Ovine papillomavirus type 3 virus-like particle-based tools for diagnosis and detection of infection.

The design of prophylactic and diagnostic tools specific to animal papillomaviruses is hampered by the difficulties of viral in vitro manipulation and by the scarce availability of dedicated biotechnological tools. This paper reports the production of Ovine Papillomavirus 3 (OaPV3)-based virus-like particles (OaPV3-VLPs) in the baculovirus system and their use to investigate host humoral immune response through the establishment of an indirect ELISA test., Polyclonal sera and monoclonal antibodies were generated against OaPV3-VLPs, and their isotype and reactivity were determined. Additionally, antibodies allowed OaPV3 detection in ovine squamous cell carcinoma (SCC) samples by immunohistochemistry. Results encourage the standardization of OaPV3-specific prophylactic and serological diagnostic tools, and open new perspectives for the study of host-viral interaction and SCC development.

Not seeing the forest for the trees: combination of path integration and landmark cues in human virtual navigation.

Introduction: In order to successfully move from place to place, our brain often combines sensory inputs from various sources by dynamically weighting spatial cues according to their reliability and relevance for a given task. Two of the most important cues in navigation are the spatial arrangement of landmarks in the environment, and the continuous path integration of travelled distances and changes in direction. Several studies have shown that Bayesian integration of cues provides a good explanation for navigation in environments dominated by small numbers of easily identifiable landmarks. However, it remains largely unclear how cues are combined in more complex environments. Methods: To investigate how humans process and combine landmarks and path integration in complex environments, we conducted a series of triangle completion experiments in virtual reality, in which we varied the number of landmarks from an open steppe to a dense forest, thus going beyond the spatially simple environments that have been studied in the past. We analysed spatial behaviour at both the population and individual level with linear regression models and developed a computational model, based on maximum likelihood estimation (MLE), to infer the underlying combination of cues. Results: Overall homing performance was optimal in an environment containing three landmarks arranged around the goal location. With more than three landmarks, individual differences between participants in the use of cues are striking. For some, the addition of landmarks does not worsen their performance, whereas for others it seems to impair their use of landmark information. Discussion: It appears that navigation success in complex environments depends on the ability to identify the correct clearing around the goal location, suggesting that some participants may not be able to see the forest for the trees.

Implementing an electromagnetic tracking navigation system improves the precision of endoscopic transgastric necrosectomy in an ex vivo model.

Endoscopic transgastric necrosectomy is crucial in the management of complications resulting from necrotizing pancreatitis. However, both real-time and visual-spatial information is lacking during the procedure, thereby jeopardizing a precise positioning of the endoscope. We conducted a proof-of-concept study with the aim of overcoming these technical difficulties. For this purpose, a three-dimensional (3D) phantom of a stomach and pancreatic necroses was 3D-printed based on spatial information from individual patient CT scans and subsequently integrated into a silicone torso. An electromagnetic (EM) sensor was adjusted inside the endoscope´s working channel. A software interface enabled real time visualization. The accuracy of this novel assistant system was tested ex vivo by four experienced interventional endoscopists who were supposed to reach seven targets inside the phantom in six different experimental runs of simulated endoscopic transgastric necrosectomy. Supported by endoscopic camera view combined with real-time 3D visualization, all endoscopists reached the targets with a targeting error ranging between 2.6 and 6.5 mm in a maximum of eight minutes. In summary, the EM tracking system might increase efficacy and safety of endoscopic transgastric necrosectomy at the experimental level by enhancing visualization. Yet, a broader feasibility study and further technical improvements are mandatory before aiming at implementation into clinical setting.

Do all Emergency Room Patients With Influenza-like Symptoms Need Blood Cultures? A Retrospective Cohort Study of 2 Annual Influenza Seasons.

In this retrospective cohort study, we evaluated risk factors for bacteremia in emergency department patients presenting with influenza-like symptoms during influenza epidemic seasons. In patients without fever, chronic heart or chronic liver disease, blood culture collection might be omitted.

Efficiency and safety of nasal positive airway pressure systems during endoscopic procedures in high-risk patients: Endo-Breath study.

Background and study aims Sedation of high-risk patients is a relevant issue in interventional endoscopy. This is especially because standard oximetric monitors display only hypoxia and not the preceding hypercapnia. Therefore, the question arises whether use of a nasal positive airway pressure (nPAP) system can decrease the rate of sedation-associated events. Patients and methods A randomized, prospective trial was conducted at University Hospital Ulm, including 98 consecutive patients, identified as high-risk (American Society of Anesthesiologists physical status ≥3) and scheduled for prolonged (>15 minutes) endoscopic procedures. Patients underwent 1:1 randomization to two groups: interventional (nPAP-Mask) and control (conventional oxygen supplementation). Levels of CO 2 were measured noninvasively by transcutaneous capnometry device. The primary outcome was incidence of hypoxia (SpO 2 <90% over 10 seconds) and incidence of severe hypoxia was incidence of SpO 2 <80% over 10 seconds. One of our secondary objectives was to determine if the nPAP-Mask could result in significant CO 2 retention among high-risk patients. Results Data analysis showed lower incidence of hypoxia in the interventional group (10/47 vs. 31/251) P <0.05. Episodes of severe hypoxia (SpO 2 <80% over 10 seconds) were more frequent in the control group (8/51) compared with the intervention group (2/47) P <0.05. There was no significant difference in ΔCO 2 levels in the interventional vs. control group (-6.01±7.66 vs. -7.35±8.59 mm Hg). Conclusions In high-risk patients use of a nasal positive airway pressure system could significantly lower risk of hypoxia, especially in prolonged procedures. The nPAP-Mask does not induce CO 2 retention when compared with conventional oxygen supplementation.

[Metastasis in the periocular region]. / Metastase in der periokulären Region.

Orbital and periocular metastatic tumors used to be considered very rare; however, with the constant updating of drugs and detection methods for cancer treatment, new chemotherapies and radiation treatments are being used. The life expectancy of cancer patients has become longer and periocular metastases are becoming easier to detect. Our knowledge of this rare disease of metastases also needs to be updated. This article reviews the incidence, symptomatic presentation, clinical features, diagnostic approaches and current treatment of metastatic tumors of the orbit and ocular adnexa in these patients.

Accuracy between prehospital and hospital diagnosis in helicopter emergency medical services and its consequences for trauma care.

PURPOSE: For optimal prehospital trauma care, it is essential to adequately recognize potential life-threatening injuries in order to correctly triage patients and to initiate life-saving measures. The aim of the present study was to determine the accuracy of prehospital diagnoses suspected by helicopter emergency medical services (HEMS). METHODS: This retrospective multicenter study included patients from the Swiss Trauma Registry with ISS ≥ 16 or AIS head ≥ 3 transported by Switzerland's largest HEMS and subsequently admitted to one of twelve Swiss trauma centers from 01/2020 to 12/2020. The primary outcome was the comparison of injuries suspected prehospital with the final diagnoses obtained at the hospital using the abbreviated injury scale (AIS) per body region. As secondary outcomes, prehospital interventions were compared to corresponding relevant diagnoses. RESULTS: Relevant head trauma was the most commonly injured body region and was identified in 96.3% (95% CI: 92.1%; 98.6%) of the cases prehospital. Relevant injuries to the chest, abdomen, and pelvis were also common but less often identified prehospital [62.7% (95% CI: 54.2%; 70.6%), 45.5% (95% CI: 30.4%; 61.2%), and 61.5% (95% CI: 44.6%; 76.6%)]. Overall, 7 of 95 (7.4%) patients with pneumothorax received a chest decompression and in 22 of 39 (56.4%) patients with an instable pelvic fracture a pelvic binder was applied prehospital. CONCLUSION: Approximately half of severe chest, abdominal, and pelvic diagnoses made in hospital went undetected in the challenging prehospital environment. This underlines the difficult circumstances faced by the rescue teams. Potentially life-saving interventions such as prehospital chest decompression and increased use of a pelvic binder were identified as potential improvements to prehospital care.

[Clinical approach for solid intraocular metastases]. / Klinisches Vorgehen bei soliden intraokulären Metastasen.

BACKGROUND: Intraocular metastases arising from solid tumors are found in approximately 2% of patients with metastatic tumor diseases and are therefore more frequent than originally assumed. They often affect the uvea and are associated with a poor prognosis. Due to the difficult diagnosis and an inconsistent treatment regimen, ophthalmologists have a special responsibility here. OBJECTIVE: This article gives a summary of the various types of intraocular metastases with respect to clinical features, diagnostics, treatment and prognosis as well as recommendations for follow-up care. METHODS: A selective literature search was carried out on the topic of intraocular metastases using PubMed and Google Scholar. RESULTS: Intraocular metastases most frequently affect the uvea, specifically the choroid. In most cases the underlying disease is breast or lung cancer, but other rarer primary tumors have also been reported in the literature. Metastatic lesions can show very different morphological manifestations but can be distinguished based on the corresponding structure of manifestation in the eye and with the aid of targeted staging, thus providing valid information on the type of primary tumor. The treatment is partly experimental and usually depends on the primary tumor and leading symptoms of the patient. A differentiation between a curative or palliative treatment situation must always be made. CONCLUSION: Intraocular metastases are the most frequent intraocular tumor and are usually associated with a poor prognosis. Accurate diagnostics for finding the treatment as well as interdisciplinary collaboration and the presentation of the patient on the tumor board are essential.

Who was at risk of trauma-related injuries during the COVID-19 pandemic? A retrospective study from a level 1 trauma centre in Switzerland.

INTRODUCTION: During the first wave of the COVID-19 pandemic, increasingly strict restrictions were imposed on the activities of the Swiss population, with a peak from 21 March to 27 April 2020. Changes in trauma patterns during the pandemic and the lockdown have been described in various studies around the world, and highlight some particularly exposed groups of people. The objective of this study was to assess changes in trauma-related presentations to the emergency department (ED) during the first wave of the COVID-19 pandemic, as compared to the same period in the previous year, with a particular focus on vulnerable populations. MATERIALS AND METHODS: All trauma-related admissions to our ED in the first half of 2019 and 2020 were included. Patient demographics, trauma mechanism, affected body region, injury severity and discharge type were extracted from our hospital information system. Trauma subpopulations, such as interpersonal violence, self-inflicted trauma, geriatric trauma and sports-related trauma were analysed. RESULTS: A total of 5839 ED presentations were included in our study, of which 39.9% were female. Median age was 40 years (interquartile range: 27-60). In comparison to 2019, there was a 15.5% decrease in trauma-related ED presentations in the first half of 2020. This decrease was particularly marked in the 2-month March/April period, with a drop of 36.8%. In 2020, there was a reduction in injuries caused by falls of less than 3 metres or by mechanical force. There was a marked decrease in sports-related trauma and an increase in injuries related to pedal cycles. Geriatric trauma, self-harm and assault-related injuries remained stable. CONCLUSION: This study described changes in trauma patterns and highlighted populations at risk of trauma during the pandemic in Switzerland in the context of previous international studies.These results may contribute to resource management in a future pandemic.

[Staging and systemic treatment of ocular and periocular metastases]. / Staging und Systemtherapie bei okulären und periokulären Metastasen.

Metastases of malignant diseases are the most frequent tumors diagnosed in the human eye. They occur in approximately 5-10% of patients with solid tumors during the course of the disease. Their frequency is particularly high in patients with breast and lung cancer. Many highly sensitive periorbital tissues can be affected by the localization of the metastatic lesions and pose a number of clinical challenges. The main goal of the therapy of ocular metastases consists of the control of tumor growth (including the control of other possible manifestations throughout the body), the preservation of the affected eye and the minimization of potential iatrogenic damage to adjacent tissues. Overall, the purpose of this strategy is also to maintain the quality of life and especially the eyes and vision of the patient. Furthermore, pain should be avoided or at least alleviated. Of special importance is the differentiation between a curative or palliative situation. Patients with ocular metastases usually undergo systemic treatment appropriate for the underlying tumor entity, which is often accompanied by concomitant or sequential radiotherapy. In addition to classical chemotherapy, targeted treatment, treatment with monoclonal antibodies and antibody-drug conjugates as well as immunotherapy with checkpoint antibodies are currently available for many cancer types. This review article gives an overview of the currently available treatment options for patients with ocular metastases of solid tumors.

Pre-Stroke Antihypertensive Therapy Affects Stroke Severity and 3-Month Outcome of Ischemic MCA-Territory Stroke.

OBJECTIVES: Whether different antihypertensive drug classes in high blood pressure (HBP) pre-stroke treatment affect dynamic cerebral autoregulation (dCA), stroke severity, and outcome. METHODS: Among 337 consecutive ischemic stroke patients (female 102; median age 71 years [interquartile range, [IQR 60; 78]; NIHSS median 3 [IQR 1; 6]) with assessment of dCA, 183 exhibited the diagnosis of HBP. dCA parameters' gain and phase were determined by transfer function analysis of spontaneous oscillations of blood pressure and cerebral blood flow velocity. RESULTS: Patients used beta-blockers (n = 76), calcium channel blockers (60), diuretics (77), angiotensin-converting enzyme inhibitors (59), or angiotensin-1 receptor blockers (79), mostly in various combinations of two or three drug classes. dCA parameters did not differ between the non-HBP and the different HBP medication groups. Multinomial ordinal logistic regression models revealed that the use of diuretics decreased the likelihood of a less severe stroke (odds ratio 0.691, 95% CI 0.493; 0.972; p = 0.01) and that beta-blockers decreased the likelihood of a better modified Rankin score at 3 months (odds ratio 0.981, 95% CI 0.970; 0.992; p = 0.009). Other independent factors associated with stroke outcome were penumbra and infarct volume, treatment with mechanical thrombectomy, and the initial National Institute of Health Stroke Scale score. INTERPRETATION: In this cohort of ischemic minor to moderate stroke patients, pre-stroke antihypertensive treatment with diuretics was associated with a more severe neurological deficit on admission and pre-stroke treatment with beta-blockers with a poorer 3-month outcome. The antihypertensive drug class used pre-stroke did not impact dCA.

Ecological variation in adult social play reveals a hidden cost of motherhood for wild chimpanzees.

Though common among humans, social play by adults is an uncommon occurrence in most animals, even between parents and offspring.1,2,3 The most common explanation for why adult play is so rare is that its function and benefits are largely limited to development, so that social play has little value later in life.3,4,5,6 Here, we draw from 10 years of behavioral data collected by the Kibale Chimpanzee Project to consider an alternative hypothesis: that despite its benefits, adult play in non-humans is ecologically constrained by energy shortage or time limitations. We further hypothesized that, since they may be the only available partners for their young offspring, mother chimpanzees pay greater costs of play than other adults. Our analysis of nearly 4,000 adult play bouts revealed that adult chimpanzees played both among themselves and with immature partners. Social play was infrequent when diet quality was low but increased with the proportion of high-quality fruits in the diet. This suggests that adults engage in play facultatively when they have more energy and/or time to do so. However, when diet quality was low and most adult play fell to near zero, play persisted between mothers and offspring. Increased use of play by adult chimpanzees during periods of resource abundance suggests that play retains value as a social currency beyond development but that its costs constrain its use. At the same time, when ecological conditions constrain opportunities for young to play, play by mothers fills a critical role to promote healthy offspring development.

Conformational Space of the Translocation Domain of Botulinum Toxin: Atomistic Modeling and Mesoscopic Description of the Coiled-Coil Helix Bundle.

The toxicity of botulinum multi-domain neurotoxins (BoNTs) arises from a sequence of molecular events, in which the translocation of the catalytic domain through the membrane of a neurotransmitter vesicle plays a key role. A recent structural study of the translocation domain of BoNTs suggests that the interaction with the membrane is driven by the transition of an α helical switch towards a ß hairpin. Atomistic simulations in conjunction with the mesoscopic Twister model are used to investigate the consequences of this proposition for the toxin-membrane interaction. The conformational mobilities of the domain, as well as the effect of the membrane, implicitly examined by comparing water and water-ethanol solvents, lead to the conclusion that the transition of the switch modifies the internal dynamics and the effect of membrane hydrophobicity on the whole protein. The central two α helices, helix 1 and helix 2, forming two coiled-coil motifs, are analyzed using the Twister model, in which the initial deformation of the membrane by the protein is caused by the presence of local torques arising from asymmetric positions of hydrophobic residues. Different torque distributions are observed depending on the switch conformations and permit an origin for the mechanism opening the membrane to be proposed.

Interface and Morphology Engineered Amorphous Si for Ultrafast Electrochemical Lithium Storage.

Ultrafast high-capacity lithium-ion batteries are extremely desirable for portable electronic devices, where Si is the most promising alternative to the conventional graphite anode due to its very high theoretical capacity. However, the low electronic conductivity and poor Li-diffusivity limit its rate capability. Moreover, high volume expansion/contraction upon Li-intake/uptake causes severe pulverization of the electrode, leading to drastic capacity fading. Here, interface and morphology-engineered amorphous Si matrix is being reported utilizing a few-layer vertical graphene (VG) buffer layer to retain high capacity at both slow and fast (dis)charging rates. The flexible mechanical support of VG due to the van-der-Waals interaction between the graphene layers, the weak adhesion between Si and graphene, and the highly porous geometry mitigated stress, while the three-dimensional mass loading enhanced specific capacity. Additionally, the high electronic conductivity of VG boosted rate-capability, resulting in a reversible gravimetric capacity of ≈1270 mAh g-1 (areal capacity of ≈37 µAh cm-2 ) even after 100 cycles at an ultrafast cycling rate of 20C, which provides a fascinating way for conductivity and stress management to obtain high-performance storage devices.

Inter-epitope spacer variation within polytopic L2-based human papillomavirus antigens affects immunogenicity.

The human papillomavirus minor capsid protein L2 is being extensively explored in pre-clinical studies as an attractive vaccine antigen capable of inducing broad-spectrum prophylactic antibody responses. Recently, we have developed two HPV vaccine antigens - PANHPVAX and CUT-PANHPVAX- both based on heptameric nanoparticle antigens displaying polytopes of the L2 major cross-neutralizing epitopes of eight mucosal and twelve cutaneous HPV types, respectively. Prompted by the variable neutralizing antibody responses against some of the HPV types targeted by the antigens observed in previous studies, here we investigated the influence on immunogenicity of six distinct glycine-proline spacers inserted upstream to a specific L2 epitope. We show that spacer variants differentially influence antigen immunogenicity in a mouse model, with the antigen constructs M8merV6 and C12merV6 displaying a superior ability in the induction of neutralizing antibodies as determined by pseudovirus-based neutralization assays (PBNAs). L2-peptide enzyme-linked immunosorbent assay (ELISA) assessments determined the total anti-L2 antibody level for each antigen variant, showing for the majority of sera a correlation with their repective neutralizing antibody level. Surface Plasmon Resonance revealed that L2 epitope-specific, neutralizing monoclonal antibodies (mAbs) display distinct avidities to different antigen spacer variants. Furthermore, mAb affinity toward individual spacer variants was well correlated with their neutralizing antibody induction capacity, indicating that the mAb affinity assay predicts L2-based antigen immunogenicity. These observations provide insights on the development and optimization of L2-based HPV vaccines.

Emergency department utilisation and treatment for trauma-related presentations of adolescents aged 16-18: a retrospective cross-sectional study.

BACKGROUND: A recent study conducted at our tertiary hospital emergency department (ED) reviewed ED consultations and found that adolescents aged 16-18 years present significantly more often for trauma and psychiatric problems than adults over 18 years. Accidental injuries are one of the greatest health risks for children and adolescents. In view of the increased vulnerability of the adolescent population, this study aimed to further analyse trauma-related presentations in adolescents. METHODS: We conducted a single-centre, retrospective, cross-sectional study of all adolescent trauma patients aged 16 to 18 years presenting to the adult ED at the University Hospital (Inselspital) in Bern, Switzerland, from January 2013 to July 2017. We analysed presentation data as well as inpatient treatment and cost-related data. Data of female and male patients were compared by univariable analysis. A comparison group was formed consisting of 200 randomly chosen patients aged 19-25 years old with the same presentation characteristics. Predictive factors for surgical treatment were obtained by multivariable analysis. RESULTS: The study population included a total of 1,626 adolescent patients aged 16-18 years. The predominant causes for ED presentation were consistent within case and comparison groups for sex and age and were sports accidents, falls and violence. Male patients were more likely to need surgical treatment (OR 1.8 [95% CI: 1.2-2.5], p = 0.001) and consequently inpatient treatment (OR 1.5 [95% CI: 1.1-2.1], p = 0.01), associated with higher costs (median 792 Swiss francs [IQR: 491-1,598]). Other independent risk factors for surgical treatment were violence-related visits (OR 2.1 [95% CI: 1.3-3.5, p = 0.004]) and trauma to the upper extremities (OR 2.02 [95% CI: 1.5-2.8], p < 0.001). Night shift (OR 0.56 [95% CI: 0.37-0.86], 0.008) and walk-in consultations (OR 0.3 [95% CI: 0.2; 0.4, < 0.001] were preventive factors for surgical treatment. CONCLUSIONS: Male adolescents account for the majority of emergency visits and appear to be at higher risk for accidents as well as for surgical treatment and/or inpatient admission due to sports accidents or injuries from violence. We suggest that further preventive measures and recommendations should be implemented and that these should focus on sport activities and injuries from violence.

Computation of X-ray and Neutron Scattering Patterns to Benchmark Atomistic Simulations against Experiments.

Molecular Dynamics simulations study material structure and dynamics at the atomic level. X-ray and neutron scattering experiments probe exactly the same time- and length scales as the simulations. In order to benchmark simulations against measured scattering data, a program is required that computes scattering patterns from simulations with good single-core performance and support for parallelization. In this work, the existing program Sassena is used as a potent solution to this requirement for a range of scattering methods, covering pico- to nanosecond dynamics, as well as the structure from some Ångströms to hundreds of nanometers. In the case of nanometer-level structures, the finite size of the simulation box, which is referred to as the finite size effect, has to be factored into the computations for which a method is described and implemented into Sassena. Additionally, the single-core and parallelization performance of Sassena is investigated, and several improvements are introduced.