Management of diabetic foot ulcers (DFUs) presents challenges to even the most experienced wound care providers. Because of the chronic, non-healing nature of many DFUs, advances in the treatment and care of this disease process are particularly relevant. This case study aims to report the efficacy of the application of dehydrated amniotic membrane allograft (DAMA) to a diabetic foot ulcer. The patient in this study is a 44-year-old male who presented with an aggressive infection on his right foot, which resulted in an open wound of 18 months duration. This patient received weekly applications of dual-layer DAMA over seven weeks. Upon examination at the initial application, the wound was classified as a Wagner grade 3 with necrosis of the underlying muscle. Upon inspection at the final visit, the wound was closed entirely. The results that were shown include improvements in the size, depth, edges, necrotic tissue amount, and epithelization of the wound. This case study demonstrates that the ap-plication of DAMA has the potential to augment the body’s natural DFU healing response; however, future nonrandomized and randomized controlled trials are needed to establish its efficacy further.

The use of chemical pesticides in agriculture contributes to soil, water and air pollution, biodiversity loss and can harm non-target species. The European Commission has already established a Harmonized Risk Indicator to quantify the progress in reducing the risks linked to pesticides. Therefore, there is an increasing need to promote biopesticides or so-called low-risk pesticides (LRP). Extract from Melaleuca alternifolia – tea tree oil (TTO) is known for its antiseptic, antimicrobial, antiviral, antifungal, and anti-inflammatory properties. Tea tree oil has been extensively studied in pest management as well as in the pharmaceutical and cosmetic industry and there are already products based on its active substances on the market. This review focuses on the overall evaluation of tea tree oil in terms of effectiveness and safety as a biopesticide for the first time. The collected data can be an added value for further evaluation of tea tree oil in terms of the authorization extension as a fungicide in 2026.

Background. Ovarian cysts are common in premenopausal women but can present with vague, non-specific symptoms, making discovery more challenging. Most are benign and resolve spontaneously; however, they can present, as in this case, as ovarian torsions, which is a gynecological emergency. Case presentation. A twenty-year-old female had presented over 3–4 times per year for the last 6 years to her primary doctor citing intermittent abdominal pain, irregular menstruation, dyspnea, and an enlarging abdomen circumference. The doctor stated, she was “just fat” and could, benefit from a “special camp to lose weight”, so she stopped mentioning her concerns. Upon presenting to the emergency department with acute onset abdominal pain, a computed tomography scan showed a large cyst lesion filling the abdominal and pelvic cavity. Its origin appeared to be from the left adnexa. Surgery was performed, and an acute ovarian torsion caused by a 36 cm craniocaudal left ovarian cyst was found and removed along with the left fallopian tube and 16 L of fluid. Conclusions. The value of respecting the “third presentation” rule indicates to health care providers that any patient who presents with any /or other symptoms or complaint needs to be thoroughly investigated. In this case the patient presented recurring pelvic/abdominal concerns, irregular menstruation, which warranted further investigation to safeguard fertility and prevent errors of omission. It is important to consider the differentials and be aware of vague symptoms that may lead to early recognition and effective management to prevent adverse consequences, complications, or even death.

Mast cells (MCs) play a crucial role during infections with Leishmania, that is transmitted through the bite of an infected sand fly that injects saliva together with the parasite. Sand fly saliva is a complex fluid that modulates the host immune response. In addition, hormonal factors modulate the host immune response, impacting the susceptibility to infections. Thus, to assess the impact of androgens and salivary proteins of sand fly vectors on the mast cell (MC) response to Leishmania infections, we infected orchiectomized male mice with the parasite in the presence or absence of sand fly salivary proteins and analyzed the inflammatory response of MCs. Our results showed a differential MC response to the parasite and to vector salivary proteins in mice deprived of gonadal hormones, as compared to sham-operated mice. Orchidectomy induced a different pattern of activation in MC of animals infected with Leishmania and vector-salivary proteins. Our results show that during Leishmania infection, androgens modulate the innate immunity response against the parasite and salivary proteins of the sand fly vector.

The research is based on the inspection performed in June 2002 for carrying out a research program for the eradication of a termite infestation due a desertic species in the area of the Saint Catherine Holy Monastery at Mount Sinai - Egypt. The paper describes the application of the registered European bait system SentritechTM and the trend of eradication during the first year. The application of bait system blocked the termite infestation inside the Katholikon (Main church) and in the surrounding after 6 months. Nevertheless, the infestation restarted and even increased again in the surrounding of the main church. An explanation of this surprising event is attempted in this paper.

(1) Background: Non-surgical endodontic treatment has been repeatedly shown to be clinically successful, however, clinical data are scarce. This practice-based retrospective clinical study aimed to investigate endodontic outcome over 40 years and to identify relevant factors from clinical protocols. (2) Methods: Two experienced dental practitioners in two different private dental practices treated 174 patients with 243 teeth from 1969 to 1993. After obturation, either a new restoration (amalgam, resin composite, glass-ionomer cement), or re-cementation of pre-existing prosthetic restorations or its renewal followed. Metal posts (operator A) or screws (operator B) were inserted when indicated. The primary outcome (tooth survival) was achieved when the endodontically treated tooth was in situ, painless and in full function. Secondary outcome was to investigate the impact of potential prognostic factors on survival rates. (3) Results: Overall mean 40-years survival was 56.1% of all treated teeth after 40 years of clinical service resulting in an annual failure rate of 1.1%. Most investigated clinical factors (Jaw, tooth position, number of intracanal dressings, post/screw placement, sex) had no significant influence on survival. Among postendodontic restorations, resin composite was advantageous. (4) Conclusions: Even with materials and techniques from the 1970’s and 1980’s, successful root canal treatment was achievable. Except postendodontic restorations, most of the evaluated factors had no significant influence on clinical long-term survival of root-canal treated teeth.

Background/Aim: There is continuing interest in engineering esthetic labial archwires. The aim of this study was to coat nickel-titanium (NiTi) and beta-titanium (β-Ti), also known as titanium molybdenum (TMA), archwires by plasma electrolytic oxidation (PEO) and to analyze the characteristics of the PEO-surfaces. Materials and Methods: PEO-coatings were generated on 0.014-inch NiTi and 0.19x0.25-inch β-Ti archwires. The surfaces were analyzed by scanning electron microscopy and stereomicroscopy. Cytocombability testing was performed with ceramized and untreated samples according to EN ISO 10993-5 in XTT-, BrdU- and LDH-assays. The direct cell impact was analyzed using LIVE-/DEAD-staining. In addition, the archwires were inserted in an orthodontic model and photographs were taken before and after insertion. Results: The PEO coatings were 15 to 20 µm thick and esthetically pleasing. The cytocompatibility analysis revealed good cytocompatibility results for both ceramized NiTi and β-Ti archwires. In the direct cell tests, the ceramized samples showed improved compatibility as compared to those of uncoated samples. However, bending of the archwires resulted in loss of the PEO-surfaces. Nevertheless, it was possible to insert the β-Ti PEO-coated archwire in an orthodontic model without loss of the PEO-ceramic. Conclusion: PEO is a promising technique for the generation of esthetic orthodontic archwires. Since the PEO-coating does not resist bending, its clinical use seems to be limited so far to orthodontic techniques using straight or pre-bended archwires.

Mapping short-term wetland vegetation and water storage changes is valuable for monitoring the biogeochemical processes of wetland systems. Old Woman Creek National Estuarine Research Reserve is a dynamic freshwater estuary that experiences intermittent changes in water level over the course of a year. Small unmanned aerial systems (sUAS) are useful tools in monitoring changes as they are rapidly deployed, repeatable, and high-resolution. In this study, commercial quadcopters were paired with a red/green/near-infrared MAPIR Survey 3W camera to produce normalized difference vegetation index (NDVI) and normalized difference water index (NDWI) maps to observe short-term changes at OWC. Orthomosaics were produced for flights on 8 days throughout 2018 and early 2019. The orthomosaics were calibrated to bottom-of-atmosphere reflectance using the Empirical Line Correction method and NDVI and NDWI maps were created. The NDVI pixel values were used to generate maps of vegetation extent showing density changes over time. Identifying dominant vegetation in these maps allowed for the application of the National Estuarine Reserve System (NERRS) Classification Codes to zones of interest. NDWI provided water extent at different water levels and when paired with LiDAR and bathymetric data yielded water volume and residence time estimates. The produced maps contribute to the overall understanding of habitats affected by water inundation variations.

Among non-conventional yeasts of industrial interest, the dimorphic oleaginous yeast Yarrowia lipolytica appears as one of the most attractive for a large range of white biotechnology applications, from heterologous proteins secretion to cell factories process development. The past, present and potential applications of wild type, traditionally improved or genetically modified Yarrowia lipolytica strains will be resumed, together with the wide array of molecular tools now available to genetically engineer and metabolically remodel this yeast. The present review will also provide a detailed description of Yarrowia lipolytica strains and highlight the natural biodiversity of this yeast, a subject little touched upon in most previous reviews. This work intends to fill this gap by retracing the genealogy of the main Yarrowia lipolytica strains of industrial interest, by illustrating the search for new genetic backgrounds and by providing data about the main publicly available strains in yeast collections worldwide. At last, it will focus on exemplifying how advances in engineering tools can leverage a better biotechnological exploitation of the natural biodiversity of Yarrowia lipolytica and of other yeasts from the Yarrowia clade.

The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are already approved by worldwide regulatory bodies including the FDA, using the ZINC database. Screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. A top lead from each target group was further subjected to molecular dynamics simulation (MDS) using the Desmond module to validate the efficacy of the screening pipeline. All of the simulated hit-target complexes were predicted to strongly interact and with highly stable binding. Thus, we have identified a number of approved and investigational drugs with high likelihood of inhibiting a variety of key SARS-CoV-2 proteins. Follow-up studies will continue to identify inhibitors suitable for combination therapy based on drug-drug synergy to thwart resistance. In addition, the screening hits that we have identified provide excellent probes for understanding the binding properties of the active sites of all seven targets, further enabling us to derive consensus molecules through computer-aided drug design (CADD). While infections are expanding at a rampant pace, it must be recognized that resistance will grow commensurately through either genetic shift and/or genetic drift to all small molecule drugs identified. Vaccines should provide a more permanent solution through prevention, but resistivity is still a possible scenario. Nevertheless, a persistent multi-target drug development program is essential to curb this ongoing pandemic and to keep reemergence in check.

In thermal power plants equipped with air-cooled condensers, axial cooling fans operate under the influence of ambient flow fields. Under inlet cross-flow conditions, the resultant asymmetric flow field is known to introduce additional harmonic forces to the fan blades. This effect has previously been studied only numerically or using blade mounted strain gauges. For this study, Laser Scanning Vibrometry was used to assess fan blade vibration under inlet cross-flow conditions in an adapted fan test rig inside a wind tunnel test section. Two co-rotating laser beams scanned a low pressure axial fan, resulting in spectral, phase resolved surface vibration patterns of the fan blades. Two distinct operating points were examined, with and without inlet cross-flow influence. While almost identical fan vibration patterns were found for both reference operating points, overall blade vibration increased by 100% at low fan flow rate due to cross-flow, and by 20% at high fan flow rate. While numerically predicted natural frequency modes could be confirmed from experimental data as minor peaks in the vibration amplitude spectrum, they were not excited significantly by cross-flow. Instead, primarily higher rotation rate harmonics were amplified, i.a. a synchronous blade tip flapping was strongly excited at the blade pass frequency.

This review provides a comprehensive and updated information on chalcones, presenting their sources, methods of identification and properties putting emphasis on applications in agricultural industry. Vast exploitation of synthetic pesticides led to the weed and pest resistance issue, causing economic loss but more importantly health risk due to pesticide overuse. Because one of the aim of the European Green Deal 2030 is the Farm to Fork strategy which targets on reducing by 50% the use of chemical pesticides by 2030, and push towards natural pesticides which are more environmentally friendly and restore natural resources, chalcones and their derivatives seem to fit perfectly. They have herbicidal, fungicidal, bactericidal and antiviral properties. Moreover, chalcones are naturally occurring substances, known for their favorable health effect for years, working on many areas. This review is complementary to the previous ones describing chalcones use in agriculture, updates them but additionally shows methods of detection.

Lithium titanates are used in various applications, such as anode materials for lithium intercalation (Li4Ti5O12) or breeding materials in fusion reactors (Li2TiO3). Here, we report the formation of nano-crystalline lithium titanates by a mechanochemical approach and present a deeper insight into their structural characteristics by PXRD and solid-state NMR spectroscopy. The compounds were synthesized in a high energy planetary ball mill with varying milling parameters and different grinding tools. NaCl type Li2TiO3 (α-Li2TiO3) was formed by dry milling of lithium hydroxide with titania (rutile or anatase) and by a milling induced structure transformation of monoclinic β Li2TiO3 or spinel type Li4Ti5O12. Heating of mechanochemical prepared α Li2TiO3 induces a phase transformation to the monoclinic phase similar to hydrothermal reaction products, but a higher thermal stability was observed for the mechanochemical formed product. Microstructure and crystallographic structure were characterized by PXRD via Rietveld analysis. Detailed phase analysis shows the formation of the cubic phase from the various educts. A set of two lattice parameters for α Li2TiO3 was refined, depending on the presence of OH- during the milling process. An average crystallite size of less than 15 nm was observed for the mechanochemical generated products. The local Li environment detected by 6Li SPE MAS NMR revealed Li defects in the form of tetrahedral instead of octahedral site occupation. Subsequent adjustment of the structural model for Rietveld refinement leads to better fits, supporting this interpretation.

In this paper, we study the asymptotic behavior of the sequential empirical process and the sequential empirical copula process, both constructed from residuals of multivariate stochastic volatility models. Applications for the detection of structural changes and specification tests of the distribution of innovations are discussed. It is also shown that if the stochastic volatility matrices are diagonal, which is the case if the univariate time series are estimated separately instead of being jointly estimated, then the empirical copula process behaves as if the innovations were observed; a remarkable property. As a by-product, one also obtains the asymptotic behavior of rank-based measures of dependence applied to residuals of these time series models.

Floral meristems are dynamic systems that generate floral organ primordia at their flanks and, in most species, terminate while giving rise to the gynoecium primordia. However, we find species with floral meristems that generate additional ring meristems repeatedly throughout angiosperm history. Ring meristems produce only stamen primordia, resulting in polystemous flowers (having stamen numbers more than double that of petals or sepals), and act independently of the floral meristem activity. Most of our knowledge on floral meristem regulation is derived from molecular genetic studies of Arabidopsis thaliana, a species with a fixed number of floral organs and as such of only limited value to understand ring meristem function, regulation, and ecological value. This review provides an overview of the main molecular players regulating floral meristem activity in A. thaliana, and summarizes our knowledge of ring primordia morphology and occurrence in dicots. Our work provides a first step towards understanding the significance and molecular genetics of ring meristem regulation and evolution.

Appropriate animal models of human diseases are a cornerstone in the advancement of science and medicine. To create animal models of neuropsychiatric and neurobehavioral diseases such as ASD necessitates the development of sufficient neurobehavioral measuring tools to translate human behavior to expected measurable behavioral features in animals. Indeed, at least in rodents, adequate neurobehavioral and neurological tests have been developed. Since ASD is characterized by a number of specific behavioral trends with significant severity, animal models of autistic-like behavior have to demonstrate the specific characteristic features, namely impaired social interactions, and communication, restricted, repetitive behavioral patterns with association to several additional impairments such as somatosensory, motor and memory impairments. Thus, an appropriate model must show behavioral impairment of a minimal number of neurobehavioral characteristics using an adequate number of behavioral tests. The proper animal models enable the study of ASD like-behavior from the etiologic, pathogenetic and therapeutic aspects. From the etiologic aspects, models have been developed by the use of immunogenic substances like polyinosinic-polycytidylic acid (PolyIC), Lipopolysaccharide (LPS) and propionic acid or other well-documented immunogens or pathogens, like mycobacterium tuberculosis. Another approach is the use of chemicals like valproic acid, Polychlorinated biphenyls (PCBs), organophosphate pesticides - chlorpyrifos (CPF) and others. These substances were administered either prenatally, generally after the period of major organogenesis, or, especially in rodents, during the early postnatal life. In addition, using modern genetic manipulation methods, genetic models have been created of almost all human genetic diseases that are manifested by autistic like behavior (i.e. fragile X, Rett syndrome, SHANK gene mutation Neuroligin genes and others). Ideally, we should not only evaluate the different behavioral modes affected by the ASD-like behavior but also assess the severity of the behavioral deviations by an appropriate scoring system, as applied to humans.

This work mainly aims to identify and understand the factors influencing the switching of transportation modes among higher-education students in Joinville, Brazil when traveling to universities. Furthermore, this study evaluates the possibility of switching from individual vehicles to other modes of transport (i.e., bus, bicycle, and walking) by employing a multinomial logit model. The results indicate that students would be interested in switching from individual motor vehicles to other options. The scenarios for switching to buses presented the highest switching probability. The bus cost was the most important factor for switching. Meanwhile, the parking space reduction does not affect the student's choice, indicating that restricting available spaces should not be an isolated measure for decreasing the car mode attractiveness. Finally, the transport mode switch would occur only if alternative modes to the car or their infrastructure are improved; otherwise, students maintain their usual choices.

This study investigates the impact of geomagnetic storms that occurred on June 8, 22-23, and 25, 2015, on the ionosphere in the low-latitude and equatorial regions of Brazil. By examining various data sources, such as solar wind parameters from the ACE satellite, GPS vertical total electron content (VTEC), magnetometer data, and the SAMI2 model, we aimed to simulate the effects of storms on the ionosphere in these regions. Two methods were employed to separate DP2 and Disturbance dynamo (Ddyn) from the ionospheric disturbance current (Diono). Our analysis revealed a positive (negative) ionospheric storm in the VTEC during the main phase (recovery) of the June 22-23 and 25 storms. This observation can be attributed to the combined impact of the eastward prompt penetration of the magnetospheric convection electric field (westward disturbance dynamo electric field) and changes in the storm-time thermospheric [O]/[N_2] ratio based on the GUVI satellite imagery. Notably, the westward disturbance dynamo exhibited a significant amplitude on June 23 in Belem. The amplitude of the D_dyn at Belem (dip lat: - 0.47˚) was greater than that at Alta Floresta (dip lat: - 3.75˚) due to intensified cowling conductivity in Belem. Furthermore, we found that the SAMI2 model provided more accurate results when we replaced the default ExB drift with the vertical drift calculated from the ground-based magnetometer, enabling us to simulate the effect of the westward DDEF on VTEC during daytime.

There has been growing interest in using permanent magnet synchronous motors (PMSMs) for pumping applications to improve energy efficiency. One promising approach for powering these motors in variable speed applications is using modular multilevel cascaded converters based on a Triple-Star Bridge Cell (M3C) due to their inherent fault tolerance capability. However, M3C converters require a more complex control system than simpler converters. For instance, A basic M3C control system for power transmission requires seventeen (17) PI controllers, whose adjustment depends on the M3C’s dynamical model parameters’ value knowledge needing extensive and time-consuming testing to obtain them. To solve this control system issue, we propose an adaptive M3C control system for variable speed drives powering multiple PMSM-driven centrifugal pumps that reduces the number of controllers to six (6). Furthermore, the proposal does not require knowledge of the converter, motor, or load parameters, making it more practical and versatile. The proposal introduces an ad-hoc hybrid passivity-based model reference adaptive controller in cascade with a passivity-based control. It has been validated through theoretical stability proof and comparative simulation results with a basic control system under normal and fault operations. As a result, the proposal effectively follows the required rotor speed while enhancing performance by decreasing the current consumption and recovering from a 10% input phase imbalance, a cell short circuit, and an open cell.

Postural deficits such as hyperlordosis (hollow back) or hyperkyphosis (hunchback) are relevant health issues. Diagnoses depend on the experience of the examiner and are therefore often subjective and prone to errors. Machine learning (ML) methods in combination with explainable ar-tificial intelligence (XAI) tools have proven useful for providing an objective, data-based orien-tation. However, only a few works have considered posture parameters, leaving the potential of more human-friendly XAI interpretations still untouched. Therefore, the present work proposes an objective, data-driven ML system for medical decision support that enables especially human-friendly interpretations using counterfactual explanations (CFs). Posture data for 1151 subjects were recorded by means of stereophotogrammetry. An expert-based classification of the subjects regarding the presence of hyperlordosis or hyperkyphosis was initially performed. Using a Gaussian progress classifier, the models were trained and interpreted using CFs. Label errors were flagged and re-evaluated using confident learning. Very good classification performances for both hyperlordosis and hyperkyphosis were found, whereby the re-evaluation and correction of the test labels led to a significant improvement (MPRAUC = 0.97). A statistical evaluation showed that the CFs seemed to be plausible in general. In the context of personalized medicine, the present study’s approach could be of importance for reducing diagnostic errors and thereby improving the individual adaptation of therapeutic measures. Likewise, it could be a basis for the development of apps for preventive posture assessment.

Little is known about how differences in water availability within the “super humid” tropics can influence the distribution of understory plant species and the composition of understory plant communities. We investigated variation in the physiological drought tolerances of understory plants and plant communities across a large elevation and precipitation gradient. We established 58 understory plots along a gradient of 400 – 3600 m asl elevation and 1000 – 6000 mm yr-1 rainfall in and around Manu National Park in southeastern Peru. Within the plots, we sampled all understory woody plants and measured three metrics of physiological leaf drought tolerance - turgor loss point (TLP), cuticular conductance (Gmin), and solute leakage (SL) - and assessed how the community-level means of these traits related to mean annual precipitation (MAP) and elevation (in the study gradient temperature decreases linearly and vapor pressure deficit increases monotonically with elevation). We did not find any correlations between the three metrics of leaf drought tolerance, suggesting that they represent independent strategies for coping with low water availability. Despite being widely used metrics of leaf drought tolerance, neither TLP nor Gmin showed any significant relationships with elevation or MAP. In contrast, SL, which has only recently been developed for use in ecological field studies, increased significantly at higher precipitations and at lower elevations (i.e., plants in colder and drier habitats have lower SL, indicating greater drought tolerances). Our results illustrate that differences in water availability may play a strong role in structuring plant communities even in in the wet tropics and highlight the potential for SL assays to be an efficient and effective tool for measuring drought tolerances in the field.

Mental wellness can be related to healthier living, the learning process and working environments for people in the university community. A wide range of mental wellness programmes have been explored to provide students with pleasant and satisfying experiences. The purpose of this study is to explore the effects of integrating Zen meditation(禪)and music listening on the mindfulness and happiness levels of university music therapy students. Qualitative methodology was used, and data were collected through surveys and semi-structured interviews. To investigate various aspects of data regarding the role of meditation and music (MM) programme for mindfulness and happiness, this study used thematic analysis within a qualitative research design. The results of this study indicate that the 8-week MM programme is effective in enhancing mindfulness and happiness and has positive responses to daily life stress (e.g., exam anxiety, financial difficulties, and emotional distress during the COVID-19 pandemic). The role of meditation and music in promoting mental health and well-being has long been discussed and the combination of the two has been recognised as a beneficial intervention. This paper could contribute to the support of mental health resources and coping strategies in higher education, as well as expand the potential range of integrating practices involving music and meditation.

Cholangiocellular carcinoma (CCA) is the second most common primary liver cancer, with increasing incidence worldwide and inadequate therapeutic options. Intra- and extrahepatic bile ducts have distinctly different embryonic origins and developmental behavior, and accordingly intra- and extrahepatic CCAs (ICC vs. ECC) are molecularly different. A promising strategy in oncotherapy is targeted therapy, targeting proteins that regulate cell survival and proliferation; such as the MAPK/ERK and PI3K/AKT/mTOR signaling pathways. Inhibitors of these pathways have been tested previously in CCA cell lines. However, these cell lines could not be clearly assigned to ICC or ECC, and results indicated apoptosis induction by targeted therapeutics. We tested targeted therapeutics (selumetinib, MK2206) in three defined ICC cell lines (HuH28, RBE, SSP25). We observed cooperative effects of dual inhibition of the two pathways, in accordance with inhibition of phospho-AKT and phospho-ERK1/2 expression. Proliferation was blocked more effectively with dual inhibition than with each single inhibition, but cell numbers did not drop below baseline. Accordingly, we observed G1-phase arrest, but not apoptosis (cleaved caspase-3, AIFM1 regulation, subG1-phase) or necroptosis (phospho-MLKL). We conclude that dual inhibition of MAPK/ERK and PI3K/AKT/mTOR pathways is highly effective to block proliferation of ICC cell lines, but therapy must certainly be supplemented with standard therapies.

Lifestyle is the primary prevention of diabetes, especially type-2 diabetes (T2D). Nutritional intake of olive oil (OO), the key Mediterranean diet component has been associated with the prevention and management of many chronic diseases including T2D. Several OO bioactive compounds such as monounsaturated fatty acids, and key polyphenols including hydroxytyrosol and oleuropein, have been associated with preventing inflammation and cytokine-induced oxidative damage, glucose lowering, reducing carbohydrate absorption and increasing insulin sensitivity and related gene expression. However, research into the interaction of OO nutraceuticals with lifestyle components, especially physical activity is lacking. Promising postprandial effects have been reported when OO or other similar monounsaturated fatty acids was the main dietary fat compared with other diets. Animal studies have shown a potential anabolic effect of oleuropein. Such effects could be further potentiated via exercise, especially strength training, which is an essential exercise prescription for individuals with T2D. There is also an evidence from in vitro, animal and limited human studies for a dual preventative role of OO polyphenols in diabetes and cancer, especially that they share similar risk factors. Putative anti-oxidative and anti-inflammatory mechanisms and associated gene expressions resulting from OO phenolics, have produced paradoxical results making suggested inferences from dual prevention T2D and cancer outcomes difficult. Well-designed human interventions and clinical trials are needed to decipher such a potential dual anti-cancer and anti-diabetic effects of OO nutraceuticals. Exercise combined with OO consumption, individually or as part of a healthy diet is likely to induce reciprocal action for T2D prevention outcomes.

The cause of sarcoidosis is unknown, and vitamin D is contraindicated to treat the condition. We therefore ask what causes sarcoidosis and why vitamin D can be dangerous for those so afflicted. We propose a contrary hypothesis: sarcoidosis is a physiological process of defense against cancer that requires the substrate vitamin D. We tested this hypothesis, finding many case reports involving sarcoidosis and cancer—further cases of cancer mimicry by sarcoidosis. Several reports describe spontaneous healing of cancer in the presence of sarcoidosis. In the context of the granulomas of sarcoidosis, monocytes are the site of vitamin D release. Furthermore, active vitamin D can control cancer cells by using the vitamin D receptors of the nucleus. That granulomas consistently do not caseate is explained as a confrontation with human molecules and the cancer cells’ complete absorption. The striking fact that granulomas of sarcoidosis mostly lack cancerous cells is interpreted as a result of a well-functioning sarcoidosis process. We view the typical sarcoidosis monocytic synthesis of active vitamin D as a successful defense against cancer: a theory we call the “endogenous program organizing cancer apoptosis” (EPOCA).

Studies of discrete pride in the workplace are both few and on the rise. We examined what has, to date, been yet unstudied: the impact that a leader’s expressions of authentic and hubristic pride can have on the followers at that moment, and on their feelings about their task, leader, and group. Students working in groups building Lego structures rated their perceived leader regarding expressions of pride, both authentic and hubristic. Students who perceived the leader as expressing more authentic pride rated the task, group (satisfaction and cohesion), and leader more positively; while the reverse was generally true for perceptions of expressions of hubristic pride. We found these effects both at the individual level, and at the group level. We also predicted and found moderation for the type of task worked on, creative or detailed. Implications abound for leader emotional labor and emotion management.

Machines for direct digital inkjet printing on cylindrical containers are a new technology out on the market. Their commercialization in the industrial sector has been affected by their high precision. This leads to the use of mechanisms with narrow manufacturing tolerances and to the search for topologies that have the least accumulated error without affecting quality. Machines with topologies to work on flat substrates have printing and productivity problems working on cylindrical substrates. This research paper presents the qualitative design of a direct digital inkjet printer working over cylindrical substrates comparing five mechanical topologies; three topologies with radial distribution and two topologies with parallel distribution. The aim of these topologies is to find the precision, quality and efficiency of the printer taking into account the restrictions present in its construction. Each topology has separate constitutive mechanisms, it is analyzed the tolerance ranges between the print head and the substrate whose cumulative error maximizes the inkjet print resolution to determine precision. From five Topologies, number 1, 2 and 5 meet the requirements. the topology 2 meets the requirements but it is not able to be developed due to current technological limitations.

Knowledge about one’s innate health is central to a variety of positive mental health markers. However, men living in prison rarely receive education about how to access these internal resources. As such, this study seeks to replicate and extend emerging data on an innate health intervention. Volunteers from HMP Nottingham, England (n=126) participated in normal prison programming and the intervention group (n=65) received an additional 3-day intensive. The primary question: Does innate health function as a mediator in the same way self-control does within an incarcerated population? We conducted a mediation analysis, tested social desirability bias, and examined the impact of the intervention on crucial variables. This study found higher levels of innate health, self-control, wellbeing, and prosocial behavior and lower levels of aggression in the intervention group as compared to the control group. Importantly, innate health did play a mediating role equivalent to and/or partnering with self-control.

Background: The frequency of visits to restaurants has been suggested to contribute to the pandemic of obesity. However, few studies have examined how individual use of these restaurants is related to BMI using new technology of reminding to avoid memory error. Aim: To investigate the association between the usage of different types of food outlets and BMI among adults in Scotland. Method: The study was cross-sectional. Participants (n = 681) completed an online survey for seven consecutive days where all food purchased at food outlets was reported each day. We explored the relationship between BMI and usage of these restaurants using auto-reminder text system. Results: Body Mass Index (BMI) of both males and females was not related to frequency of use of Full-Service Restaurants (FSRs), Fast Food Restaurants (FFRs), delivery or takeaways, when assessed individually, or combined (TFO= Total Food Outlet). Conclusion: These data do not support the widespread belief that consumption of food out of the home at fast-food and full-service restaurants, combined with that derived from deliveries and takeaways, is a major driver of obesity in UK.

Corneal diseases are the third leading cause of blindness worldwide. There are numerous causes of corneal blindness, and the common treatment for this condition often involves corneal tissue transplantation, such as Descemet's Membrane Endothelial Keratoplasty (DMEK). DMEK has been established as the preferred surgical technique for the treatment of corneal endothelial disorders. The success of DMEK depends largely on the quality of the donor endothelial cells and the trans-plantation procedure. However, the scarcity of suitable donor tissue and the sensitivity of endo-thelial cells pose a major challenge. In recent years, tissue engineering has attracted attention as potential solutions to these problems. This review offers an outline of the current landscape of DMEK in the context of bioengineering, exploring various methodologies, advancements, and fu-ture prospects.

Education outside the classroom (EOtC) can be beneficial for students. The relationship between biological stress markers and sedentary behavior (SB) plus physical activity (PA) is insufficiently evaluated in school settings. This exploratory study aims to evaluate the association between students’ cortisol, plus circulating cell-free deoxyribonucleic acid (cfDNA) levels, and their SB, light PA (LPA) and moderate-to-vigorous PA (MVPA) during outdoor and indoor classes in different seasons. We assessed data from an education outside the classroom (EOtC) program (n = 48; intervention group [IG], n = 37; control group [CG], n = 11). We sampled data on 3 school-days in three seasons (fall, spring, and summer) in normal teaching indoors (CG) and outdoor lessons (IG) in the forest. SB and PA were evaluated by accelerometry, and cortisol and cfDNA levels by saliva samples. The compositional data analysis approach analyzed SB and PA. Fitted Bayesian hierarchical linear models evaluated the association between cortisol and cfDNA, and SB/LPA/MVPA. A steady decline of cortisol in the outdoor setting is associated with relatively high levels of LPA. SB and MVPA tended to exhibit a similar effect in the indoor setting. CfDNA is positively associated with a relatively high amount of SB in the IG, the same association is likely for LPA and MVPA in both groups. LPA seems to support a healthy cortisol decrease in children during outdoor lessons. The relevance of SB/PA as a composition in relation to students stress response in school should be emphasized. This study facilitates the formulation of straightforward and directed hypotheses for further research.

We bring a strength-based and socially-oriented lens to behaviors observed in profound autism. Social deficits are a defining characteristic of autism. Yet humans’ biological drive for social connection is sufficiently strong that is should be observable, in some form at least, in individuals with autism. We describe a case that validates this view. Mahad is a 20-year-old Pakistani-American male, with intellectual disability, and minimal verbal abilities. Mahad has an intense interest in food and the steps involved in food preparation. He employs and capitalizes on his family’s meal routines to ensure continual social attention from his mother. When not immersed in food, Mahad uses his limited capacities to pursue the additional biological needs of exploring his environment, seeking information, and developing his cognitive abilities.

Appropriate diagnosis, treatment and care contributes to better service engagement, improvements to wellbeing, cost savings, reductions in morbidity and mortality for people with Alcohol Related Brain Damage. In the North-East of England large amounts of alcohol are consumed, reflected in the number of alcohol-related deaths in the region. However, the pathway for people with Alcohol Related Brain Damage to receipt of diagnosis, treatment and care is unknown and could be unwittingly influenced by stigma. Qualitative in-depth semi-structured interviews were completed with 25 health and social care professionals from organisations involved with people with Alcohol Related Brain Damage recruited via snowball-sampling. Interviews were recorded, transcribed verbatim, coded, and analysed. People with Alcohol Related Brain Damage were stigmatised both by society and professionals which inhibited entry into services therefore Alcohol Related Brain Damage remained underdiagnosed and misdiagnosed. There was no dedicated service but silos with revolving doors and underfunded generic care with long waiting lists typically excluding those with alcohol or neurological problems. Professionals need to be challenged on the assumption that Alcohol Related Brain Damage is self-inflicted via training aimed at challenging unconscious bias. Reducing stigmatising processes associated with Alcohol Related Brain Damage could counteract professionals’ reluctance to provide care.

The rapid urbanization that takes place in developing regions such as Sub-Saharan Africa is associated with a large range of environmental and social issues. In this context, remote sensing is essential to provide accurate and up-to-date spatial information to support risk assessment and decision making. However, mapping urban areas remains a challenge because of their heterogeneity, especially in developing regions where the highest rates of misclassification are observed. Nevertheless, urban areas located in arid climates --- which are among the most vulnerables to anthropogenic impacts, suffer from the spectral confusion occurring between built-up and bare soil areas when using optical imagery. Today, the increasing availability of satellite imagery from multiple sensors allow to tackle the aforementioned issues by combining optical data with Synthetic Aperture Radar (SAR). In this paper, we assess the complementarity of the Landsat 8 and Sentinel-1 sensors to map built-up areas in twelve Sub-Saharan African urban areas, using a pixel-level supervised classification based on the Random Forest classifier. We make use of textural information extracted from SAR backscattering data in order to reduce the speckle noise and to introduce contextual information at the pixel level. Results suggest that combining both optical and SAR features consistently improves classification performances, mainly by enhancing the differentiation between built-up and bare lands. However, the fusion was less beneficial in mountainous case studies, suggesting that including features derived from a Digital Elevation Model (DEM) could improve the reliability of the proposed approach. As suggested by previous studies, combining features computed from both VV and VH polarizations consistently led to better classification performances. On the contrary, introducing textures computed from different spatial scales did not improve the classification performances.

The blood-brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important to maintain the BBB integrity, can be functionally modified by GBM cells by inducing proliferation and cell motility via the TGF-β-mediated induction of central epithelial to mesenchymal transition (EMT) factors., We demonstrate that pericytes strengthen the integrity of the BBB in primary endothelial cell/pericyte co-cultures as in vitro BBB model, using TEER measurement of the barrier integrity. In contrast, this effect was abrogated by TGF-β or conditioned medium from TGF-β secreting GBM cells, finally leading to the disruption of a so far intact and tight BBB. TGF-β dramatically changed the metabolic behavior of pericytes, such as shutting down the TCA cycle, driving energy generation from oxidative phosphorylation towards glycolysis, and by shifting the cells towards the activation of pathways that are necessary to produce molecules used for proliferation and cell division. Furthermore, combined metabolomics and RNASeq analyses indicated that the observed functional changes of TGF-β-treated pericytes are closely connected with their behavior.

Introduction Blunt carotid injuries (BCI) in pediatric trauma are quite rare. Due to the low number of cases, only a few reports and studies have been conducted on this topic. This review will discuss how frequent BCI/ BCVI on pediatric patients after blunt trauma is, what routine diagnostics look like, if a CT/ CTA scan on pediatric patients after blunt trauma is always necessary and if there are any negative health effects? Methods This literature review includes reviews, systematic reviews, case reports and original studies in english language between 1999 and 2020 that have dealt with pediatric blunt trauma and the diagnostics of BCI and BCVI. Furthermore, publications on the risk of radiation exposure on children were included in the study. For literature research, Medline (PubMed) and the Cochrane library were used. Results Pediatric BCI/ BCVI, shows an overall incidence between 0.03 – 0.5% of confirmed BCI/ BCVI cases due to pediatric blunt trauma. 1.1 – 3.5% of pediatric blunt trauma patients underwent CTA to detect BCI. Only 0.17 – 1.2% of all CTA scans shows a positive diagnosis for BCI. In children, the median volume CT dose index on a non-contrast head CT is 33 milligray, a computed tomography angiography needs at least 138 mGy. A cumulative doses of about 50 mGy almost triples the risk of leukemia, and doses of about 60 mGy triples the risk of brain cancer. Discussion Knowing that a BCI could have extensive neurologic consequences for children, it is necessary to evaluate routine pediatric diagnostics after blunt trauma. Computed tomography scans (CT) and computed tomography angiography (CTA) are mostly used in routine BCI diagnostics. However, since radiation exposure in children should be as low as reasonably achievable, it should be asked if other diagnostic methods could be used to identify risk groups. Trauma guidelines and clinical scores like the McGovern score are reflect established BCI screening options, as well as using duplex ultrasound.

Wearable technology will become available and allow prolonged electroencephalography (EEG) monitoring in the home environment of patients with epilepsy. Neurologists analyse the EEG visually and annotate all seizures, which patients often under report. Visual analysis of a 24 hour EEG recording typically takes one to two hours. Reliable automated seizure detection algorithms will be crucial to reduce this analysis. We study a dataset of behind-the-ear EEG measurements. Our first aim was to develop a methodology to reduce the EEG dataset by classifying part of the data automatically, while retaining 100% detection sensitivity (DS). Prediction confidences are determined by temperature scaling of the classification model outputs and trust scores. A DS of approximately 90% (99%) can be achieved when automatically classifying around 90% (60%) of the data. Perfect DS can be achieved when automatically classifying 50% of the data. Our second contribution demonstrates that a common modelling strategy, where predictions from several short EEG segments are used to obtain a final prediction, can be improved by filtering out untrustworthy segments with low trust scores. The false detection rate shows a relative decrease between 21% and 43%, and the DS shows a small increase or decrease.

In recent years, Web APIs have become a de facto standard for exchanging machine-readable data on the Web. Despite this success though, they often fail in making resource descriptions interoperable due to the fact that they rely on proprietary vocabularies that lack formal semantics. The Linked Data principles similarly seek the massive publication of data on the Web, yet with the specific goal of ensuring semantic interoperability. Given their complementary goals, it is commonly admitted that cross-fertilization could stem from the automatic combination of Linked Data and Web APIs. Towards this goal, in this paper we leverage the micro-service architectural principles to define a SPARQL Micro-Service architecture, aimed at querying Web APIs using SPARQL. A SPARQL micro-service is a lightweight SPARQL endpoint that provides access to a small, resource-centric, virtual graph. In this context, we argue that full SPARQL Query expressiveness can be supported efficiently without jeopardizing servers availability. Furthermore, we demonstrate how this architecture can be used to dynamically assign dereferenceable URIs to Web API resources that do not have URIs beforehand, thus literally ``bringing'' Web APIs into the Web of Data. We believe that the emergence of an ecosystem of SPARQL micro-services published by independent providers would enable Linked Data-based applications to easily glean pieces of data from a wealth of distributed, scalable and reliable services. We describe a working prototype implementation and we finally illustrate the use of SPARQL micro-services in the context of two real-life use cases related to the biodiversity domain, developed in collaboration with the French National Museum of Natural History.

Phosphorus (P) is a vital macronutrient crucial for crop productivity. Plants absorb P salts, mainly orthophosphate, from soil, yet the primary P source resides in organic materials. Soil phosphomonoesterases (APases) play a vital role in releasing P from organics via hydrolysis. Acid and alkaline phosphatases are crucial for alleviating P deficiency in plants. In this review focused on agricultural soils, we studied the relationship of biophysicochemical, agricultural management, and climate factors on APases also its connection with crop growth and yields. Our findings indicate a strong linkage between both APases and soil pH, positively influenced by clay content, organic matter, microbial biomass carbon, and nitrogen. Adopting healthy soil practices like balanced organic fertilizer usage, optimal soil water levels, reduced tillage, crop rotation, and using beneficial plant microbes help boost APase activity. However, the connection between APases and crop productivity remains uncertain due to insufficient research in this area. Our review emphasizes the vital need to evaluate the relationship between APases and meso-macrofauna, alongside essential plant nutrients such as potassium, nutrient ratios, and the synergistic effects of various factors. Understanding the rapid, efficient assimilation of P through APases in the plant-soil and/or plant-microbiota ecosystem it can be crucial for crop productivity and yields.

Single-particle cryo-electron microscopy (cryo-EM SPA) has recently emerged as an exceptionally well-suited technique for determining the structure of membrane proteins (MPs). Indeed, in the last years, it was observed a huge increase in the number of MPs solved by cryo-EM SPA at a resolution better than 3.0 Å in the Protein Data Bank (PDB). However, sample preparation remains a significant challenge in the field. Here, we evaluated in the MPs solved by cryo-EM SPA deposited in the PDB in the last two years at a resolution below 3.0 Å the most critical parameters for sample preparation: i) the surfactant used for protein extraction from the membrane, ii) the surfactant, amphiphiles, nanodiscs or other molecules present in the vitrification step, iii) the vitrification method employed, and iv) the type of grids used. The aim is not to provide a definitive answer on the optimal sample conditions for cryo-EM SPA of MPs, but rather assess the current trends in the MP structural biology community towards obtaining high-resolution cryo-EM structures.

In a safety-critical system typically not all provided services have the same criticality, which we call mixed-criticality systems. Criticality arithmetic, also called SIL arithmetic, is an approach to lower the development effort of a service by providing redundancy with tasks that are developed for a lower criticality level. In this paper we present ATMP-CA, which is a derivation of the multi-core scheduler ATMP. ATMP-CA is able to take into account the knowledge about the use of criticality arithmetic. ATMP-CA has a modified core allocation and procedure for utility optimisation, considering the context of the replicated tasks. We conducted experiments that show that ATMP-CA is able to provide the services using criticality arithmetic, while the reference schedulers were not.

Companion animals play a central role in many families and are especially valued by those who are socially isolated. Crisis situations such as acute hospitalizations, homelessness and natural disasters can make it difficult to preserve the human-animal bond and can result in animals being surrendered or euthanized. Social support programs like the RSPCA NSW Emergency Boarding and Homelessness program support people experiencing crisis situations with emergency pet boarding, access veterinary treatment and individualized case management. This study aimed to estimate the social return on investment (SROI) for this program using standard SROI methodology. In-depth interviews were conducted with 13 program stakeholders and questionnaire responses were received from 29 program clients. Outcomes were quantified for four stakeholder groups: program clients, client’s animals, RSPCA Inspectors, animal pounds and shelters. Clients and their animals experienced the bulk of the benefit from the program, estimated to have a combined value of over $5 million AUD for the 2020-21 financial year. The estimated social return on investment was $8.21 for each $1 invested. The study demonstrates that keeping people together with their companion animals, or ensuring they are reunited as soon as possible, can reduce stressors, and improve outcomes for people and animals.

Borrelia miyamotoi is an emerging tick-borne pathogen in the Northern hemisphere and is the causative agent of Borrelia miyamotoi disease (BMD). B. miyamotoi is vectored by the same hard-bodied ticks as Lyme disease Borrelia, yet phylogenetically groups with relapsing fever Borrelia, and thus has been uniquely labeled a hard tick-borne relapsing fever Borrelia. Burgeoning research has uncovered new aspects of B. miyamotoi in human patients, nature, and the lab. Of particular interest are novel findings on disease pathology, prevalence, diagnostic methods, ecological maintenance, transmission, and genetic characteristics. Herein we review recent literature on B. miyamotoi, discuss how findings adapt to current Borrelia doctrines, and briefly consider what remains unknown about B. miyamotoi.

Calcium carbonate cements have been synthesized by mixing amorphous calcium carbonate and vaterite powders with water to form a cement paste and study how mechanical strength is created during the setting reaction. In-situ XRD was used to monitor the transformation of ACC and vaterite phases into calcite and a rotational rheometer was used to monitor the strength evolution. There are two characteristic time scales of the strengthening of the cement paste. The short timescale of the order 1 hour is controlled by smoothening of the vaterite grains, allowing closer and therefore adhesive contacts between the grains. The long timescale of the order 10-50 hours is controlled by the phase transformation of vaterite into calcite. This transformation is, unlike in previous studies using stirred reactors, found to be mainly controlled by diffusion in the liquid phase. The evolution of shear strength with solid volume fraction is best explained by a fractal model of the paste structure.

Ustilago maydis, member of the Ustilaginaceae family, is a promising host for the production of several metabolites including itaconic acid. This dicarboxylate has great potential as a bio-based building block in the polymer industry, and is of special interest for pharmaceutical applications. Several itaconate overproducing Ustilago strains have been generated by metabolic and morphology engineering. This yielded stabilized unicellular morphology through fuz7 deletion, reduction of by-product formation through deletion of genes responsible for itaconate oxidation and (glyco)lipid production, and the overexpression of the regulator of the itaconate cluster ria1 and the mitochondrial tricarboxylate transporter encoded by mttA from Aspergillus terreus. In this study, itaconate production was further optimized by consolidating these different optimizations into one strain. The combined modifications resulted in itaconic acid production at theoretical maximal yield, which was achieved under biotechnologically relevant fed-batch fermentations with continuous feed.

Efficiently targeted cancer therapy without causing detrimental side effects is necessary for alleviating patient care and improving survival rates. This paper presents observations of morphological changes in H1299 human lung cancer cells following W-band MMW irradiation (75 – 105 GHz) at a non-thermal power density of 0.2 mW/cm², investigated over 14 days of subsequent physiological incubation following exposure. Microscopic analyses of physical parameters measured indicate MMW irradiation induces significant morphological changes characteristic of apoptosis and senescence. The Immediate short-term responses translate into long-term effects, retained over the duration of the experiment(s); reminiscent of the phenomenon of Accelerated Cellular Senescence (ACS) achieving terminal tumorigenic cell growth. Further, results were observed to be treatment-specific in energy (dose) dependent manner and were achieved without the use of chemotherapeutic agents, ionizing radiation or thermal ablation employed in conventional methods; thereby overcoming associated side effects. Adaptation of the experimental parameters of this study for clinical oncology concomitant with current developmental trends of non-invasive medical endoscopy alleviates MMW therapy as an effective treatment procedure for human non-small cell lung cancer (NSCLC).

Inteins, often referred to as protein introns, are highly mobile genetic elements that invade conserved genes throughout the tree of life. Inteins have been found to invade a wide variety of key genes within actinophages. While in the process of conducting a survey of these inteins in actinophages we discovered that one protein family of methylases contained a putative intein, and two other unique insertion elements. These methylases are known to occur commonly in phages as orphan methylases (possibly as a form of resistance to restriction-modification systems). We found that the methylase family is not conserved within phage clusters and has a disparate distribution across divergent phage groups. We determined that two of the three insertion elements have a patchy distribution within the methylase protein family. We also found that the third insertion element is likely a second homing endonuclease, and that all three elements (the intein, the homing endonuclease, and what we refer to as the ShiLan domain) all have different insertion sites that are conserved in the methylase gene family. Furthermore, we find strong evidence that both the intein and ShiLan domain are partaking in long distance horizontal gene transfer events between divergent methylases in disparate phage hosts within the already dispersed methylase distribution. The reticulate evolutionary history of methylases and their insertion elements reveals high rates of gene transfer and within-gene recombination in actinophages.

Temporomandibular disorders (TMD) affect a high percentage of children and adults worldwide. Surgery may be indicated in severe or recalcitrant case. Several recent advancements in the TMD and temporomanidbular joint (TMJ) surgery have elevated understanding and ability to treat affected patients. We discuss recent advances in TMD epidemiology, juvenile idiopathic arthritis (JIA) of the TMJ, and surgical techniques and technologies. Technical advancements have been identified in TMJ arthroscopy, treatment of TMJ subluxation and dislocation, and extended prosthetic total TMJ reconstruction (eTMJR). Overall, this review provides valuable insights into significant recent advancements of TMJ disorders and their surgical management.

Pediatric obstructive sleep apnea (OSA) has significant negative effects on health and behavior in childhood including depression, failure to thrive, neurocognitive impairment, and behavioral issues. It is strongly associated with an increased risk for chronic adult disease such as obesity and diabetes, accelerated atherosclerosis, and endothelial dysfunction. Accumulating evidence suggests that adult-onset non-communicable diseases may originate from early life through a process by which an insult applied at a critical developmental window causes long-term effects on the structure or function of an organism. Recently, much attention has been paid to the role of epigenetic mechanisms in the pathogenesis of adult disease susceptibility. Epigenetic mechanisms that influence adaptive variability include histone modifications, non-coding RNAs, and DNA methylation. This review will highlight what is currently known about the phenotypic associations of epigenetic modifications in pediatric OSA and will emphasize the importance of epigenetic changes as both modulators of chronic disease and potential therapeutic targets.

Folk nomenclature is habitually established for species that have attained high utilitarian and cultural significance by custodians of such plants worldwide. Such folk names assigned to species often carry etymological values such as therapeutic effects, morphological features, mythical connotations, and their allegorical values. This research sought to unveil the etymology in folk nomenclatures of Sphenostysis stenocarpa (Hosch ex A. Rich) Harms (African Yam Bean). Three hundred and fifty respondents were randomly selected from 13 local communities in Ebonyi State in South-eastern, Nigeria. Data were collected through oral interviews with semi-structural questionnaires, along with focused group discussions. Analysis of data was carried out using simple statistical methods involving frequencies and percentages. The results recorded ten folk nomenclatures assigned to this species in seven dialects affiliated to cultural values within these communities. Etymologically, the results also revealed that out of the ten folk names of AYB cryptic connotations, five reflected their trust in the gods that answered their prayers, two were attributed to the healing potentials inherent in this crop for medicine, three names were associated with the seeds, while one referred to feminist attachment to the crop, another to its resilience/ adaptability to climatic stress and one as a sustainer of farmers. Considering that folk nomenclature is based mainly on qualitative data and the information outside the scientific domain, they are nonetheless highly valued because they are based on long-term interactions, utilization and observations of the custodians of these natural resources. However, these data are equally vulnerable to erosion if not properly documented and conserved for posterity.

Care coordination (CC) for children with special healthcare needs and medical complexity (CSHCN-CMC) is challenging, and medication management is especially difficult for providers, parents/caregivers, and patients alike. While numerous strategies for CC have been suggested and implemented, barriers to medication optimization remain. The report describes the creation of a pediatric clinical pharmacotherapy practice, related standard operating procedures to assure consistent application of screening tools and care provision through comprehensive medication management (CMM), and establishment of a collaborative practice agreement (CPA) to guide drug therapy delegation, monitoring, and modification. The methodology of a prospective case series is also presented to highlight drug therapy problems and their resolution in CSHCN-CMC. Future opportunities to expand the practice for engagement in population health management as well as prior authorization activities on behalf of physicians will be discussed.

Abstract: Plasma hemopexin (HPX) is the key antioxidant protein of the endogenous clearance pathway that limits the deleterious effects of heme released from hemoglobin and myoglobin. During intra-vascular hemolysis, heme partitioning to protein and lipid increases as the plasma concentration of HPX declines. Therefore, the development of HPX as a replacement therapy during high heme stress could be a relevant intervention for hemolytic disorders. A logical approach to enhance HPX yield involves recombinant production strategies from human cell lines. The present study focuses on a biophysical assessment of heme binding to recombinant human HPX (rhHPX) produced in the Expi293FTM (HEK293) cell system. In this report, we examine rhHPX in comparison with plasma HPX using a systematic analysis of protein structural and functional characteristics related to heme binding. Analysis of rhHPX by UV/Vis absorption spectroscopy, circular dichroism (CD), SEC-HPLC and catalase-like activity demonstrated a similarity to HPX fractionated from plasma. In particular, the titration of HPX apo-protein(s) with heme was performed for the first time using a wide range of heme concentrations to model HPX-heme interactions to approximate physiological conditions (from extremely low to more than 2-fold heme excess). The CD titration data showed an induced bisignate CD Soret band pattern typical for plasma and rhHPX versions at low heme-to-protein molar ratios and demonstrated that further titration is dependent on the amount of protein-bound heme to the extent that the arising opposite CD couplet results in a complete inversion of the observed CD pattern. The data generated in this study suggests more than one binding site in both plasma and rhHPX. Further, our study provides a useful analytical platform for detailed characterization of HPX-heme interactions and potentially, novel HPX fusion constructs.

While molecular methods have begun to transform ecology, most algal biodiversity is still studied using the classical approach of identifying microalgae by light microscopy directly in sample material or using cultures. In this study, we compare both approaches (light microscopy and metagenomics as a molecular approach) using freshwater ponds of the Eifel National Park in Germany as a case study. The ponds were found to be rich in desmids by light microscopy. A total of 299 species representing 81 genera were identified by light microscopy. While the molecular method does not currently allow species identification in most cases, we were able to identify 207 different algal genera. 157 genera were detected only by metagenomics, 50 genera with both methods and 31 genera were found by light microscopy, highlighting the need to continue using light microscopy in addition to a molecular approach. The metagenomics method has several advantages over the light microscopy method: 1) deeper assessment of alpha biodiversity 2) better abundance numbers 3) complete coverage of all living matter. The latter is also a significant improvement over metabarcoding, as universal PCR primers are not available.

Androgen deprivation therapy (ADT) for prostate cancer treatment is associated with adverse physiological changes, however exercise can improve outcomes. This systematic review and meta-analysis aimed to determine exercise intervention adherence, and its effects on physiological outcomes in men diagnosed with prostate cancer undergoing ADT. Uniquely, this review incorporates a meta-aggregation of qualitative data, providing perspectives from the men’s experiences. A systematic review and meta-analysis were completed following PRISMA Guidelines. Databases (CINAHL, Cochrane, PubMed) were searched for studies using “prostate cancer”, “exercise intervention”, and “androgen deprivation therapy”. Quantitative randomised controlled trials describing adherence to exercise interventions were selected, with qualitative articles selected based on descriptions of experiences around participation. Subgroup meta-analyses of adherence, exercise mode, and intervention duration were completed for quality of life, aerobic fitness, fatigue, and strength. Articles (n=64) articles were identified, with 29 (n=23 quantitative; n=6 qualitative) articles from 25 studies included. Exercise had no effects (p<0.05) on quality of life and fatigue. Significant effects (all p<0.05) were observed for aerobic fitness, and upper- and lower-body strength. Adherence to exercise-based interventions was 80.38%, with improvements observed in aerobic fitness and strength. Subgroup analysis revealed exercise adherence impacted fatigue and strength, with greater improvements observed in programs >12-weeks.

contaminated sites located in each school district. Previous studies showed that various environmental factors, such as exposure to toxic substances negatively impacts human health depending on their concentration and occurrence. Therefore, the study aims to use Geographical Information System (GIS) technology and secondary data on IEP numbers of each school district, chemical occurrence in contaminated sites, and demographic data to conduct a correlational analysis. The secondary data obtained from school districts and contaminated sites from Iowa Department of Natural Resources Facility Explorer were populated in ArcMap 10.5 (a GIS software) for generating maps and data to conduct statistical analysis. The contaminants were categorized into metals, polyaromatic hydrocarbons (PAH), and solvents with weighing factors as 1, 0.5, and 0.25. A total of 1 Superfund site and 39 CERCLA sites were identified as contaminated sites for this study. The majority of contaminants were heavy metals such as lead, arsenic, mercury, and cadmium. The mean toxic score of all contaminated sites combined was 13.4 (sd 14.4). The correlational analysis between the IEP numbers from each school districts and toxic scores from the contaminated sites was positive indicting that increased toxic score increased the number of students enrolled in the IEP program (F=23.7, p<0.0001). The correlational analysis between toxic score and demographics indicated some interesting results. Children under the age of 10 were living in areas with high toxic score and the showed mild correlation (p<0.00052). Similarly, higher number of black population resided in areas with high toxic score (p=0.0032) than the white population (p<0.0001). The result also indicated that children enrolled in IEP were predominantly among the black population (p<0.0001). The correlational analysis between household income and poverty percentage of people residing near the contaminated area indicated that people had low average household income (p=0.0002) and high poverty percentage (p=0.0203) residing in areas with higher toxic score. Regarding the educational status, less number of people with post graduate degree (p<0.0001) resided in areas with high toxic score and more number of people with no degree (p<0.0001) resided in areas with high toxic score. Finally, the study showed the increasing trend of eligible children enrolling in free and reduced lunch programs with increasing toxic scores (p=0.0012) and IEP levels (p=0.0416). This study emphasize on developing multiple exposure to correlate environmental factors contributing to the negative health outcome on people.

Caring for an ill or disabled relative can present significant challenges that may exceed the per-sonal resources of the caregiver. Young carers (YCs) often take on this role, providing support to family members or friends, which can have far-reaching effects on various aspects of their lives. This study involved 235 adolescents, 106 YCs and 129 non-carers (NCs), who completed ques-tionnaires assessing life satisfaction, social support, family functioning, academic functioning, and caring activities. Group effects measured with MANOVA and MANCOVA (controlling for age effects), showed YCs to have higher amounts of caregiving activities than NC (as expected) but lower satisfaction with life. Hierarchical regressions also found that, for YCs, academic func-tioning, social support and the negative impact of caregiving predicted satisfaction with life; and that the negative impact of caregiving on YCs is explained by their family functioning and the amount of their caregiving activities. For NCs, only academic functioning, social support and family functioning predicted satisfaction with life. In conclusion, caregiving has a negative im-pact on YC’s life satisfaction, but this effect is determined by their social support, academic func-tioning and negative impact of caring, which in turn depends on their familiar functioning and amount of caring activities.

The level of ambiguity in describing glycan structure has significantly increased with the upsurge of large scale glycomics and glycoproteomics experiments. Consequently, an ontology-based model appears as an appropriate solution for navigating this data. However, navigation is not sufficient and the model should also enable advanced search and comparison. A new ontology with a tree logical structure is introduced to represent glycan structures irrespective of the precision of molecular details. The model heavily relies on the GlycoCT encoding of glycan structures. Its implementation in the GlySTreeM knowledge base was validated with GlyConnect data and benchmarked with the Glycowork library. GlySTreeM is shown to be fast, consistent, reliable and more flexible than existing solutions for matching parts of or whole glycan structures. The model is also well suited to painless future expansion. Availability:https://glyconnect.expasy.org/glystreem/wiki

Rural landscapes all over the world are subject to great transformations, first of all the continuous and slow depopulation of land and villages. It is a dramatic phenomenon that causes devastating consequences for environmental systems and for the tangible and intangible heritage of entire territories. The situation becomes more ambiguous when it comes to cultural landscapes, especially those internationally recognized as exceptional (i.e. inscribed on the UNESCO World Heritage List). In this case, the risk is to abandon agricultural production in favor of consumerist tourist economies, which can damage the territorial authenticity. In this paper we question the role of the landscape project in strengthening territorial resilience. In particular, a composite and interdependent action is proposed between landscape design and implementation of a multifunctional agriculture model, oriented towards teaching and tourism. To undertake this investigation, a master's thesis work on Landscape Architecture is examined, as an opportunity for a research-by-design method. The application case is the Italian UNESCO site of Vignale Monferrato, a depopulated rural village, characterized by abandoned land and buildings. The paper concludes by outlining replicability application scenarios for the proposed model.

The rich emission and absorption line spectra of Fe I may be used to extract crucial information on astrophysical plasmas, such as stellar metallicities. There is currently a lack, in quality and quantity, of accurate level-resolved effective electron-impact collision strengths and oscillator strengths for radiative transitions. Here, we discuss the challenges in obtaining a sufficiently good structure for neutral iron and compare our theoretical fine-structure energy levels with observation for several increasingly large models. Radiative data is presented for several transitions for which the atomic data is accurately known.

SMARCA4-deficient non-small cell lung cancer (NSCLC) is a more recently recognized subset of NSCLC. We describe the 18F-fluorodeoxyglucose (FDG) PET/CT findings in a rare case of SMARCA4-deficient NSCLC and response to therapy. A 45-year-old male patient with a history of heavy smoking (10 years) underwent an 18F-fluorodeoxyglucose (FDG) PET/CT dynamic (chest) + static (whole-body) scan for diagnosis and pre-treatment staging. 18F-FDG PET/CT showed an FDG-avid mass in the upper lobe of the left lung (SUVmax of 22.4) and FDG-avid lymph nodes (LN) in the left pulmonary hilar region (SUVmax of 5.7). In addition, there are multiple metastases throughout the body, including distant LNs, adrenal glands, bone, and brain. Pathological findings confirmed SMARCA-4 deficient NSCLC. After 4 cycles of chemotherapy and immune checkpoint inhibitors（ICI）, the patient underwent again an 18F-FDG PET/CT scan (including dynamic scan) for efficacy evaluation. We report cases that deepen the understanding of the 18F-FDG PET/CT presentation of SMARCA4-deficient NSCLC as well as dynamic imaging features and parametric characteristics.

The study evaluated the functional and sensory properties of infant complementary foods formulated from millets, orange-flesh sweet potatoes, carrots, periwinkle and oyster. Experimental/cross-sectional design was used. Millet, orange-flesh sweet potato (OFSP), carrots, periwinkle and oyster were purchased, processed into flour using standard methods. The complementary food was formulated on protein basis for infants 6–12 months. The formulated foods were millet/OFSP flours (70:30), millet/OFSP/carrot/periwinkle (49:29:7:15), and millet/OFSP/carrot/oyster (65:20:5:10). Functional properties were carried out using standard methods. Sixty nursing mothers attending Orogbum Health Centre were systematically sampled for the sensory evaluation. ANOVA was used for the study. The result showed packed density (0.77 g/mL) was significantly higher (p < 0.05) in food formulated from millets/OFSP than in millet/OFSP/carrot/oyster (0.68 g/mL). Loosed density was lowest (0.40 g/mL) in millet/OFSP/carrot/oyster. Carr index from ranged from 42.23 in millet/OFSP/carrot/oyster to 44.41 in millet/OFSP. Wettability was highest (45.03) in millet/OFSP/carrot/periwinkle compared to wettability value (26.53) for millet/OFSP. Solubility ranged from 18.36 to 46.62, with the highest (46.62) in millet/OFSP/carrot/periwinkle. The peak viscosity of the infant complementary food samples ranged from 64.53 rapid visco analyzer units (RVU) to 89.33 RVU. The infant complementary food formulated from millet/OFSP had significantly higher (p < 0.05) acceptability score (6.35).

Meprin α and β are zinc-dependent proteinases implicated in multiple diseases including cancers, fibrosis, and Alzheimer’s. However, until recently, only a few inhibitors of either meprin were reported and no inhibitors are in pre-clinical development. Moreover, inhibitors of other metzincins developed in previous years are not effective in inhibiting meprins suggesting the need for de novo discovery effort. To address the paucity of tractable meprin inhibitors we developed ultra-high throughput assays and conducted parallel screening of >650,000 compounds against each meprin. As a result of this effort, we identified 5 selective meprin α hits belonging to three different chemotypes (triazole-hydroxyacetamides, sulfonamide-hydroxypropanamides, and phenoxy-hydroxyacetamides). These hits demonstrated a nanomolar to micromolar inhibitory activity against meprin α with low cytotoxicity and >30-fold selectivity against meprin β and other related metzincincs. These are the most selective inhibitors of meprin α to date.

Copper-containing materials are attracting attention as self-desinfecting surfaces, suitable for helping healthcare settings in reducing healthcare associated infections. However, the impact of repeated exposure to disinfectants frequently used in biocleaning protocols on their antibacterial activity remains insufficiently characterized. This study aimed at evaluating the antibacterial effi-ciency of copper (positive control), a brass alloy (AB+®) and stainless steel (negative control) after repeated exposure to a quaternary ammonium compound and/or a mix of peracetic acid/hydrogen peroxide routinely used in healthcare settings. A panel of 6 antibiotic-resistant strains (clinical isolates) was selected for this assessment. After a short (5 min) exposure time, the copper and brass materials retained significantly better antibacterial efficiencies than stainless steel, whatever the bacterial strain or disinfectant treatment considered. Moreover, post-treatment with both disinfectant products, copper-containing materials still reached similar levels of antibacterial efficiency as those obtained before treatment. Antibiotic resistance mechanisms such as efflux pump overexpression did not impair the antibacterial efficiency of copper-containing materials, neither did the presence of one or several genes related to copper homeostasis/resistance. In light of those results, surfaces made out of copper and brass remain interesting tools in the fight against dissemination of antibiotic-resistant strains that might cause healthcare associated infections.

A low-resource emotional speech synthesis system for empathetic speech synthesis based on modelling prosody features is presented here. Secondary emotions, identified to be needed for empathetic speech, are modelled and synthesised in this paper. As secondary emotions are subtle in nature, they are difficult to model compared to primary emotions. They are also less explored, and this is one of the few studies that model secondary emotions in speech. Current speech synthesis research uses large databases and deep learning techniques to develop emotion models. There are many secondary emotions, and hence, developing large databases for each of the secondary emotions is expensive. This research presents a proof-of-concept using hand-crafted feature extraction and modelling of these features using a low resource-intensive machine learning approach, thus creating synthetic speech with secondary emotions. Here, a quantitative model-based transformation is used to shape the emotional speech fundamental frequency contour. Speech rate and mean intensity are modelled via rule-based approaches. Using these models, an emotional text-to-speech synthesis system to synthesise five secondary emotions - anxious, apologetic, confident, enthusiastic and worried is developed. A perception test to evaluate the synthesised emotional speech is also conducted.

We investigated 328 SARS-CoV-2 cases in Barwon South West Victoria, Australia, in the 2020 pre-vaccination period, comparing infections with symptoms to those that remained asymptomatic. De-identified self-reported data from three sequential questionnaires on case characteristics and symptom progression were examined. Multivariable logistic regression were used to model associations between demographic profile and symptoms. Asymptomatic cases were more than three times as likely to be from ethnic minority groups [OR 3.2, 95% CI 1.5 – 6.7, p&lt;0.01], and approximately seven times more likely to be seniors (≥ 65 years) [OR 7.3, 95% CI 1.0 – 50.1] after adjusting for sex and occupation. The overrepresentation of ethnic minority groups among asymptomatic infections is suggestive of genetic haplotype variability by ethnic group, conferring greater cross protection from other coronaviruses in the early stages of the COVID-19 pandemic. This research should be repeated post-vaccination to reassess symptom expression according to ethnicity, and better comprehend case ascertainment impacts of cultural biases in testing and infection reporting, and the reliance on symptoms to trigger testing. These findings may in part reflect differences in testing patterns by ethnicity and true differences in disease expression, both important for appropriate transmission prevention strategies, and tailoring testing messaging towards ethnic minority communities.

Saccharomyces cerevisiae are a phenotypically diverse species that adapt to a wide variety of environments by exploiting standing genetic diversity and selecting for advantageous mutations. Glyphosate and copper-based herbicides/ fungicides affect non-target organisms, these incidental exposures can impact microbial populations. In this study, glyphosate resistance was found in the historical collection of yeast which was collected over the last century, but only in yeast isolated after the introduction of glyphosate. The highest glyphosate-resistant yeasts were isolated from agricultural sites. However, herbicide application at these sites was not recorded. In an effort to assess glyphosate resistance and impact on non-target microorganisms, yeast were harvested from 15 areas with known herbicidal histories, including an organic farm, conventional farm, remediated coal mine, suburban locations, state park, and a national forest. Yeast representing 23 genera were isolated from 237 samples of plant, soil, spontaneous fermentation, nut, flower, fruit, feces, and tree material samples. Saccharomyces, Candida, Metschnikowia, Klyveromyces, Hanseniaspora, and Pichia were other genera commonly found across our sampled environments. Managed areas had less species diversity and at the brewery, only Saccharomyces and Pichia were isolated. A conventional farm growing RoundUp Ready™ corn had the lowest phylogenetic diversity and the highest glyphosate resistance. The mine was sprayed with multiple herbicides including a commercial formulation of glyphosate; however, the yeast did not have elevated glyphosate resistance. In contrast to the conventional farm, the mine was exposed to glyphosate only one year prior to sample isolation. Glyphosate resistance is an example of the anthropogenic selection of nontarget organisms.

The purpose of this scoping review was to examine the literature on the use of anti-gravity treadmill and its effects on lower limb motor functions in children and adolescents with locomotor impairments. Four databases (MEDLINE, CINAHL, Embase, Web of Science) were searched for articles from inception to August 2021. Inclusion criteria were: (1) experimental or quasi-experimental studies using the anti-gravity training as the primary intervention; (2) studies conducted in paediatricpediatric participants; (3) articles reporting outcomes related to the lower limb functions; and (4) studies published in French or English. Fifteen articles were included in the review. Studies included children and adolescents aged 4–18 years with locomotor impairments. The intervention duration was ranged from 2 and to 12 weeks, with 2-5 sessions per week. Included studies showed reported that anti-gravity training induces improvements in muscle strength, balance, spatiotemporal gait parameters, and walking endurance in children with locomotor impairments. This review provides relevant information about the modalities, outcomes and limits associated with the anti-gravity training protocol reported in the literature. Overall, the anti-gravity treadmill training could be viewed as a valuable training modality for children with cerebral palsy. However, more precise, and comprehensive description of anti-gravity rehabilitation protocols would be useful.

Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin α-specific inhibition through an HTS effort (see part I, preceding paper). In part II we report the optimization of a potent and selective hydroxamic acid meprin α inhibitor probe which may help define the therapeutic potential for small molecule meprin α inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition.

In recent years, technical processes for the sequestration of CO2 through industrial waste mineral carbonation have been explored and developed. There is a large portfolio of Carbon Capture, Uti-lisation and Storage (CCUS) techniques that have been employed on a laboratory and at pilot scale. These include geological storage, ocean storage and mineralisation by carbonate ores. In view of this, the main purpose of this research was to investigate and explore chemical variables, particularly ammonium salts as lixiviants for calcium mineral extraction from iron making slag. The slag in use was acquired from a Steel Mill in the Vaal Triangle Region in Gauteng, South Af-rica. The experimental test work was conducted using different ammonium lixiviants, namely, NH4NO3, NH4Cl and CH3COONH4 to understand the influence of anion type as well as possible differences in mechanisms of interactions. Lixiviant concentration as well as the reaction time were varied in this research study. The three selected ammonium based lixiviants showed different extents of calcium extraction owing to differences in the anion groups. NH4NO3, NH4Cl and CH3COONH4 were found capable of dissolving 50% to 80% of calcium from the selected slag for different molar concentrations. Anion type and leaching time also had significant influences on the leaching of calcium from the slag. Rapid pH degradation resulted in better calcium extraction ca-pabilities. This work has shown that the selected ammonium salts have a potential as lixiviants for calcium dissolution from iron making blast furnace slags. These lixiviants would therefore be important to consider during calcium mineral carbonation for CO2 sequestration.

The present investigation focuses on the impact of jet nozzle orientation on mixing time in a cylindrical tank. The aim is to identify nozzle positions that improve mixing performance and to elucidate the governing parameters that influence it. A water tank was employed for the experiment. The vertical inclination angle (α) and the horizontal inclination angle (β) of the jet nozzle determined the nozzle positions. Mixing time was determined using an inert tracer and spectrophotometry measurements. The findings show that the mixing time is significantly influenced by the position of the jet nozzle position. The accuracy of existing jet turbulence and the circulation models for the prediction of mixing time was evaluated for the different nozzle positions. Our results indicate that both models provide accurate predictions for the conventional centrally aligned (β = 0°), upward-pointing jet nozzle positions only (α > 0). For the other nozzle positions where β > 0° and at varying α, the data follow the same trends as the jet turbulence and circulation models, however, the proportionality constants vary. Shorter mixing times can be attributed principally to longer jet path lengths and therefore higher fluid entrainment and circulation, as well as higher dissipation rates per jet length squared. However, it is suspected that the 3-dimensional nature of the flow pattern generated in the tank also plays a non-negligible role since mixing is hindered when the nozzle points more towards the tank wall.

There is an increasing clinical need to develop novel biomaterials that combine regenerative and biocidal properties. In this work, we present the preparation of silver /silica based glassy bioactive (ABG) compositions via a facile, fast (20h), and low temperature (80 °C) approach and their characterization. The fabrication process included the synthesis of the bioactive glass (BG) particles followed by the surface modification of the bioactive glass with silver nanoparticles. The microstructural features of ABG samples before and after exposure to simulated body fluid (SBF) as well as their ion release behavior during SBF test were evaluated using infrared spectrometry (FTIR), ultraviolet- visible (UV-Vis) spectroscopy, X-ray diffraction (XRD), electron microscopies (TEM and SEM) and optical emission spectroscopy (OES). The antibacterial properties of the experimental compositions were tested against Escherichia coli (E. coli). The results indicated that the prepared ABG materials possess antibacterial activity against E. coli, which is directly correlated with the glass surface modification.

Obesity in children is associated with vitamin D (VD) deficiency and cardiometabolic abnormalities. To analyze the effects of VD supplementation in adolescents with obesity enrolled in a weight-loss program. Adolescents with obesity (n=26) and with normal weight (n=23; controls) were matched for age, sex, and puberty stage. The obesity group followed a 3-month weight-loss program that combined a reduced caloric intake with interval training physical activity and during which they received or not VD supplementation (4000 IU/d) (n=13/group; random assignation). The anthropometric parameters (BMI z-score, fat mass); serum levels of 25(OH)D, calcium and parathyroid hormone (PTH), cardiometabolic factors (triglycerides, HDL, and LDL cholesterol), fasting glucose and insulin, and homeostasis model assessment of insulin resistance index; diastolic, systolic and mean blood pressure, and inflammatory status (C-reactive protein, CRP) were measured at baseline and at the end of the 3-month program. At baseline, 25(OH)D concentration was lower and VD insufficiency (25(OH)D levels <50 nmol/L) rate was higher (73% vs 22%) in the obesity than in the normal-weight group. All cardiometabolic factors were altered in the obesity compared with the normal-weight group. After the 3-month weight-loss program, 25(OH)D levels was >50 nmol in all adolescents with obesity, but only in 46% of normal-weight adolescents. Moreover, the weight-loss program improved the cardiometabolic factors, inflammatory status (CRP) and physical performance, but VD supplementation did not have any additional effect. Analysis only of the adolescents with obesity and VD deficiency (25(OH)D <50 nmol/L) at baseline showed a significant correlation between the change in PTH and CRP (p=0.02) in the supplemented obesity group, while the increase in 25(OH)D only tended to be correlated with CRP decrease. Vitamin D supplementation could reduce VD insufficiency in adolescent with obesity, but does not have any additional effect on cardiometabolic factors when combined with a weight-loss program.

The protozoan parasite Plasmodium falciparum is the causative pathogen of the most severe form of malaria, for which novel strategies for treatment are urgently required. The primary energy supply for intraerythrocytic stages of Plasmodium is the production of ATP via glycolysis. Due to the parasite’s strong dependence on this pathway and significant structural differences of its glycolytic enzymes compared to their human counterpart, glycolysis is considered as a potential drug target. In this study, we provide the first three-dimensional protein structure of P. falciparum hexokinase (PfHK), containing novel information about the mechanisms of PfHK. We identified for the first time a Plasmodium-specific insertion which lines the active site. Moreover, we propose that this insertion plays a role upon ATP binding. Residues of the insertion further seem to affect the tetrameric interface and therefore suggest a special way of communication among the different monomers. In addition, we confirmed that PfHK is targeted and affected by oxidative posttranslational modifications (oxPTMs). Both Sglutathionylation and Snitrosation revealed an inhibitory effect on the enzymatic activity of PfHK.

(1) Background: The mediolateral patella displacement is of interest for diagnostics and clinically relevant research questions. Apart from manual testing, no standardized method is currently available. Proper quantification of patella mobility is necessary to understand pathologies at the patellofemoral joint better; (2) Methods: Patella mobility was assessed in 25 healthy individuals using a Patellostabilometer, a new prototype instrument for quantification of the mediolateral patella displacement. The participants underwent measurements of the mediolateral displacement three times using the Patellostabilometer. A maximal force of 10N was applied for patella movement. Additionally, leg length, circumference of the knee, upper- and lower leg was measured. (3) Results: Lateral patella displacement of 18.27±3.76 mm (range 15.85-20.64mm, interquartile range (IQR) of 4.79) was measured. The medial patella displacement showed 24.47±6.59mm (range 19.29-29.76mm, IQR of 10.47). The test-retest measurement error was 2.32±1.76mm (IQR of 2.38mm), with five outliers. There was greater test-retest variability between the measurements of the medial displacement comparing to the lateral one (4) Conclusions: The test-retest variability reached 7% of the patella displacement. Other parameters provided no significant correlations. Based on the natural patellofemoral mobility a precise and clinically relevant quantification of patella mobility is allowed.

In medico-administrative database, certain prognostic factors cannot be taken into account. The main objective was to estimate the performance of two models based on two databases: Epi-thor clinical and medico-administrative databases. For each of the two databases, we randomly sampled a development dataset with 70% of the data and a validation dataset with 30%. Performance of models was assessed by Brier score, the area under the receiver operating characteristic (AUC ROC) curve and the calibration of the model. For Epithor and medico-administrative databases, the development dataset included 10,516 patients (with resp. 227 (2.16%) and 283(2.7%) deaths) and the validation dataset included 4,507 patients (with resp. 93 (2%) and 119 (2.64%) deaths). 15 predictors were selected in the models (including FEV, Body Mass Index, ASA score and TNM stage for Epithor). The Brier score values were similar in the models of the two databases. For validation data, the AUC ROC curve was 0.73 [0.68-0.78] for Epithor and 0.8 [0.76-0.84] for medico-administrative databases. The slope of the calibration plot was less than 1 for the two databases. This work shows the good performances of a model developed from a medico-administrative database, despite the absence of clinical variables used in practice by surgeons, such as FEV1, ASA score or TNM stage.

Rotavirus (RV) replicates within viroplasms, membrane-less electron-dense globular cytosolic inclusions with liquid-liquid phase properties. In these structures occur the virus transcription, replication, and packaging of the virus genome in newly assembled double-layered particles. The viroplasms are composed of virus proteins (NSP2, NSP5, NSP4, VP1, VP2, VP3, and VP6), single and double-stranded virus RNAs, and host components such as microtubules, perilipin-1 and chaperonins. The formation, coalescence, maintenance, and perinuclear localization of viroplasms rely on their association with the cytoskeleton. A stabilized microtubule network involving microtubules and kinesin Eg5 and dynein molecular motors is associated with NSP5, NSP2, and VP2, facilitating dynamic processes such as viroplasm coalescence and perinuclear localization. Key post-translation modifications, particularly phosphorylation events of RV proteins NSP5 and NSP2, play pivotal roles in orchestrating these interactions. Actin filaments also contribute, triggering the formation of the viroplasms through the association of soluble cytosolic VP4 with actin and the molecular motor myosin. This review explores the evolving understanding of RV replication, emphasizing the host requirements essential for viroplasm formation and highlighting their dynamic interplay within the host cell.

The progressive impairment analysis in gait from neurological diseases patients such as Hereditary Ataxias (HA) has been carried out using gait data collected with movement sensors. This research is focused on finding the minimum amount required of gait features to recognize efficiently and less intrusive way, HA patients based on data collected with iPhone movement sensors placed on the ankles from 14 HA patients and 14 healthy people. A twofold proposal is made , first a local minimum prominent peak criterion to find out the starting point of each stride, to get 10-stride window about which 56 spatial-temporal features are derived; second a search strategy based on Hill Climbing algorithm to reduce the number of gait features and sensors. The main results were the findings that with two gait patterns a 96% of classification accuracy was achieved by using K-Nearest Neighbors (KNN) and Multi-Layer Perceptron (MLP) algorithms, but in addition, MLP only right ankle sensor patterns were required which also allows to reduce the intrusion.

The spectra currently emerging from modern ground- and space-based astronomical instruments are of exceptionally high quality and resolution. To meaningfully analyse these spectra researchers utilise complex modelling codes to replicate the observations. The main inputs to these codes are atomic data such as excitation and photoionisation cross sections as well as radiative transition probabilities, energy levels and line strengths. In this publication the current capabilities of the numerical methods and computer packages used in the generation of these data are discussed. Particular emphasis is given to Fe-peak species and the heavy systems of tungsten and molybdenum. Some of the results presented to highlight certain issues and/or advances have already been published in the literature, while other sections present, for the first time, new recently evaluated atomic data.

Antibiotic resistant Pseudomonas aeruginosa infections are the primary cause of mortality in people with cystic fibrosis (CF). Yet it has only recently become appreciated that resistance mutations can also increase P. aeruginosa virulence, even in the absence of antibiotics. Moreover, the mechanisms by which resistance mutations increase virulence are poorly understood. In this study we tested the hypothesis that mutations affecting efflux pumps can directly increase P. aeruginosa virulence. Using genetics, physiological assays, and model infections, we show that efflux pump mutations can increase virulence. Mutations of the mexEF efflux pump system increased swarming, rhamnolipid production, and lethality in a mouse infection model, while mutations in mexR that increased expression of the mexAB-oprM efflux system increased virulence during an acute murine lung infection without affecting swarming or rhamnolipid gene expression. Finally, we show that an efflux pump inhibitor, which represents a proposed novel treatment approach for P. aeruginosa, increased rhamnolipid gene expression in a dose-dependent manner. This finding is important because rhamnolipids are key virulence factors involved in dissemination through epithelial barriers and cause neutrophil necrosis. Together, these data show how current and proposed future anti-Pseudomonal treatments may unintentionally make infections worse by increasing virulence. Therefore, treatments that target efflux should be pursued with caution.

Greek yogurt (GY), a high-protein-low-fat dairy product, particularly prized for its sensory and nutritional benefits, revolutionized the North American yogurt market in less than a decade, bringing with it new sustainability challenges. The standard production of GY generates large volumes of acid whey, a co-product that is a potential source of environmental pollution if not recovered. This study aims to assess the environmental performance of different technologies and identify the main factors for improving GY production. A complete life cycle assessment (LCA) was performed to compare the standard technology (centrifugation) with two new technologies (fortification and ultrafiltration) to reduce acid whey volumes. Three milk protein concentrate alternatives were also assessed. Results show that the technology choice is not a clear discriminant factor. However, minimizing losses and wastage (accounting for 23 to 25% of the environmental impacts for all indicators) beyond the processing plant and selecting milk ingredients (accounting for 63 to 67% of the impacts) with low environmental impacts are key factors in improving the environmental performance of GY systems. From a methodological perspective, the results also highlight a shortcoming in the current International Dairy Federation LCA guidelines (2015) for treating the multifunctionality of GY systems.

The Mediterranean diet (MedDiet) is recognised to reduce risk of coronary heart disease (CHD), in part, via its anti-inflammatory properties. Diet efficacy via this mechanism is however unclear in patients with diagnosed CHD. This study aimed to determine the effect of MedDiet versus low-fat diet intervention on inflammatory biomarkers and adiposity in a pilot cohort of Australian patients post coronary event. Participants (62±9 years, 83% male) were randomised to the MedDiet (n=34) or low-fat diet (n=31). At 0-, 3- and 6-months, dietary counselling, anthropometry, body composition (Dual-energy X-ray Absorptiometry) and venepuncture was conducted. Participants adhered well to the MedDiet intervention, however, there were no significant changes in body composition or inflammatory biomarkers hs-C-reactive protein or hs-interleukin-6 in the MedDiet compared to the low-fat diet group after 6-months. Adiponectin, an anti-inflammatory adipokine, tended to increase in response to the MedDiet (+1.1±4.2ng/mL, p=0.11) and decrease in response to the low-fat diet (-0.9±3.3ng/mL, p=0.20). In the pooled cohort, participants with greatest improvement in MedDiet adherence score had significantly lower waist circumference and subcutaneous fat levels at 6-months. A clinically significant effect of the MedDiet on inflammation and adiposity in CHD patients may require a larger sample, adjunct exercise intervention and/or caloric restriction.

The use of recombinant bovine somatotropin (rbST) leads to an increase, in variable amounts, of milk production in buffalo, but there is a lack of information on the influence of rbST on their metabolism. This study looked at the effects of a single 500 mg dose of rbST on lipid profile, liver and kidney function and physical, chemical and cellular constitution of milk in 14 buffalo over 14 days, from the 100th day of lactation, and compared them with 14 animals in a control group. From the 1st day after rbST, there was a rise in beta hydroxybutyrate (β-HBO), possibly due to the higher dry matter intake or by biotransformation of NEFA into β-HBO. Treatment did not influence blood glucose, non-esterified fatty acids (NEFA), triglycerides, cholesterol, total protein, albumin, AST, GGT, bilirubin, urea or creatinine. In 71.3% of the buffalo there was a gradual increase in milk production with maximal response in the first week that was then followed by a gradual decrease, whilst in 21.4%, the increase in production occurred between 7 and 10 days, and only 7.1% of animals did not respond. On the 3rd, 5th, 7th and 10th days after treatment, an increase was found in milk production between the two groups equal to 1.04, 1.52, 1.42 and 1.06 liters, respectively. In relative terms this means an increase in milk production, respectively, of 15.1%; 21.0%; 19.8 % and 15.1 %. The constitution of the milk showed no difference in the amounts of fat, lactose, total solids or somatic cell count; however, on the 3rd day after rbST, there was a decrease in protein; notably, from the 5th day, protein values show no statistical difference. It can be concluded that the application of rbST in buffalo from the 100th day of lactation is metabolically safe, since the treatment neither caused imbalances in fat metabolism nor overloaded the liver or renal function, and the changes in milk composition were transient and limited to a decrease in milk protein.

Background and aim: To explore the discriminant accuracy of Cytokeratin 18 (CK18, including M65 and M30 forms) for an elevated fatty liver index (FLI) as a validated proxy of Non-Alcoholic Fatty Liver Disease (NAFLD), and cardiovascular disease (CVD) risk in the general population. Methods: Both serum CK18 forms were measured using a commercial immunoassay in randomly selected samples from 312 participants of the PREVEND general population cohort. FLI ≥60 was used to indicate NAFLD. Framingham Risk Score (FRS) and the SCORE2 were used to estimate the 10-year risk of CVD. Receiver Operating Characteristic (ROC) curve, linear/logistic regression models and Spearman's correlations were used. Results: Intricate associations were found between CK18, FLI and CVD risk scores. While M30 was the only independent predictor of FLI≥60, M65 discriminated best NAFLD individuals at very-high 10-years CVD risk according to SCORE2 (AUC:0.71; p=0.001). Values above the predefined manufacturer cut-off (400 U/l), were associated with an independent 5-fold increased risk (adjusted odds ratio: 5.44, p=0.01), with negative predictive value of 93%. Conclusions: Confirming that NAFLD is associated with an increased CVD risk, our results point to CK18 M65 as a candidate biomarker to identify NAFLD individuals at low CVD risk in European general population.

Natural killer (NK) cells are part of the innate immune system, protects against pathogens and tumor cells and are the main cell effectors of monoclonal antibodies (mAbs) generating antibody-dependent cell cytotoxicity (ADCC). Hence it is relevant to understand NK physiology and status to investigate the biological effect of mAbs in the clinic. The presence of viral-sculpted NK cell populations has already been described, but the presence of cancer-sculpted NK remains unknown. Cancer induces a broad NK cell dysfunction. We investigated the NK cell population by Uniform Manifold Approximation and Projection (UMAP) embed maps in Hodgkin lymphoma (HL) and acute myeloid leukemia (AML) patients at diagnosis and at least 30 days after treatment, which correlates with tumor cell clearance. The NK lineage largely responded to the tumor by generating antitumor NK cells and renewing the population with a subset of immature NK cells. However, we failed to identify specific “memory-like” subsets. Moreover, in patients in relapse we found essentially the same NK populations that at diagnostic, suggesting that NK cells equally respond to the first or second tumor rise. Finally, previous CMV infection largely affects tumor-associated changes in NK population, but the CMV-associated CD57+NKG2C+ NKs do not appear to play any role in tumor immunity.

The assimilation of Soil Moisture and Ocean Salinity (SMOS) data into the ECMWF (European Centre for Medium Range Weather Forecasts) H-TESSEL (Hydrology revised - Tiled ECMWF Scheme for Surface Exchanges over Land) model is presented. SMOS soil moisture (SM) estimates have been produced specifically by training a neural network with SMOS brightness temperatures as input and H-TESSEL model SM simulations as reference. This can help the assimilation of SMOS information in several ways: (1) the neural network soil moisture (NNSM) data have a similar climatology to the model, (2) no global bias is present with respect to the model even if regional differences can exist. Experiments performing joint data assimilation (DA) of NNSM, 2 metre air temperature and relative humidity or NNSM-only DA are discussed. The resulting SM was evaluated against a large number of in situ measurements of SM obtaining similar results to those of the model with no assimilation, even if significant differences were found from site to site. In addition, atmospheric forecasts initialized with H-TESSEL runs (without DA) or with the analysed SM were compared to measure of the impact of the satellite information. Although, NNSM DA has an overall neutral impact in the forecast in the Tropics, a significant positive impact was found in other areas and periods, especially in regions with limited in situ information. The joint NNSM, T2m and RH2m DA improves the forecast for all the seasons in the Southern Hemisphere. The impact is mostly due to T2m and RH2m, but SMOS NN DA alone also improves the forecast in July- September. In the Northern Hemisphere, the joint NNSM, T2m and RH2m DA improves the forecast in April-September, while NNSM alone has a significant positive effect in July-September. Furthermore, forecasting skill maps show that SMOS NNSM improves the forecast in North America and in Northern Asia for up to 72 hours lead time.

Recent reports suggest that dysregulation of lipid metabolism is a key feature of the most invasive cancers. To identify potential biomarkers of tumor aggressiveness, we compared the proteomes of two experimental models of malignant mesothelioma in rats exhibiting different invasive properties. Quantitative changes between the most invasive, M5-T1, versus the least invasive, F4-T2, first led to a list of 424 proteins. A second step, cross-comparing this list with 433 proteins distinguishing invasive vs non-invasive tumors, led to identifying 88 proteins that specifically increased and 157 that decreased, respectively, characterizing the most aggressive M5-T1 tumor. Among the 15 mitochondrial proteins found in these lists, the very long-chain specific acyl-CoA dehydrogenase, encoded by the Acadvl gene and involved in fatty acid beta oxidation, appeared to play an important role in the metabolic reprogramming of the tumor microenvironment. Immunohistochemical staining of tumor sections confirmed increased expression of Acadvl in the M5-T1 tumor. Finally, the dramatic increase and decrease, observed in 25 and 17 proteins, respectively, suggested the existence of a strong link between mitochondrial events and modifications of the extracellular matrix, immune cell components or other subcellular compartments. These findings highlight some important aspects of the tumor microenvironment changes linked to aggressiveness.

Aggregated alpha-synuclein (-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA), respectively. Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of -synuclein exist, including phosphorylated and nitrated forms. It is unclear which -synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant synuclein PTMs in post-mortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three -synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 PD, 5 MSA, 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 -synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures followed by nY39 -synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 -synuclein in MSA. Quantification of the LB scores revealed that pS129 -synuclein was the dominant and earliest -synuclein PTM followed by nY39 -synuclein, while lower amounts of pSer87 -synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.

Fagonia indica is a perennial plant grown in arid climates and utilised in traditional medicine as a treatment for cancer. Previous research has highlighted potential antineoplastic effects of Fagonia indica against breast cancer cell lines. Despite this, there has been little research demonstrating the potential of an aqueous extract of Fagonia indica against colon cancer. Colon cancer is a leading cause of cancer-related mortality, with drug resistance remaining a barrier to treatment. The aim of the present study was to investigate the cytotoxic mechanisms of Fagonia indica in colon cancer cells, including pathways related to proliferation, angiogenesis and inflammation, and ABC membrane transporters. Treatment with Fagonia indica caused a reduction in cell viability in wild-type and chemotherapy resistant colon cancer. Results indicated a role for Akt/ MAPK signalling as a mechanism of Fagonia indica induced cell death, alongside a reduction in the expression of VEG-F, NK-κB and ICAM-1. RT-PCR demonstrated a reduction in expression of ABCG2/ABCC4 in resistant colon cancers, after treatment with Fagonia indica extract. Further research is required to isolate bioactive compounds of Fagonia indica for use against colon cancer.

The available magnetic field strength for high resolution NMR in persistent superconducting magnets has recently improved from 23.5 to 28 Tesla, increasing the proton resonance frequency from 1 to 1.2 GHz. For magic-angle spinning (MAS) NMR, this is expected to improve resolution, provided the sample preparation results in homogeneous broadening. We compare two-dimensional (2D) proton detected MAS NMR spectra of four membrane proteins at 950 and 1.2 GHz. We find a consistent improvement in resolution that scales superlinearly with the increase in magnetic field for three of the four examples. In 3D and 4D spectra, which are now routinely acquired, this improvement indicates the ability to resolve at least 2 and 2.5 times as many signals, respectively.

We explored the impacts of the remote and return to in-person work periods on sleep and well-being as reported by faculty (n = 22) and non-teaching staff (n=21) with and without disabilities. Our results show that contrary to expectations, the Covid-19 remote teaching/working period resulted in better sleep, as well as greater well-being, than the return to in-person. With respect to sleep, faculty members had slightly more negative outcomes than staff, most evident in heightened anxiety and work aspects. Faculty with disabilities had somewhat worse sleep and well-being during the remote period than faculty without disabilities. During the return to in-person work, both faculty and non-teaching staff reported more negative than positive sleep and well-being outcomes. In particular, during the in-person period faculty members experienced slightly more negative sleep outcomes related to anxiety and work, while staff members experienced slightly more negative sleep outcomes related to the need to commute and lifestyle. Our findings show that there were benefits and disadvantages to both remote and in-person work periods, suggesting a hybrid work schedule should be considered in more detail, particularly as an optional reasonable accommodation for faculty and staff with disabilities. Our study highlights that training to keep faculty abreast of the latest technological innovations, ways to promote work-life balance and steps to remedy classroom size and building ventilation to prevent the spread of disease all need urgent attention.

To compare concentrations of endogenous N-acylethanolamines (NAEs) lipid mediators pal-mitoylethanolamide (PEA), oleoylethanolamide (OEA), and anandamide (AEA) in fresh, decon-taminated, cryopreserved and freeze-dried amniotic membrane (AM) allografts. Thereby deter-mining whether AM's analgesic and anti-inflammatory efficiency related to NAEs persists during storage. The concentrations of NAEs were measured using ultra-high-performance liquid chro-matography-tandem mass spectrometry. Indirect fluorescent immunohistochemistry was used to detect the PEA PPARα receptor. The concentrations of PEA, OEA, and AEA were significantly higher after decontamination. A significant decrease was found in cryopreserved AM compared to decontaminated tissue for PEA but not for OEA and AEA. However, significantly higher val-ues for all NAEs were detected in cryopreserved samples compared to fresh tissue before decon-tamination. The freeze-dried AM had similar values to decontaminated AM with no statistically significant difference. The nuclear staining of PPARα receptor was clearly visible in all specimens. The stability of NAEs in AM after cryopreservation was demonstrated under tissue bank storage conditions. However, a significant decrease, but still higher concentration of PEA compared to fresh not decontaminated tissue was found in cryopreserved, but not frieze-dried AM. Results in-dicate that NAEs persist during storage in levels sufficient for the analgesic and anti-inflammatory effects of AM allografts.

This study examines the behavior of stearic acid (SA) and 12-hydroxystearic acid (12-HSA) aqueous mixtures as a function of temperature and 12-HSA/SA molar ratio (R). Whatever R, the system exhibits a morphological transition at a given threshold temperature, from multilamellar self-assemblies at low temperature towards small micelles at high temperature, as shown by a combination of transmittance measurements, Wide Angle X-ray diffraction (WAXS), small angle neutron scattering (SANS) and differential scanning calorimetry (DSC) experiments. Such transition originates from the melting of the crystallized fatty acids within the lamellar phase. The precise determination of the threshold temperature, which ranges between 20°C and 50°C depending on R, allows for the construction of the whole phase diagram of the system as a function of R. At high temperature the micelles that are formed are oblate for pure SA solutions (R = 0) and prolate for pure 12-HSA solution (R = 1). In the case of mixtures, there is a progressive continuous transition from oblate to prolate shape when increasing R, with micelles that are almost purely spherical for R = 0.33.

Fast-scan cyclic voltammetry (FSCV) is an electrochemical sensing technique that can be used for neurochemical sensing with high spatiotemporal resolution. Carbon fiber microelectrodes (CFMEs) are traditionally used as FSCV sensors. However, CFMEs are prone to electrochemical fouling caused by oxidative byproducts of repeated serotonin (5-HT) exposure, which makes them less suitable as a chronic 5-HT sensor. Our team is developing a boron-doped diamond microelectrode (BDDME) that has previously been shown to be relatively resistant to fouling caused by protein adsorption (biofouling). We sought to determine if the BDDME exhibits resistance to electrochemical fouling, which we explored on electrodes fabricated with either femtosecond laser cutting or physical cleaving. We recorded the oxidation current response after 25 repeated injections of 5-HT in a flow-injection-cell and compared the current drop from the first to the last injection. The 5-HT responses were compared to dopamine (DA), a neurochemical that is known to produce minimal fouling oxidative byproducts and have a stable repeated response. Physical cleaving of the BDDME yielded a reduction in fouling due to 5-HT compared to the CFME and the femtosecond laser cut BDDME. However, the femtosecond laser cut BDDME exhibited a large increase in sensitivity over the cleaved BDDME. An extended stability analysis was conducted for all device types following 5-HT fouling tests. This analysis demonstrated an improvement in the long-term stability of boron doped diamond over CFMEs, as well as a diminishing sensitivity of the laser cut BDDME over time. This work reports the electrochemical fouling performance of the BDDME when it is repeatedly exposed to DA or 5-HT, which informs the development of a chronic, diamond-based electrochemical sensor for long-term neurotransmitter measurements in vivo.

Coral reefs are critical ecosystems globally for marine fauna, biodiversity and through the services they provide to humanity. However, they are significantly threatened by anthropogenic stressors, such as climate change. By combining 9 environmental variables and ecological and health-based thresholds obtained from the available literature, we develop, using fuzzy logic (discontinuous functions), a Coral Reef Stress Exposure Index (CRSEI) for remotely monitoring coral reef exposure to environmental stressors. Our approach capitalises on the abundance of readily available satellite Earth Observation (EO) data available in the Google Earth Engine (GEE) cloud-based geospatial processing platform. CRSEI values from 3157 distinct reefs were generated and mapped across 12 important coral reef ecosystem regions. Quantitative analyses indicated that the index detected significant temporal differences in stress and was, therefore, able to capture historic change at a global scale. We also applied the CRSEI to three case-study reef ecosystems, previously well-monitored for stress and disturbance using other methods. PCA analysis indicated that depth, current, sea surface temperature (SST) and SST anomaly accounted for the greatest contribution to the variance in stress in these three regions. The CRSEI corroborated temporal and spatial differences in stress exposure from known disturbances within these reference regions, in addition to identifying the potential drivers of inter- and intra-region differences in stress, namely depth, degree heating weeks and SST anomaly. We discuss how the index can be further improved in future with site-specific thresholds for each stress variable, and the incorporation of additional variables not currently available in GEE. This index provides an open access tool, built around a free and powerful processing platform, that has broad potential to assist in the regular monitoring of our increasingly imperilled coral reef ecosystems, and, in particular, those that are remote or inaccessible.

Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

The control of air quality in museums or storages is of fundamental interest for the conservation of historic artifacts. The present work reports an example of application of RFID sensors developed in the European project SensMat and dedicated to this issue. The sensors are based on the varia-tion of property of an RFID tag coupled to a sensitive silver thin film exposed to the environment. As it will be described in the paper, such low cost sensors are interrogated by a commercial reader and provide the environmental corrosivity index and thus the presence of pollutants. The selected case study concerns the monitoring of pollution by H2S in a building dedicated to conservation and restoration of archeological and historical woods. The ability of sensors to map spatially the corrosivity within buildings is highlighted.

The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds pro-vide cheap alternatives to genetic manipulation methods. However, existing chemical inhibition methods for HS also interfere with chondroitin sulphate (CS), complicating data interpretation of HS function. Herein, a simple method for the selective inhibition of HS biosynthesis is described. Using endogenous metabolic sugar pathways, Ac4GalNAz produces UDP-GlcNAz, which can target HS synthesis. Cell treatment with Ac4GalNAz resulted in defective chain elongation of the polymer and decreased HS expression. Conversely, no adverse effect on CS production was observed. The inhibition was transient and dose-dependent, affording rescue of HS expression after removal of the unnatural azido sugar. The utility of inhibition is demonstrated in cell culture and in whole or-ganisms, demonstrating that this small molecule can be used as a tool for HS inhibition in biological systems.

The aim of our study was to evaluate the impact of T. gondii status on eosinophils count (PNE), eosinophil to lymphocyte ratio (ELR) and eosinophil to neutrophil to lymphocytes ratio (ENLR) before and after can-nabis cessation in patients with psychiatric disorders. One hundred and eighty-eight patients were includ-ed in the study. T. gondii, PNE, ELR, ENLR, and urinary cannabis were measured at baseline and after 4 weeks of cannabis cessation. Highest PNE (p = .02), ELR (p = .03) and ENLR levels (p = .031) and highest increase of PNE (p = .044), and ENLR (p = .036) levels were found in patients after cannabis cessation only in the Toxo+ group. At four weeks, significant interactions between cannabis and T. gondii status for PNE (p = .038), and for ENLR (p = .043) levels were found, as well as for the evolution between baseline and 4 weeks for ENLR level (p = .049). After cannabis cessation, we found a positive correlation between negative symptoms and PNE levels at 4 weeks in the Toxo+ group. This study shows that the increase of inflammation after cannabis cessation might be modulated by T. gondii seropositivity status in patient after cannabis cessation.

Mindfulness-based interventions (MBIs) have been shown to improve health and well-being in adolescents with chronic illnesses. Because they are most often delivered in person in a group setting, there are several barriers that limit access to MBIs for youth with limited mobility or who cannot access in-person MBIs in their communities. The objective of this study was to determine if eHealth is a viable platform to increase accessibility to MBIs for teens with chronic illnesses. This study reports the qualitative results of a mixed method randomized trial describing the experience of the Mindful Awareness and Resilience Skills for Adolescents (MARS-A) program, an 8-week MBI, delivered either in person or via eHealth. Participants were adolescents between the ages of 13 and 18 with a chronic illness recruited at a tertiary pediatric hospital in Toronto, Canada. Individual semi-structured post-participation audio-video interviews were conducted by a research assistant. A multiple-pass inductive process was used to review interview transcripts and interpret emergent themes from the participants’ lived experiences. Fifteen participants completed post-participation interviews. Four distinct themes emerged from participants in both the in-person and eHealth groups: creation of a safe space, fostering peer support and connection, integration of mindfulness skills into daily life and improved well-being through the application of mindfulness. Results from this study suggest that eHealth may be an acceptable and feasible mode of delivery for MBIs in adolescents with chronic illnesses. EHealth should be considered in future studies as a promising avenue to increase access to MBIs in this population.

We describe the behavior of mixtures of stearic acid (SA) and its hydroxylated counterpart 12-hydroxystearic acid (12-HSA) in aqueous mixtures at room temperature, as function of the 12-HSA/(fatty acid) mole ratio R. The morphologies of the self-assembled aggregates are obtained by a multi-structural approach that combines confocal and cryo-TEM microscopies with Small-Angle Neutron Scattering (SANS) and Wide-Angle X-Rays Scattering (WAXS) measurements, coupled with rheology measurements. Fatty acids are solubilized by an excess of ethanolamine counterions, so that their heads are negatively charged. The behavior is driven by the competition between mixing entropy and enthalpic effects. A clear trend towards partitioning between the two types of fatty acids is observed, presumably driven by the favorable formation of a H-bond network between hydroxyl OH function on the 12th carbon. For all R, the self-assembled structures are locally lamellar, with bilayers composed of crystallized and strongly interdigitated fatty acids. At high R, multi-lamellar tubes are formed, similarly as for pure aqueous solutions of 12-HSA. The doping by a low amount of SA molecules only slightly modify the dimensions of the tubes (radius and length), and slightly decreases the bilayers rigidity. The solutions have a gel-like behavior originating from entanglements between tubes and show a yield stress. At intermediate R, a partial local partitioning occurs between the two types of fatty acids. The tubes coexist in solution with helical ribbons. The two structures possibly merge to form very long snaky objects with straight and curved parts. The rigidity of the bilayers and the rheological behavior of the solutions are very similar to those of the high R case. At low R, local partitioning also occurs, and the architecture of the self-assemblies associates the two morphologies of the pure fatty acids systems, respectively 2-D planar bilayers for SA and the tubes describe above for the 12-HSA molecules: they are facetted objects with planar domains enriched in SA molecules, capped with curved domains enriched in 12-HSA molecules. The rigidity of the bilayers is strongly increased, as well their storage modulus, compared to systems with larger R. The solutions remain however viscous fluids in this regime of low R.