Flying bats use serial sampling to locate odour sources

Olfactory tracking generally sacrifices speed for sensitivity, but some fast-moving animals appear surprisingly efficient at foraging by smell. Here, we analysed the olfactory tracking strategies of flying bats foraging for fruit. Fruit- and nectar-feeding bats use odour cues to find food despite the sensory challenges derived from fast flight speeds and echolocation. We trained Jamaican fruit-eating bats ( Artibeus jamaicensis ) to locate an odour reward and reconstructed their flight paths in three-dimensional space. Results confirmed that bats relied upon olfactory cues to locate a reward. Flight paths revealed a combination of odour- and memory-guided search strategies. During ‘inspection flights’, bats significantly reduced flight speeds and flew within approximately 6 cm of possible targets to evaluate the presence or absence of the odour cue. This behaviour combined with echolocation explains how bats maximize foraging efficiency while compensating for trade-offs associated with olfactory detection and locomotion.

Evaluation of Paromomycin Treatment for Cryptosporidium serpentis Infection in Eastern Indigo Snakes (Drymarchon couperi)

Thirty-four eastern indigo snakes ( Drymarchon couperi ) naturally infected with Cryptosporidium serpentis were randomly divided into two groups. The first group received 360 mg/kg paromomycin twice weekly in a food item for six weeks, while the second group received the food item with no treatment. Cloacal swabs were collected every two months for six months to measure C. serpentis shedding by quantitative polymerase chain reaction testing (qPCR). Snakes that were qPCR negative after six 6 months were immunosuppressed with a single dose of 4 mg/kg dexamethasone sodium-phosphate SC. These snakes were then screened by qPCR for an additional 6 months as described above. Snakes that were qPCR negative after one year of serial sampling were then re-evaluated for C. serpentis via gastric biopsy for histological and qPCR analyses. The paromomycin-treated group were significantly (p=0.008) more likely to test qPCR negative (8/17; 47%, 95% Confidence Interval [CI]: 23.2-70.7) than the control snakes (1/17; 5.8%, 95% CI: 0.01-16.9) prior to immunosuppression. However, there was no significant difference (p=0.5) in C. serpentis status following immunosuppression as only 2/17 (11.7%, 95% CI: 0.01-26.9) paromomycin-treated snakes were qPCR negative six months after immunosuppression compared to 1/17 (5.8%, 95% CI: 95% CI: 0.01-16.9) control snakes. These findings suggest that 360 mg/kg paromomycin twice weekly for six weeks in a food item is ineffective in eliminating C. serpentis in naturally infected D. couperi .

Prospective real-world study on the pharmacokinetics of pembrolizumab in patients with solid tumors

BackgroundDosing schemes of pembrolizumab (anti-programmed cell death protein 1 monoclonal antibody) are solely based on pharmacokinetic (PK) modelling derived from phase I–III trials. The current study aimed to determine factors affecting PK and its relationship with clinical outcome in the real-world setting.MethodsAdvanced-stage cancer patients, who were treated with pembrolizumab monotherapy (2 mg/kg Q3W or 200 mg flat Q3W), were prospectively included for serial sampling to obtain trough concentrations. A PK model was generated, covariate effects assessed and internally validated by a bootstrap procedure. PK parameters were related to overall survival (OS) and the occurrence of immune-related adverse events (irAEs).Results588 serum samples derived from 122 patients with (non-)small-cell lung cancer ([N]SCLC), malignant pleural mesothelioma (MPM), melanoma and urothelial cell cancer (UCC) were analyzed. Median follow-up was 2.2 years. A one-compartment PK model was generated: body surface area (BSA) and serum albumin had a significant effect on drug clearance (CL; covariate estimate 1.46 and −1.43, respectively), and serum lactate dehydrogenase (LDH) on the distribution volume(Vd; 0.34). A significant inverse CL–OS relationship was determined for NSCLC (HR:1.69; 95%CI1.07–2.68; p=0.024) and MPM (HR: 3.29; 95% CI 1.08 to 10.09; p=0.037), after correction for prognostic factors, which could not confirmed for melanoma (p=0.22) or UCC (p=0.34). No relationship could be determined between CL and grade >3 irAEs (p=0.70).ConclusionsHigh interpatient variability of pembrolizumab PK is determined by BSA and serum albumin (on CL) and LDH (on Vd). A strong inverse CL–OS relationship was demonstrated for NSCLC and MPM, which could not be observed for melanoma and UCC. The findings suggest that personalized dosing should be prospectively explored.

SARS-CoV-2 antibody immunoassays in serial samples reveal earlier seroconversion in acutely ill COVID-19 patients developing ARDS

Objectives During the COVID-19 pandemic, SARS-CoV-2 antibody testing has been suggested for (1) screening populations for disease prevalence, (2) diagnostics, and (3) guiding therapeutic applications. Here, we conducted a detailed clinical evaluation of four Anti-SARS-CoV-2 immunoassays in samples from acutely ill COVID-19 patients and in two negative cohorts. Methods 443 serum specimens from serial sampling of 29 COVID-19 patients were used to determine clinical sensitivities. Patients were stratified for the presence of acute respiratory distress syndrome (ARDS). Individual serum specimens from a pre-COVID-19 cohort of 238 healthy subjects and from a PCR-negative clinical cohort of 257 patients were used to determine clinical specificities. All samples were measured side-by-side with the Anti-SARS-CoV-2-ELISA (IgG), Anti-SARS-CoV-2-ELISA (IgA) and Anti-SARS-CoV-2-NCP-ELISA (IgG) (Euroimmun AG, Lübeck, Germany) and the Elecsys Anti-SARS-CoV-2 ECLIA (Roche Diagnostics International, Rotkreuz, Switzerland). Results Median seroconversion occurred earlier in ARDS patients (8–9 days) than in non-ARDS patients (11–17 days), except for EUR N-IgG. Rates of positivity and mean signal ratios in the ARDS group were significantly higher than in the non-ARDS group. Sensitivities between the four tested immunoassays were equivalent. In the set of negative samples, the specificity of the Anti-SARS-CoV-2-ELISA (IgA) was lower (93.9%) compared to all other assays (≥98.8%) and the specificity of Anti-SARS-CoV-2-NCP-ELISA (IgG) was lower (98.8%) than that of Elecsys Anti-SARS-CoV-2 (100%). Conclusions Serial sampling in COVID-19 patients revealed earlier seroconversion and higher signal ratios of SARS-CoV-2 antibodies as a potential risk marker for the development of ARDS, suggesting a utility for antibody testing in acutely diseased patients.

Effect of Patent Foramen Ovale (PFO) Closure After Stroke on Circulatory Biomarkers

Objective:To determine the influence of patent foramen ovale (PFO) closure on circulatory biomarkers.Methods:Consecutive PFO-related stroke patients were prospectively enrolled and followed with serial sampling of cardiac atrial and venous blood, pre and post PFO closure over time. Candidate biomarkers were identified by mass spectrometry in a discovery cohort first, and lead candidates were validated in an independent cohort.Results:PFO stroke patients (n=254) were recruited and followed up to four years (median: 2.01; IQR: 0.77∼2.54). Metabolite profiling in discovery cohort (n=12) identified homocysteine as the most significantly decreased factor in intra-cardiac plasma after PFO closure (FDR=0.001). This was confirmed in validation cohort (n=181), where intra-cardiac total homocysteine (tHcy) reduced immediately in patients with complete closure, but not in those with residual shunting, suggesting association of PFO shunting with tHcy elevation (β: 0.115; 95% CI: 0.047∼0.183; p=0.001). tHcy reduction was more dramatic in left atrium than right (p<0.001), suggesting clearance through pulmonary circulation. Long-term effect of PFO closure was also monitored and compared to medical treatment alone (n=61). Complete PFO closure resulted in long-term tHcy reduction in peripheral blood, whereas medical therapy alone showed no effect (β: -0.208; 95% CI: -0.375∼-0.058; p=0.007). Residual shunting was again independently associated with persistently elevated tHcy (β: 0.184; 95% CI: 0.051∼0.316; p=0.007).Conclusions:PFO shunting may contribute to circulatory tHcy elevation, which is renormalized by PFO closure. PFO is not just a door for clots, but may itself enhance clot formation and injure neurovasculature by clot-independent mechanisms. Biomarkers such as tHcy can potentially serve as cost-effective measures of residual shunting and neurovascular risk for PFO stroke.

Human endogenous oxytocin and its neural correlates show adaptive responses to social touch based on recent social context

Both oxytocin (OT) and touch are key mediators of social attachment. In rodents, tactile stimulation elicits endogenous release of OT, potentially facilitating attachment and other forms of prosocial behavior, yet the relationship between endogenous OT and neural modulation remains unexplored in humans. Using serial sampling of plasma hormone levels during functional neuroimaging, we show that contextual circumstances of social touch facilitate or inhibit not only current hormonal and brain responses, but also calibrate later responses. Namely, touch from a romantic partner enhanced subsequent OT release for touch from an unfamiliar stranger, yet OT responses to partner touch were dampened following stranger touch. Hypothalamus and dorsal raphe activation reflected plasma OT changes during the initial interaction. In the subsequent social interaction, OT modulation depended on the previous interaction, mediated by precuneus and parietal-temporal cortex pathways, including a region of medial prefrontal cortex that also covaried with plasma cortisol. These findings demonstrate that hormonal neuromodulation during successive human social interactions is adaptive to social context, and they point to mechanisms that flexibly calibrate receptivity in social encounters.

Is the Presence of Leptospira in the Environment Merely Random? an Epidemiological Explanation Based on Serial Analysis of Water Samples

Human leptospirosis cannot be investigated without studying zoonotic and environmental as-pects of the disease. The objectives of this study are to explore the abundance of Leptospira in dif-ferent climate zones of Sri Lanka and to describe the presence of Leptospira in same water source at different time points. First, water and soil samples were collected from whole-island, secondly, water sampling continued only in dry-zone, finally serial sampling of water from ten open wells was performed at five different time points. Quantitative PCR for water and metagenomic se-quencing for soil were used to detect Leptospira. In first component, 2 out of 12 water sites were positive and both are situated in wet-zone. Very small quantities of Genus Leptospira was detect-ed by metagenomic analysis of soil. Only 5 out of 26 samples were positive in the second compo-nent. Six, five, four, five, six wells were positive respectively in serial measurements of third component. All wells were positive at least one measurement while only one well was positive in all measurements. Closer to tank and higher distance from main road were significant risk fac-tors associated with well positivity. Presence of Leptospira seems not consistent indicating ran-dom abundance of Leptospira in natural environment.

SARS-CoV-2 antibody immunoassays in serial samples reveal earlier seroconversion in acutely ill COVID-19 patients developing ARDS

ObjectivesDuring the COVID-19 pandemic, SARS-CoV-2 antibody testing has been suggested for (1) screening populations for disease prevalence, (2) diagnostics, and (3) guiding therapeutic applications. Here, we conducted a detailed clinical evaluation of four Anti-SARS-CoV-2 immunoassays in samples from acutely ill COVID-19 patients and in two negative cohorts.Methods443 serum specimens from serial sampling of 29 COVID-19 patients were used to determine clinical sensitivities. Patients were stratified for the presence of acute respiratory distress syndrome (ARDS). Individual serum specimens from a pre-COVID-19 cohort of 238 healthy subjects and from a PCR-negative clinical cohort of 257 patients were used to determine clinical specificities. All samples were measured side-by-side with the Anti-SARS-CoV-2-ELISA (IgG), Anti-SARS-CoV-2-ELISA (IgA) and Anti-SARS-CoV-2-NCP-ELISA (IgG) (Euroimmun AG, Lübeck, Germany) and the Elecsys Anti-SARS-CoV-2 ECLIA (Roche Diagnostics International, Rotkreuz, Switzerland).ResultsMedian seroconversion occurred earlier in ARDS patients (8-9 days) than in non-ARDS patients (11-17 days), except for EUR N-IgG. Rates of positivity and mean signal ratios in the ARDS group were significantly higher than in the non-ARDS group. Sensitivities between the four tested immunoassays were equivalent. In the set of negative samples, the specificity of the Anti-SARS-CoV-2-ELISA (IgA) was lower (93.9 %) compared to all other assays (≥98.8 %) and the specificity of Anti-SARS-CoV-2-NCP-ELISA (IgG) was lower (98.8 %) than that of Elecsys Anti-SARS-CoV-2 (100 %).ConclusionsSerial sampling in COVID-19 patients revealed earlier seroconversion and higher signal ratios of SARS-CoV-2 antibodies as a potential risk marker for the development of ARDS, suggesting a utility for antibody testing in acutely diseased patients.