Sex-specific ornament evolution is a consistent feature of climatic adaptation across space and time in dragonflies.

Adaptation to different climates fuels the origins and maintenance of biodiversity. Detailing how organisms optimize fitness for their local climates is therefore an essential goal in biology. Although we increasingly understand how survival-related traits evolve as organisms adapt to climatic conditions, it is unclear whether organisms also optimize traits that coordinate mating between the sexes. Here, we show that dragonflies consistently adapt to warmer climates across space and time by evolving less male melanin ornamentation-a mating-related trait that also absorbs solar radiation and heats individuals above ambient temperatures. Continent-wide macroevolutionary analyses reveal that species inhabiting warmer climates evolve less male ornamentation. Community-science observations across 10 species indicate that populations adapt to warmer parts of species' ranges through microevolution of smaller male ornaments. Observations from 2005 to 2019 detail that contemporary selective pressures oppose male ornaments in warmer years; and our climate-warming projections predict further decreases by 2070. Conversely, our analyses show that female ornamentation responds idiosyncratically to temperature across space and time, indicating the sexes evolve in different ways to meet the demands of the local climate. Overall, these macro- and microevolutionary findings demonstrate that organisms predictably optimize their mating-related traits for the climate just as they do their survival-related traits.

The role of biodegradable stents in the management of benign and malignant oesophageal strictures: A cohort study.

BACKGROUND: Oesophageal strictures can be caused by benign or malignant processes. Up to 10% of patients with a benign stricture are refractory to pneumatic dilatation and may benefit from biodegradable stent (BD) insertion. Biodegradable stents also have a role in malignant oesophageal strictures to facilitate enteral nutrition while staging or neo-adjuvant treatment is completed. The aim of this study was to review the safety and efficacy of BD stents in the management of benign or malignant oesophageal strictures. METHODS: A single centre retrospective cohort study was performed. Dysphagia was graded before and after stenting using a validated score. All patients were followed up for at least 30 days and all adverse events were recorded. RESULTS: Twenty eight stents were inserted in 20 patients; 11 for malignant and 17 for benign disease. One further attempted stenting was impossible due to a high benign stricture. There were no perforations and the 30-day mortality rate was zero. Mean dysphagia scores improved from 2.65 to 1.00 (p value <0.001) in benign disease and from 3.27 to 1.36 (p value <0.001) in patients with malignant disease. Surgical resection was not compromised following stent insertion in the malignant group. CONCLUSIONS: Biodegradable stent insertion is a safe and efficacious adjunct in the treatment of benign and malignant oesophageal strictures. In malignant disease, BD stent insertion can maintain enteral nutrition while staging or neo-adjuvant therapy is completed without adversely impacting on surgical resection.

¹H NMR metabolic profiling of plasma reveals additional phenotypes in knockout mouse models.

The International Mouse Phenotyping Consortium program has been established to ascribe biological functions to systematically knocked-out (KO) genes by in vivo and ex vivo phenotyping. The plasma clinical chemistry screen includes an assessment of liver, kidney, and bone function and provides a basic lipid profile and histopathology reports on 32 tissues. We report on the inclusion of plasma analysis by proton nuclear magnetic resonance ((1)H NMR) spectroscopy. (1)H NMR spectroscopy data are summarized from 116 running baseline controls with 18 homozygous and 2 heterozygous KO mouse lines along with wild-type controls (typically n = 7 per gender). For the baseline group, the intersample variation of (1)H NMR glucose measurement was 12%, and the (1)H NMR spectroscopy data were influenced by gender and feeding status. There were good correlations between the clinical chemistry and the (1)H NMR spectroscopy measurements for glucose, triglycerides, and HDL cholesterol. Significant differences were observed in two KO lines, Agl (MGI: 1924809) and Bbs5 (MGI: 1919819), by (1)H NMR spectroscopy, clinical chemistry, and histopathology. In a further two KO lines, Elmod1 (MGI: 3583900) and Emc10 (MGI: 1916933), (1)H NMR metabolic differences were observed, but no other ex vivo changes were detected. In the remaining 16 lines, no ex vivo abnormal phenotypes were observed. Plasma (1)H NMR spectroscopy can therefore provide a novel perspective on the function of knocked-out genes.

The role of esophageal stents in the management of esophageal anastomotic leaks and benign esophageal perforations.

OBJECTIVE: The aim of this review was to assess the safety and effectiveness of esophageal stents in the management of benign esophageal perforation and in the management of esophageal anastomotic leaks. BACKGROUND: Benign esophageal perforation and postoperative esophageal anastomotic leak are often encountered. Endoscopic placement of esophageal stent across the site of leakage might help control the sepsis and reduce the mortality and morbidity. METHODS: All the published case series reporting the use of metallic and plastic stents in the management of postoperative anastomotic leaks, spontaneous esophageal perforations, and iatrogenic esophageal perforations were identified from MEDLINE, EMBASE, and PubMed (1990-2012). Primary outcomes assessed were technical success rates and complete healing rates. Secondary outcomes assessed were stent migration rates, stent perforation rates, duration of hospital stay, time to stent removal, and mortality rates. A pooled analysis was performed and subgroup analysis was performed for plastic versus metallic stents and anastomotic leaks versus perforations separately. RESULTS: A total of 27 case series with 340 patients were included. Technical and clinical success rates of stenting were 91% and 81%, respectively. Stent migration rates were significantly higher with plastic stents than with metallic stents (40/148 vs 13/117 patients, respectively; P = 0.001). Patients with metallic stents had significantly higher incidence of postprocedure strictures (P = 0.006). However, patients with plastic stents needed significantly higher number of reinterventions (P = 0.005). Mean postprocedure hospital stay varied from 8 days to 51 days. There was no significant difference in the primary or secondary outcomes when stenting was performed for anastomotic leaks or perforations. CONCLUSIONS: Endoscopic management of esophageal anastomotic leaks and perforations with the use of esophageal stents is technically feasible. It seems to be safe and effective when performed along with mediastinal or pleural drainage. Esophageal stent can, therefore, be considered as a treatment option in the management of patients who present early after esophageal perforation or anastomotic leak with limited mediastinal or pleural contamination.

Overexpression of chimaeric murine/ovine PrP (A136H154Q171) in transgenic mice facilitates transmission and differentiation of ruminant prions.

Development of transgenic mouse models expressing heterologous prion protein (PrP) has facilitated and advanced in vivo studies of prion diseases affecting humans and animals. Here, novel transgenic mouse lines expressing a chimaeric murine/ovine (Mu/Ov) PrP transgene, including amino acid residues alanine, histidine and glutamine at ovine polymorphic codons 136, 154 and 171 (A136H154Q171), were generated to provide a means of assessing the susceptibility of the ovine AHQ allele to ruminant prion diseases in an in vivo model. Transmission studies showed that the highest level of transgene overexpression, in Tg(Mu/OvPrP(AHQ))EM16 (EM16) mice, conferred high susceptibility to ruminant prions. Highly efficient primary transmission of atypical scrapie from sheep was shown, irrespective of donor sheep PrP genotype, with mean incubation periods (IPs) of 154­178 days post-inoculation (p.i.), 100% disease penetrance and early Western blot detection of protease-resistant fragments (PrP(res)) of the disease-associated isoform, PrP(Sc), in EM16 brain from 110 days p.i. onwards. EM16 mice were also highly susceptible to classical scrapie and bovine spongiform encephalopathy (BSE), with mean IPs 320 and 246 days faster, respectively, than WT mice. Primary passage of atypical scrapie, classical scrapie and BSE showed that the PrP(res) profiles associated with disease in the natural host were faithfully maintained in EM16 mice, and were distinguishable based on molecular masses, antibody reactivities and glycoform percentages. Immunohistochemistry was used to confirm PrP(Sc) deposition in brain sections from terminal phase transmissible spongiform encephalopathy-challenged EM16 mice. The findings indicate that EM16 mice represent a suitable bioassay model for detection of atypical scrapie infectivity and offer the prospect of differentiation of ruminant prions.

Sweating Out the Circadian Rhythm: A Technical Review.

Circadian dysfunction or dysregulation is associated with many chronic morbidities. Current state-of-art technologies do not provide an accurate estimation of the extent of disease affliction. Recent advances call for using wearables for improving management and diagnosis of circadian related disorders. Sweat contains an abundance of relevant biomarkers like cortisol, DHEA, and so forth, which could be leveraged toward tracking the user's chronobiology. In this article, we provide a review of the key developments in the field of wearable sensors for circadian technologies. We highlight the value of using sweat along with portable electronics toward developing state-of-the-art platforms for efficient diagnosis and management of chronic conditions. Finally, we discuss challenges and opportunities for using wearable sweat sensors for circadian diagnosis and disease management.

Development of a flexible, sweat-based neuropeptide Y detection platform.

Neuropeptide Y (NPY) biomarker levels have a close association with the diagnosis of Major Depression Disorder (MDD) and anxiety disorders. Quantifying NPY in correlation to self-reported symptoms will be an important measure to ensure a relatively uniform diagnosis and help with disease prognosis of these disorders. The work presented is a novel, passive eccrine sweat based, electrochemical detection platform for quantification of NPY biomarker levels. The paper offers a comparison between non-porous and porous sensor platforms using various electrochemical detection techniques. This work uses a novel strategy towards designing an optimal nanobioelectronic interface to measure NPY. The portability aspect of this detection platform is discussed by the demonstration a novel, portable EmStat Pico based electronic platform. The detection limit of the sensor is 10 pg mL-1 and its range is 20-500 pg mL-1. The NPY detection platform is envisioned to be a wearable point-of need monitoring system for management of chronic anxiety disorders and MDD.

A Combinatorial Electrochemical Biosensor for Sweat Biomarker Benchmarking.

Misclassification of an acute disease condition as chronic and vice versa by electrochemical sweat biomarker sensors can cause significant psychological, emotional, and financial stress among patients. To achieve higher accuracy in distinguishing between a chronic condition and an acute condition, there is a need to establish a reference biomarker to index the actual chronic disease biomarker of interest by combinatorial sensing. This work provides the first technological proof of leveraging the chloride ion content in sweat for a combinatorial sweat biomarker benchmarking scheme. In this scheme, the sweat chloride ion has been demonstrated as the reference/indexing biomarker, while sweat cortisol has been studied as the disease biomarker of interest. Label-free affinity biosensing is achieved by using a two-electrode electrochemical system on a flexible substrate suitable for wearable applications. The electrochemical stability of the fabricated electrodes for biosensing applications was studied by open-circuit potential measurements. Attenuated total reflectance-Fourier transform infrared spectroscopy spectra validate the crosslinker-antibody binding chemistry. Concentration-dependent analyte-capture probe binding induces a modulation in the electrical properties (charge transfer resistance and double-layer capacitance) at the electrode-sweat buffer interface, which are transduced by nonfaradaic electrochemical impedance spectroscopy (EIS). Calibration dose responses for the sensor for cortisol (5-200 ng/mL) and chloride (10-100 mM) detection were evaluated in synthetic (pH 6) and pooled human sweat (R2 > 0.95). The variation in the cortisol sensor response due to fluctuations in sweat chloride levels and the significance of reporting normalized biomarker levels were demonstrated to further emphasize the need for biomarker benchmarking in electrochemical sensors.

Distal tibiofibular syndesmosis reconstruction using a free hamstring autograft.

BACKGROUND: Chronic instability of the distal tibiofibular syndesmosis and its treatment is infrequently described in the literature. We report our results for treating this condition with a reconstruction based on restoration of near normal anatomy with a hamstring autograft. MATERIALS AND METHODS: Eight patients, who had chronic distal tibiofibular syndesmosis instability diagnosed arthroscopically underwent reconstruction of the distal anterior tibiofibular ligament and the transverse interosseus ligament using a free semi-tendinosis hamstring autograft. A radiographic and clinical review of the patients was performed. The average followup was 39 (range, 9 to 86) months. RESULTS: The postoperative visual analogue pain score was 19 out of 100 compared to 73 out of 100 preoperatively. The postoperative mean AOFAS score was 85.4 (range, 49 to 100), the SF-36 score was 81 (range, 56 to 92) and the Maryland foot score was 89.3 (range, 63 to 100). CONCLUSION: Chronic instability of the distal tibiofibular syndesmosis is an infrequent problem but disabling when it occurs. Our results show an improved VAS score for pain, improved swelling and instability symptoms as well as SF-36, AOFAS and Maryland scores. We would recommend this method to reconstruct the anterior tibiofibular ligament and the transverse interosseus ligament which has failed to respond to debridement alone.

The effect of steroid treatment with inhaled budesonide or intravenous methylprednisolone on phosgene-induced acute lung injury in a porcine model.

Toxic industrial chemicals e.g., phosgene, are widely used as reactive intermediates in industrial processes. Inhalation exposure to these chemicals can result in life-threatening acute lung injury (ALI), to which no specific antidote exists. This study aimed to assess the potential benefit of steroids in treating phosgene induced ALI. Anesthetized pigs were instrumented, exposed to phosgene Ct 2000 mg.min.m(-3) (Ct is the product of concentration [mg.m(-3)] x time [min]), and ventilated with intermittent positive pressure ventilation before being randomized to study part 1: treatment with intravenous glucose saline (20 mL) or methylprednisolone (12.5 mg.kg(-1) in 20 mL) 6 h postexposure or study part 2: treatment with inhaled glucose saline (2 mL) or budesonide (2 mL of 0.5 mg.mL(-1) solution) at 1, 6, 12, and 18 h postexposure. Biochemical parameters and animal physiology were monitored to 24 h postexposure. The results show no change in mortality, lung edema, or shunt fraction; however, some beneficial effects on cardiac parameters e.g., stroke volume, left ventricular stroke work, were noted. Steroids were neither beneficial nor detrimental in the treatment of phosgene induced ALI. This study does not support the use of steroids alone as a treatment, but their use in a combined therapy strategy should be investigated.

CortiWatch: watch-based cortisol tracker.

Sweat-based analytics have recently caught the attention of researchers and medical professionals alike because they do not require professionally trained personnel or invasive collection techniques to obtain a sample. The following presents a small form-factor biosensor for reporting physiological ranges of cortisol present in ambient sweat (8-151 ng/ml). This device obtains cortisol measurements through low volumes of unstimulated sweat from the user's wrist. We designed a potentiostatic circuit on a printed circuit board to perform electrochemical testing techniques. The detection modality developed for quantifying sensor response to varying cortisol concentrations is a current based electrochemical technique, chronoamperometry (CA). From the results, the sensor can detect cortisol in the physiologically relevant ranges of cortisol; thus, the sensor is a noninvasive, label free, cost-effective solution for tracking cortisol levels for circadian diagnostics.

Computer-Assisted Tracking of Chlamydomonas Species.

The green algae Chlamydomonas reinhardtii is a model system for motility in unicellular organisms. Photo-, gravi-, and chemotaxis have previously been associated with C. reinhardtii, and observing the extent of these responses within a population of cells is crucial for refining our understanding of how this organism responds to changing environmental conditions. However, manually tracking and modeling a statistically viable number of samples of these microorganisms is an unreasonable task. We hypothesized that automated particle tracking systems are now sufficiently advanced to effectively characterize such populations. Here, we present an automated method to observe C. reinhardtii motility that allows us to identify individual cells as well as global information on direction, speed, and size. Nutrient availability effects on wild-type C. reinhardtii swimming speeds, as well as changes in speed and directionality in response to light, were characterized using this method. We also provide for the first time the swimming speeds of several motility-deficient mutant lines. While our present effort is focused around the unicellular green algae, C. reinhardtii, we confirm the general utility of this approach using Chlamydomonas moewusii, another member of this genus which contains over 300 species. Our work provides new tools for evaluating and modeling motility in this model organism and establishes the methodology for conducting similar experiments on other unicellular microorganisms.

Analyzing quantitative light scattering spectra of phantoms measured with optical coherence tomography.

We demonstrate the ability of multiple forms of optical coherence tomography (OCT) in the frequency domain to quantitatively size scatterers. Combined with a variety of distinct phantoms, we gain insight into the measurement uncertainties associated with using scattering spectra to size scatterers. We size spherical scatterers on a surface using swept-source OCT with an analysis based on a simple slab-mode resonance model. Automating this technique, a two-dimensional (2-D) image is created by raster scanning across a surface phantom designed to have a distinct size transition to demonstrate accuracy and repeatability. We also investigate the potential of a novel sphere-nanotube structure as a quantitative calibration artifact for use in comparing measured intensity and phase scattering spectra directly to Mie theory predictions. In another experiment, we demonstrate tissue-relevant sizing of scatterers as small as 5 microm on a surface by use of a Fourier domain OCT system with 280 nm of bandwidth from a supercontinuum source. We perform an uncertainty analysis for our high-resolution sizing system, estimating a sizing error of 9% for measurements of spheres with a diameter of 15 microm. With appropriate modifications, our uncertainty analysis has general applicability to other sizing techniques utilizing scattering spectra.

Protective ventilation strategies in the management of phosgene-induced acute lung injury.

Phosgene is a chemical widely used in the plastics industry and has been used in warfare. It produces a life-threatening pulmonary edema within hours of exposure, to which no specific antidote exists. This study aims to examine the pathophysiological changes seen with low tidal volume ventilation (protective ventilation (PV)) strategies compared to conventional ventilation (CV), in a model of phosgene-induced acute lung injury. Anesthetized pigs were instrumented and exposed to phosgene (concentration x time (Ct), 2,350 mg x min x m(-3)) and then ventilated with intermittent positive pressure ventilation (tidal volume (TV) = 10 ml x kg(-1); positive end expiratory pressure, 3 cm H2O; frequency, 20 breaths x min(-1); fractional concentration of inspired oxygen, 0.24), monitored for 6 hours after exposure, and then randomized into treatment groups: CV, PV (A) or (B) (TV, 8 or 6 ml x kg(-1); positive end expiratory pressure, 8 cm H2O; frequency, 20 or 25 breaths x min(-1); fractional concentration of inspired oxygen, 0.4). Pathophysiological parameters were measured for up to 24 hours. The results show that PV resulted in improved oxygenation, decreased shunt fraction, and mortality, with all animals surviving to 24 hours compared to only three of the CV animals. Microscopy confirmed reduced hemorrhage, neutrophilic infiltration, and intra-alveolar edema.

The role of oximes in the treatment of nerve agent poisoning in civilian casualties.

There are important differences between on-target military attacks against relatively well protected Armed Forces and nerve agent attacks initiated by terrorists against a civilian population. In contrast to military personnel, civilians are unlikely to be pre-treated with pyridostigmine and protected by personal protective equipment. Furthermore, the time after exposure when specific therapy can first be administered to civilians is likely to be delayed. Even conservative estimates suggest a delay between exposure and the first administration of atropine/oxime of at least 30 minutes. The organophosphorus nerve agents are related chemically to organophosphorus insecticides and have a similar mechanism of toxicity, but a much higher mammalian acute toxicity, particularly via the dermal route. Nerve agents phosphonylate a serine hydroxyl group in the active site of the enzyme, acetylcholinesterase (AChE), which results in accumulation of acetylcholine and, in turn, causes enhancement and prolongation of cholinergic effects and depolarisation blockade. The rate of spontaneous reactivation of AChE is variable, which partly accounts for differences in acute toxicity between the nerve agents. With soman in particular, an additional reaction occurs known as 'aging'. This consists of monodealkylation of the dialkylphosphonyl enzyme, which is then resistant to spontaneous hydrolysis and reactivation by oximes. Monodealkylation occurs to some extent with all dialkylphosphonylated AChE complexes; however, in general, is only of clinical importance in relation to the treatment of soman poisoning, where it is a very serious problem. With soman, aging occurs so fast that no clinically relevant spontaneous reactivation of AChE occurs before aging has taken place. Hence, recovery of function depends on resynthesis of AChE. As a result, it is important that an oxime is administered as soon after soman exposure as possible so that some reactivation of AChE occurs before all the enzyme becomes aged. Even though aging occurs more slowly and reactivation occurs relatively rapidly in the case of nerve agents other than soman, early oxime administration is still clinically important in patients poisoned with these agents. Experimental studies on the treatment of nerve agent poisoning have to be interpreted with caution. Some studies have used prophylactic protocols, whereas the drugs concerned (atropine, oxime, diazepam) would only be given to a civilian population after exposure. The experimental use of pyridostigmine before nerve agent exposure, although rational, is not of relevance in the civilian context. With the possible exception of the treatment of cyclosarin (GF) and soman poisoning, when HI-6 might be preferred, a review of available experimental evidence suggests that there are no clinically important differences between pralidoxime, obidoxime and HI-6 in the treatment of nerve agent poisoning, if studies employing pre-treatment with pyridostigmine are excluded.

Sulphur mustard injuries of the skin. Pathophysiology and management.

Sulphur mustard is a vesicant (blistering agent), which produces chemical burns with widespread blistering. It was used extensively as a chemical warfare agent in the First World War, and has allegedly been employed in a number of conflicts since then, most recently by Iraq against Iran (1984-1987). The potential further use of mustard in military conflicts and by terrorists remains a significant threat that if realised in practice would result in a large number of casualties with severely incapacitating, partial thickness burns. Such injuries clearly present a huge potential wound care problem. The development and healing of mustard-induced cutaneous injuries has not only been observed in human casualties, but has been studied recently at the microscopic and ultrastructural levels in several animal models. Vesication generally begins on the second day after exposure, and may progress for up to 2 weeks. Wound healing is considerably slower than for a comparable thermal burn, and patients often require extended hospital treatment. The current management strategy is essentially symptomatic and supportive. Recently, two techniques for removing damaged tissue and improving wound healing have been investigated. Mechanical dermabrasion and laser debridement ('lasablation') both produced an increased rate of wound healing in animal models, and may be of benefit in a clinical context.

Ricin poisoning.

Ricin is a naturally occurring toxin derived from the beans of the castor oil plant Ricinus communis. It is considered a potential chemical weapon. Ricin binds to cell surface carbohydrates, is internalised then causes cell death by inhibiting protein synthesis. Oral absorption is poor and absorption through intact skin most unlikely; the most hazardous routes of exposure being inhalation and injection. Features of toxicity mainly reflect damage to cells of the reticuloendothelial system, with fluid and protein loss, bleeding, oedema and impaired cellular defence against endogenous toxins. It has been estimated that in man, the lethal dose by inhalation (breathing in solid or liquid particles) and injection (into muscle or vein) is approximately 5-10 micrograms/kg, that is 350-700 micrograms for a 70 kg adult. Death has ensued within hours of deliberate subcutaneous injection. Management is supportive. Prophylactic immunisation against ricin toxicity is a developing research initiative, although presently not a realistic option in a civilian context.

Abrin poisoning.

Abrin is a toxic protein obtained from the seeds of Abrus precatorius (jequirity bean), which is similar in structure and properties to ricin. Abrin is highly toxic, with an estimated human fatal dose of 0.1-1 microgram/kg, and has caused death after accidental and intentional poisoning. Abrin can be extracted from jequirity beans using a relatively simple and cheap procedure. This satisfies one criterion of a potential chemical warfare agent, although the lack of large scale production of jequirity seeds means that quantity is unavailable for ready mass production of abrin for weapons. This contrasts with the huge cultivation of Ricinus seeds for castor oil production. At the cellular level, abrin inhibits protein synthesis, thereby causing cell death. Many of the features observed in abrin poisoning can be explained by abrin-induced endothelial cell damage, which causes an increase in capillary permeability with consequent fluid and protein leakage and tissue oedema (the so-called vascular leak syndrome). Most reported cases of human poisoning involve the ingestion of jequirity beans, which predominantly cause gastrointestinal toxicity. Management is symptomatic and supportive. Experimental studies have shown that vaccination with abrin toxoid may offer some protection against a subsequent abrin challenge, although such an approach is unlikely to be of benefit in a civilian population that in all probability would be unprotected.

Hybrid modeling for quality by design and PAT-benefits and challenges of applications in biopharmaceutical industry.

This report highlights the drivers, challenges, and enablers of the hybrid modeling applications in biopharmaceutical industry. It is a summary of an expert panel discussion of European academics and industrialists with relevant scientific and engineering backgrounds. Hybrid modeling is viewed in its broader sense, namely as the integration of different knowledge sources in form of parametric and nonparametric models into a hybrid semi-parametric model, for instance the integration of fundamental and data-driven models. A brief description of the current state-of-the-art and industrial uptake of the methodology is provided. The report concludes with a number of recommendations to facilitate further developments and a wider industrial application of this modeling approach. These recommendations are limited to further exploiting the benefits of this methodology within process analytical technology (PAT) applications in biopharmaceutical industry.