2+ T cells can recognize malignantly transformed cells as well as those infected with mycobacteria. This cross-reactivity supports the idea of using mycobacteria to manipulate Vδ2+ T cells in cancer immunotherapy. To date, therapeutic interventions using Vδ2+ T cells in cancer have involved expanding these cells in or ex vivo using zoledronic acid (ZA). Here, we show that the mycobacterium Bacillus Calmette-Guérin (BCG) also causes Vδ2+ T-cell expansion in vitro and that resulting Vδ2+ cell populations are cytotoxic toward tumour cell lines. We show that both ZA and BCG-expanded Vδ2+ cells effectively killed both Daudi and THP-1 cells. THP-1 cell killing by both ZA and BCG-expanded Vδ2+ cells was enhanced by treatment of targets cells with ZA. Although no difference in cytotoxic activity between ZA- and BCG-expanded Vδ2+ cells was observed, BCG-expanded cells degranulated more and produced a more diverse range of cytokines upon tumour cell recognition compared to ZA-expanded cells. ZA-expanded Vδ2+ cells were shown to upregulate exhaustion marker CD57 to a greater extent than BCG-expanded Vδ2+ cells. Furthermore, ZA expansion was associated with upregulation of inhibitory markers PD-1 and TIM3 in a dose-dependent manner whereas PD-1 expression was not increased following expansion using BCG. Intradermal BCG vaccination of rhesus macaques caused in vivo expansion of Vδ2+ cells. In combination with the aforementioned in vitro data, this finding suggests that BCG treatment could induce expansion of Vδ2+ T cells with enhanced anti-tumour potential compared to ZA treatment and that either ZA or BCG could be used intratumourally as a means to potentiate stronger anti-tumour Vδ2+ T-cell responses.

Dissemination and implementation strategies for physical activity guidelines among adults with disability, chronic conditions, and pregnancy: a systematic scoping review.

BACKGROUND: Physical activity guidelines for adults with disability, chronic conditions, and pregnancy (i.e., specific populations) have been developed to provide guidance for engaging in physical activity. However, specific populations remain considerably less physically active compared to the general population, presenting a knowledge-practice gap. PURPOSE: The purpose of this systematic scoping review was to identify and evaluate strategies for disseminating and implementing physical activity guidelines among specific populations and/or stakeholders (e.g., healthcare professionals) in Canada. METHODS: Five search approaches (peer-reviewed literature databases, grey literature database, custom Google search engines, targeted web-based searches, and content expert consultation) identified records documenting and/or evaluating strategies that had been used to disseminate or implement guidelines from a predetermined list. Systematic and scoping review protocols were followed. Risk of bias assessments were conducted for all studies that evaluated strategies. RESULTS: Eighty-one records reported dissemination strategies (n = 42), implementation strategies (n = 28), or both (n = 11). Twenty-two studies reporting on 29 evaluated strategies were deemed "serious" or "high" risk of bias. Common guideline dissemination and implementation strategies are deliberated and recommendations for future practice are made. CONCLUSIONS: Findings may inform future dissemination and implementation efforts for physical activity guidelines in Canada or similar countries.

Fecal stanols show simultaneous flooding and seasonal precipitation change correlate with Cahokia's population decline.

A number of competing hypotheses, including hydroclimatic variations, environmental degradation and disturbance, and sociopolitical disintegration, have emerged to explain the dissolution of Cahokia, the largest prehistoric population center in the United States. Because it is likely that Cahokia's decline was precipitated by multiple factors, some environmental and some societal, a robust understanding of this phenomenon will require multiple lines of evidence along with a refined chronology. Here, we use fecal stanol data from Horseshoe Lake, Illinois, as a population proxy for Cahokia and the broader Horseshoe Lake watershed. We directly compare the fecal stanol data with oxygen stable-isotope and paleoenvironmental data from the same sediment cores to evaluate the role of flooding, drought, and environmental degradation in Cahokia's demographic decline and sociopolitical reorganization. We find that Mississippi River flooding and warm season droughts detrimental to agriculture occurred circa (ca.) 1150 CE and possibly generated significant stress for Cahokia's inhabitants. Our findings implicate climate change during the Medieval Climatic Anomaly to Little Ice Age transition as an important component of population and sociopolitical transformations at Cahokia, and demonstrate how climate transitions can simultaneously influence multiple environmental processes to produce significant challenges to society.

Triclabendazole Treatment Failure for Fasciola hepatica Infection among Preschool and School-Age Children, Cusco, Peru1.

We conducted a retrospective cohort study of children who had chronic fascioliasis in the highlands of Peru to determine triclabendazole treatment efficacy. Children passing Fasciola eggs in stool were offered directly observed triclabendazole treatment (>1 doses of 10 mg/kg). Parasitologic cure was evaluated by using microscopy of stool 1-4 months after each treatment. A total of 146 children who had chronic fascioliasis participated in the study; 53% were female, and the mean ± SD age was 10.4 ± 3.1 years. After the first treatment, 55% of the children achieved parasitologic cure. Cure rates decreased after the second (38%), third (30%), and fourth (23%) treatments; 17 children (11.6%) did not achieve cure after 4 treatments. Higher baseline egg counts and lower socioeconomic status were associated with triclabendazole treatment failure. Decreased triclabendazole efficacy in disease-endemic communities threatens control efforts. Further research on triclabendazole resistance and new drugs to overcome it are urgently needed.

Plasma cytokines during acute human fascioliasis.

Fascioliasis is a foodborne trematode endemic worldwide. Children under 15 years have the highest prevalence of infection. We hypothesized that acute fascioliasis would be associated with more pronounced cytokine changes than in chronic disease or no helminth infections. To test this hypothesis, 33 children who lived in the Peruvian highlands were classified into 3 groups: acute fascioliasis, chronic fascioliasis, and no helminth infection. Type Th1, Th2, and Th17 cytokines were measured in plasma by cytometric bead array. Children with acute infection had higher levels of IL-5 and IL-17 compared with controls (p < 0.001 and p < 0.007, respectively). The increased IL-5 plasma concentration in children with acute infection was associated with the eosinophilia found in that group.

Perceived usefulness and ease of use of fundoscopy by medical students: a randomised crossover trial of six technologies (eFOCUS 1).

BACKGROUND: Fundoscopy outside ophthalmology is in decline, and the technical demands of the traditional direct ophthalmoscope examination are likely contributing. Alternative fundoscopy technologies are increasingly available, yet valid comparisons between fundoscopy technologies are lacking. We aimed to assess medical students' perceptions of usefulness and ease of use of traditional and contemporary fundus-viewing technologies including smartphone fundoscopy. METHODS: One hundred forty-six second-year medical students participated in a cross-sectional, randomised, cross-over study of fundoscopy methods. Medical students completed small group training sessions using six current fundoscopy technologies including: a non-mydriatic fundus camera; two types of direct fundoscopy; and three types of smartphone fundoscopy. A novel survey of perceived usefulness and ease of use was then completed by students. RESULTS: Repeated-measures ANOVA found students rated both the perceived usefulness (p< 0.001) and ease of use (p< 0.001) of smartphone fundoscopy significantly higher than both the non-mydriatic camera and direct fundoscopy. CONCLUSIONS: Smartphone fundoscopy was found to be significantly more useful and easier to use than other modalities. Educators should optimise student access to novel fundoscopy technologies such as smartphone fundoscopy which may mitigate the technical challenges of fundoscopy and reinvigorate use of this valuable clinical examination.

The ALERT model of care for the assessment and personalized management of patients with lymphoedema.

BACKGROUND: This study documents the development and evaluation of a comprehensive multidisciplinary model for the assessment and personalized care of patients with lymphoedema. METHODS: The Australian Lymphoedema Education Research and Treatment (ALERT) programme originated as an advanced clinic for patients considering surgery for lymphoedema. The programme commenced liposuction surgery in May 2012 and then introduced lymph node transfer in 2013 and lymphovenous anastomosis (LVA) in 2016. An outpatient conservative treatment clinic was established in 2016. ALERT commenced investigations with indocyanine green (ICG) lymphography in late 2015, leading to the creation of a diagnostic assessment clinic offering ICG in 2017. RESULTS: Since 2012, 1200 new patients have been referred to ALERT for assessment of lymphoedema for a total of 5043 episodes of care. The introduction of ICG lymphography in 2015 initially allowed better screening for LVA, but is now used not only to guide surgical options, but also as a diagnostic tool and to guide manual lymphatic drainage massage. The total number of new patients who attended the surgical assessment clinic to December 2018 was 477, with 162 patients (34·0 per cent) undergoing surgery. CONCLUSION: The ALERT programme has developed a multidisciplinary model of care for personalized lymphoedema treatment options based on clinical, imaging and ICG lymphography. Patients are selected for surgery based on several individual factors.

ANTECEDENTES: Este estudio presenta el desarrollo y valoración de un modelo multidisciplinario integral para la evaluación y atención personalizada de pacientes con linfedema. MÉTODOS: El programa australiano de educación en investigación y tratamiento del linfedema (Australian Lymphoedema Education Research and Treatment, ALERT) se originó como un centro clínico avanzado para pacientes que consideran la cirugía como tratamiento para el linfedema. El programa se inició en mayo del 2012 con la cirugía de liposucción, introduciendo la cirugía de transferencia ganglionar (lymph node transfer, LNT) en 2013 y la anastomosis linfovenosa (lymphovenous anastomosis, LVA) en 2016. En 2016 se estableció una clínica de tratamiento conservador ambulatorio. ALERT comenzó las investigaciones con la linfografía con verde de indocianina (indocyanine green, ICG) a fines del 2015, lo que se siguió de la creación de una clínica de evaluación diagnóstica que ofrece ICG en 2017. RESULTADOS: Desde el 2012, 1.200 pacientes nuevos han sido referidos a ALERT para la evaluación de un linfedema, con un total de 5.043 episodios atendidos. La introducción inicialmente de linfografía con ICG en 2015 permitió un mejor cribaje para LVA, pero actualmente se utiliza no solo como guía de las opciones quirúrgicas, sino también como herramienta diagnóstica y como guía del masaje de drenaje linfático manual (manual lymphatic drainage, MLD). El número total de pacientes nuevos atendidos en la clínica de evaluación quirúrgica hasta diciembre de 2018 fue de 477, con 122 pacientes (34%) tratados quirúrgicamente. El modelo tal como se ha descrito, ha atraído a pacientes de toda Australia y Nueva Zelanda. CONCLUSIÓN: El programa ALERT ha desarrollado un modelo multidisciplinario de atención para las opciones de tratamiento personalizado del linfedema basado en la evaluación clínica, por imagen (MRI y LSG) y linfografía con ICG. Los pacientes se seleccionan cuidadosamente para el tratamiento quirúrgico en función de varios factores relacionados con el paciente, el tumor, los linfáticos y las opciones terapéuticas, y se someten a una evaluación detallada después de cualquier procedimiento.

Fast and Universal Kohn-Sham Density Functional Theory Algorithm for Warm Dense Matter to Hot Dense Plasma.

Understanding many processes, e.g., fusion experiments, planetary interiors, and dwarf stars, depends strongly on microscopic physics modeling of warm dense matter and hot dense plasma. This complex state of matter consists of a transient mixture of degenerate and nearly free electrons, molecules, and ions. This regime challenges both experiment and analytical modeling, necessitating predictive ab initio atomistic computation, typically based on quantum mechanical Kohn-Sham density functional theory (KS-DFT). However, cubic computational scaling with temperature and system size prohibits the use of DFT through much of the warm dense matter regime. A recently developed stochastic approach to KS-DFT can be used at high temperatures, with the exact same accuracy as the deterministic approach, but the stochastic error can converge slowly and it remains expensive for intermediate temperatures (<50 eV). We have developed a universal mixed stochastic-deterministic algorithm for DFT at any temperature. This approach leverages the physics of KS-DFT to seamlessly integrate the best aspects of these different approaches. We demonstrate that this method significantly accelerated self-consistent field calculations for temperatures from 3 to 50 eV, while producing stable molecular dynamics and accurate diffusion coefficients.

Hiding Ignorance Using High Dimensions.

The absence of information-entirely or partly-is called ignorance. Naturally, one might ask if some ignorance of a whole system will imply some ignorance of its parts. Our classical intuition tells us yes, however quantum theory tells us no: it is possible to encode information in a quantum system so that despite some ignorance of the whole, it is impossible to identify the unknown part [T. Vidick and S. Wehner, Phys. Rev. Lett. 107, 030402 (2011).PRLTAO0031-900710.1103/PhysRevLett.107.030402]. Experimentally verifying this counterintuitive fact requires controlling and measuring quantum systems of high dimension (d>9). We provide this experimental evidence using the transverse spatial modes of light, a powerful resource for testing high-dimensional quantum phenomena.

Blocking substance P signaling reduces musculotendinous and dermal fibrosis and sensorimotor declines in a rat model of overuse injury.

Purpose/Aim: Substance P-NK-1R signaling has been implicated in fibrotic tendinopathies and myositis. Blocking this signaling with a neurokinin 1 receptor antagonist (NK1RA) has been proposed as a therapeutic target for their treatment.Materials and Methods: Using a rodent model of overuse injury, we pharmacologically blocked Substance P using a specific NK1RA with the hopes of reducing forelimb tendon, muscle and dermal fibrogenic changes and associated pain-related behaviors. Young adult rats learned to pull at high force levels across a 5-week period, before performing a high repetition high force (HRHF) task for 3 weeks (2 h/day, 3 days/week). HRHF rats were untreated or treated in task weeks 2 and 3 with the NK1RA, i.p. Control rats received vehicle or NK1RA treatments.Results: Grip strength declined in untreated HRHF rats, and mechanical sensitivity and temperature aversion increased compared to controls; these changes were improved by NK1RA treatment (L-732,138). NK1RA treatment also reduced HRHF-induced thickening in flexor digitorum epitendons, and HRHF-induced increases of TGFbeta1, CCN2/CTGF, and collagen type 1 in flexor digitorum muscles. In the forepaw upper dermis, task-induced increases in collagen deposition were reduced by NK1RA treatment.Conclusions: Our findings indicate that Substance P plays a role in the development of fibrogenic responses and subsequent discomfort in forelimb tissues involved in performing a high demand repetitive forceful task.

Mixed quantum-classical approach to model non-adiabatic electron-nuclear dynamics: Detailed balance and improved surface hopping method.

We develop a density matrix formalism to describe coupled electron-nuclear dynamics. To this end, we introduce an effective Hamiltonian formalism that describes electronic transitions and small (quantum) nuclear fluctuations along a classical trajectory of the nuclei. Using this Hamiltonian, we derive equations of motion for the electronic occupation numbers and for the nuclear coordinates and momenta. We show that, in the limit, when the number of nuclear degrees of freedom coupled to a given electronic transition is sufficiently high (i.e., the strong decoherence limit), the equations of motion for the electronic occupation numbers become Markovian. Furthermore, the transition rates in these (rate) equations are asymmetric with respect to the lower-to-higher energy transitions and vice versa. In thermal equilibrium, such asymmetry corresponds to the detailed balance condition. We also study the equations for the electronic occupations in the non-Markovian regime and develop a surface hopping algorithm based on our formalism. To treat the decoherence effects, we introduce additional "virtual" nuclear wave packets whose interference with the "real" (physical) wave packets leads to the reduction in coupling between the electronic states (i.e., decoherence) as well as to the phase shifts that improve the accuracy of the numerical approach. Remarkably, the same phase shifts lead to the detailed balance condition in the strong decoherence limit.

Nutritional adequacy and content of food bank parcels in Oxfordshire, UK: a comparative analysis of independent and organisational provision.

BACKGROUND: Food bank use has increased significantly in the UK. With the rise in demand, it is imperative that users are receiving food parcels that meet their requirements. The present study aimed to explore whether typical food parcels, supplied by The Trussell Trust and independent food banks, were meeting the daily nutrient and energy requirements of an adult user. METHODS: The Trussell Trust (n = 2) and independent food banks (n = 9) were surveyed in Oxfordshire, UK. Data were collected on food bank use, resources, donations and parcel content. The energy and nutrient contents of a representative parcel were compared with the average dietary reference values (DRVs) for an adult. Additional comparisons were made between The Trussell Trust and independent provision. RESULTS: Parcels provided energy, carbohydrate, sugar, protein and fibre contents that significantly exceeded the DRVs. In total, 62.2% of energy was provided as carbohydrate and 569% of the DRV was provided by sugars. The vitamin D and retinol content of the parcels was significantly lower than the DRVs, meeting 25% and 27% of users' needs respectively; provision of all other micronutrients exceeded the DRVs. The Trussell Trust's parcels provided significantly less vitamin D and copper than independent parcels. CONCLUSIONS: Food bank parcels distributed in Oxfordshire, UK, exceeded energy requirements and provided disproportionately high sugar and carbohydrate and inadequate vitamin A and vitamin D compared to the UK guidelines. Improved links with distributors and access to cold food storage facilities would help to address these issues, via increased fresh food provision.

ScribeMD: Mixed-methods analysis of a pen pal program in undergraduate medical education.

Introduction: A growing emphasis on humanistic medical care has led to the development of programs to imbue more humanistic values into training physicians. The ScribeMD intra-class pen pal program is a narrative medicine tool designed to meet this need with a focus on the journey through medical education. This study intends to evaluate the efficacy of this novel program on the participants' professional identity formation (PIF), emotional intelligence development (EID), and narrative competency improvement (NCI).Methods: This program evaluation involved quantitative and qualitative survey solicitations from first and second-year medical student participants and controls. An efficacy-triangulation model was developed as a quantitative outcome-measuring tool linking objective, writing prompts, and survey data.Results: The quantitative results showed statistically significant improvements in line with the Efficacy Triangulation Model in the participant group. Qualitatively, reflective and insight-driven gains were elicited, as were notable themes of personal and community improvements.Conclusion: ScribeMD poses a unique avenue for the development of more humanistic physicians during their medical education. We recommend additional development of the Efficacy Triangulation Model as well as the program design itself. We also recommend the piloting of this program in other healthcare-education settings both with medical education and other health professions.

Cryptosporidium parvum Subtilisin-Like Serine Protease (SUB1) Is Crucial for Parasite Egress from Host Cells.

Despite the severity and global burden of Cryptosporidium infection, treatments are less than optimal, and there is no effective vaccine. Egress from host cells is a key process for the completion of the life cycle of apicomplexan parasites. For Plasmodium species, subtilisin-like serine protease (SUB1) is a key mediator of egress. For Toxoplasma species, calcium-dependent protein kinases (CDPKs) are critical. In this study, we characterized Cryptosporidium SUB1 expression and evaluated its effect using an infection model. We found increased expression between 12 and 20 h after in vitro infection, prior to egress. We induced silencing of SUB1 (ΔSUB1) mRNA using SUB1 single-stranded antisense RNA coupled with human Argonaute 2. Silencing of SUB1 mRNA expression did not affect parasite viability, excystation, or invasion of target cells. However, knockdown led to a 95% decrease in the proportion of released merozoites in vitro (P < 0.0001). In contrast, silencing of CDPK5 had no effect on egress. Overall, our results indicate that SUB1 is a key mediator of Cryptosporidium egress and suggest that interruption of the life cycle at this stage may effectively inhibit the propagation of infection.

Common latitudinal gradients in functional richness and functional evenness across marine and terrestrial systems.

Functional diversity is an important aspect of biodiversity, but its relationship to species diversity in time and space is poorly understood. Here we compare spatial patterns of functional and taxonomic diversity across marine and terrestrial systems to identify commonalities in their respective ecological and evolutionary drivers. We placed species-level ecological traits into comparable multi-dimensional frameworks for two model systems, marine bivalves and terrestrial birds, and used global species-occurrence data to examine the distribution of functional diversity with latitude and longitude. In both systems, tropical faunas show high total functional richness (FR) but low functional evenness (FE) (i.e. the tropics contain a highly skewed distribution of species among functional groups). Functional groups that persist toward the poles become more uniform in species richness, such that FR declines and FE rises with latitude in both systems. Temperate assemblages are more functionally even than tropical assemblages subsampled to temperate levels of species richness, suggesting that high species richness in the tropics reflects a high degree of ecological specialization within a few functional groups and/or factors that favour high recent speciation or reduced extinction rates in those groups.