As a result of identity prejudice, certain individuals are at higher risk for conflict and violence when they are in the field. At-risk individuals include minority identities of the following: race/ethnicity, sexual orientation, disability, gender identity, and/or religion. Everyone deserves to conduct fieldwork as safely as possible; therefore, it is paramount for anyone conducting fieldwork to be informed of the increased risk certain populations face when conducting field research and to define informed strategies. Research groups should adhere to best practices to minimize risk for all individuals who go into the field. Here we provide strategies that 1) acknowledge that some individuals encounter dangerous situations in the field due to their identity(ies), and 2) minimize the chance of conflict between and among researchers and other communities present at field sites. The inclusion of this document as a key resource in a research lab, a university department, or any active research or work environment sends a positive signal to at-risk individuals that their professional community acknowledges their risk and is willing to implement actions to ensure their safety. We suggest that this document be made freely available to anyone who is directly or indirectly involved in fieldwork. Supervisors who support the information in this document should publicly commit to promote a diverse and inclusive environment in order to maintain the safety of their researchers.

Mimosa bush (Vachellia farnesiana) is an invasive woody weed widely distributed in Australia. While it can be controlled using several mechanical and chemical techniques, this study evaluated a novel new herbicide delivery mechanism that minimizes the risk of spray drift and potential non-target damage. It was developed by Bioherbicides Australia and involves the implantation of encapsulated granular herbicides into the stem of intact plants or into the stump after cutting off plants close to ground level (cut stumped). Trials were implemented near Moree (NSW, Australia) on intact (two trials) plants and cut stumped (two trials) plants. For each trial, an untreated control plus the conventional basal bark application of a liquid formulation of triclopyr/picloram mixed with diesel was included for comparison. Encapsulated glyphosate, aminopyralid/metsulfuron-methyl, hexazinone and clopyralid were also tested in all trials. In addition, triclopyr/picloram, and metsulfuron-methyl were included in at least one of the whole plant trials. Aminopyralid/metsulfuron-methyl was consistently most effective at controlling intact plants, whilst aminopyralid/metsulfuron-methyl and clopyralid provided highest mortality when applied to cut stumps of mimosa bush. Overall, highest efficacy was achieved on single stemmed plants, but with some further refinement of the technique it should be possible to achieve similar results for multi-stemmed species.

Cardiac development is a complex developmental process that results in the formation of the four-chambered organ from a single linear heart tube. In the early stages of development, the linear heart tube is composed of only two tissue layers, an external myocardium that is internally lined by the endocardium. Subsequently, the proepicardium emerges at the septum transversum and soon thereafter proepicardial cells will migrate into the naked myocardium, leading to the formation of the embryonic epicardium. As cardiac development proceeds, epicardial-derived cells migrate into the subepicardial space and subsequently invade the developing ventricular chambers leading to the contribution of distinct cardiovascular cell types such as the cardiac fibroskeleton and different components of coronary vasculature. At present, the molecular mechanisms that regulate the transitional process from the proepicardium to the embryonic myocardium are largely unexplored. In this study we have implemented an ex vivo proepicardium/septum transversum (PE/ST)-embryonic myocardium explant model and we demonstrated that miR-223, but not miR-195, is capable of modulating PE/ST migration, a process that seems to be mediated by Slug expression. Thus, our study demonstrates for the first time the implication of distinct microRNAs in the PE/ST to embryonic myocardium transition in chicken embryonic hearts.

Seemingly normal tissues progressively become populated by mutant clones over time. Most of these clones bear mutations in well-known cancer genes but only rarely do they transform into cancer. This poses questions on what triggers cancer initiation and what implications somatic variation has for cancer early detection. We analysed recent mutational screens of healthy and cancer-free diseased tissues to compare somatic drivers and the causes of somatic variation across tissues. We then reviewed the mechanisms of clonal expansion and their relationships with age and diseases other than cancer. We finally discussed the relevance of somatic variation for cancer initiation and how it can help or hinder cancer detection and prevention. The extent of somatic variation is highly variable across tissues and depends on intrinsic features, such as tissue architecture and turnover, as well as the exposure to endogenous and exogenous insults. Most somatic mutations driving clone expansion are tissue-specific and inactivate tumour suppressor genes involved in chromatin modification and cell growth signalling. Some of these genes are more frequently mutated in normal tissues than cancer, indicating a context-dependent cancer promoting or protective role. Mutant clones can persist over a long time or disappear rapidly, suggesting that their fitness depends on the dynamic equilibrium with the environment. The disruption of this equilibrium is likely responsible for their transformation into malignant clones and knowing what triggers this process is key for cancer prevention and early detection. Somatic variation should be considered in liquid biopsy, where it may contribute cancer-independent mutations, and in the identification of cancer drivers, since not all mutated genes favouring clonal expansion also drive tumourigenesis. Somatic variation and the factors governing homeostasis of normal tissues should be taken into account when devising strategies for cancer prevention and early detection.

This paper presents the design and implementation of a multichannel bio-impedance spectroscopy system on field programmable gate arrays (FPGA). The proposed system is capable of acquiring multiple signals from multiple bio-impedance sensors, process the data on the FPGA and store the final data in the on-board Memory. The system employs the Digital Automatic Balance Bridge (DABB) method to acquire data from biosensors. The DABB measures initial data of a known impedance to extrapolate the value of the impedance for the device under test. This method offers a simpler design because the balancing of the circuit is done digitally in the FPGA rather than using an external circuit. Calculations of the impedance values for the device under test were done in the processor. The final data is sent to an onboard Flash Memory to be stored for later access. The control unit handles the interfacing and the scheduling between these different modules (Processor, Flash Memory) as well as interfacing to multiple Balance Bridge and multiple biosensors. The system has been simulated successfully and has comparable performance to other FPGA based solutions. The system has a robust design that is capable of handling and interfacing input from multiple biosensors. Data processing and storage is also performed with minimal resources on the FPGA.

The global burden of stroke is still high, particularly in developing countries, with hypertension serves as the main risk factor. Knowledge related to stroke is essential to establish better prevention strategies. This study aimed to identify factors associated with stroke awareness among hypertensive patients in Indonesia. This was a cross-sectional study conducted in five Community Health Centers in Indonesia. We used a standardized questionnaire to asses stroke awareness and the influencing factors. The knowledge on hypertension was assessed using Hypertension Knowledge Level Scale (HK-LS). Multivariate logistic regression analysis was performed to measure factors associated with stroke awareness. A total of 457 hypertensive patients were included. Majority of patients (77.46%) had low stroke awareness. Having higher knowledge on hypertension, higher income, and a history of previous stroke were associated with higher level of stroke awareness (odds ratio [OR] 1.878, 95%CI 1.176-2.999, p 0.008; OR 1.887, 95%CI 1.170-3.045, p 0.009; OR 5.276, 95%CI 2.210-12.594, p<0.001, respectively). This study suggests that knowledge on hypertension, income, and history of previous stroke are factors which may influence the level of stroke awareness. This emphasizes the need to provide better campaign and education program to raise stroke awareness in a community setting.

The hazard and the carcinogenic risks due to the exposure to some potentially toxic elements by the Santiago Island (Cape Verde) population where calculated, considering soil ingestion, inhalation and dermal contact as exposure pathways. The topsoil of Santiago Island is enriched in Co, Cr, Cu, Ni, V, Zn, Mn and Cd to upper crust values. Hazard indices (HI) were calculated for these metals and As exposures, of Santiago Island population and the calculations were performed for children and adults. For children HI are higher than 1 for Co, Cr and Mn. So there is indication of potential non-carcinogenic risk for children, due to the high Co (HI=2.995), Cr (HI=1.329) and Mn (HI=1.126), values in soils. For the other elements and for adults there is no potential non-carcinogenic risk. Cancer risk was calculated for As, Cd, Cr and Ni exposures, for adults and children and the results are always lower than the carcinogenic target risk of 1x10-6, for As, Cd, and Ni. However, cancer risk are higher than the carcinogenic target risk for Cr, for adults. Regarding As, for children the fraction due to Riskingestion represents 51.6%, while Riskinhalation represents 48.0% and Riskdermalcontact represents only 0.4% of total risk. For adults Riskinhalation represents 81.3%, Riskingestion represents 16.6% and Riskdermal contact represents 2.1%. These results reflect the higher daily ingestion dose for children and the higher inhalation rate and higher dermal contact surface for adults. For the other elements and for adults the cancer risk due to Cr, Ni and Cd inhalation is always higher than for children, reflecting the higher inhalation rate for adults.

In this particular historical moment, the increase in mortality for cardiovascular disease in adults, the increase of metabolic diseases linked to overweight and obesity, it is necessary to focus the attention of medical doctors, researchers and policy makers on the promotion of correct lifestyles and prevention. The "prevention" and "cure or treatment" have long been considered distinct strategies, the almost exclusive prerogative of the public health authorities for the preventive aspects and of the clinician for the treatments. This approach has led, and still leads, to very high healthcare costs, without having a significant impact on obesity incidence. The promotion of correct lifestyles in the population and in subjects at risk in the fight against obesity/overweight, to contrast the reduction of physical activity and sedentary lifestyle, to promote the consumption of fruit and vegetables, to the reduction of the excessive consumption of salt as "Strategic lines of intervention" need to be pursued in all western countries. Actually, the preventive actions undertaken were not very effective, especially for the individuals in pediatric age. In this narrative review, based on published data, the critical points for obesity prevention will be discussed focusing on action needed during life from pre-conception to childhood, adulthood and in geriatric age to contrast obesity.

Many young people are reluctant to seek support for mental health concerns and a preference for self-reliance has been identified as a key barrier. Yet, the conceptualisation and measurement of self-reliance is not well understood. This study examines the meaning of self-reliance as it affects young people’s help-seeking, with an emphasis on the role of trust (both in self and in others). 30 Australian young people aged 18-25 years were interviewed. Reflexive thematic analysis, using both inductive and deductive approaches, was used to construct themes about the relationships between trust, self-reliance, and help-seeking for young people. Participants identified that both self-reliance and help-seeking exist on a continuum from insufficient self-reliance to extreme self-reliance and excessive help-seeking to unwillingness to seek help. Trust was a key component of self-reliance, and a balance between trust in self and trust in others is necessary for self-reliance to be adaptive and appropriate help-seeking to occur. To maintain this balance, young people felt that a level of self-awareness was necessary. A high level of trust in self is considered to increase self-reliance, whereas a high level of trust in others increases help-seeking behaviours. Understanding the role of trust in self-reliance informs developmentally appropriate ways to address self-reliance as a barrier to mental health help-seeking for young people.

In this Case Report we analyze the possible causes of the poor health status of a professional Apis mellifera iberiensis apiary located in Gajanejos (Guadalajara, Spain). Several factors that potentially favor colony collapse were identified, including Nosema ceranae infection, alone or in combination with other factors (eg, BQCV and DWV infection), and the accumulation of acaricides commonly used to control Varroa destructor in the beebread (coumaphos and tau-fluvalinate). Based on the levels of residues, the average toxic unit estimated for the apiary, suggests a possible increase in vulnerability to infection by N. ceranae due to the presence of high levels of acaricides. These data highlight the importance of evaluating these factors in future monitoring programs, as well as the need to adopt adequate preventive measures as part of national and international welfare programs aimed at guaranteeing the health and fitness of bees.

The present study aimed to investigate the effects of a 10-week online high-intensity interval training (HIIT) on body composition and aerobic performance in physically sedentary women. A parallel two-group, longitudinal (pre, post) design was used with physical tests performed before (preintervention) and after (postintervention) the 10-week intervention period. A total of for-ty-eight healthy and physically sedentary women were recruited to participate in this study. Par-ticipants were distributed in two groups: The experimental group (EG) with 24 women (n = 24, age 21.21 ± 2.15 years, weight 61.16 ± 8.94 kg, height 163.96 ± 4.87 cm, body mass index body weight 22.69 ± 2.49 kg/m2), and the control group (CG) with another 24 women (n = 24, age 20.50 ± 1.29 years, weight 62.0 ± 6.65 kg, height 163.92 ± 4 .89 cm, body mass index 23.04 ± 1.74 kg/m2). The EG performed an online HIIT program for 10 weeks, while CG continued with their daily life routines. The repeated measures ANCOVA indicated a significant effect in the within-group analysis for weight (p=0.001; d=-0.96), demonstrating a significant decrease in the Experimental Group (EG) while the Control Group (CG) did not show a significant decrease in body mass in-dex (p=0.15; d=-0.11). Regarding maximal oxygen uptake (VO2 max) values, the EG exhibited a significant improvement (p=0.001; d=-1.07), whereas the CG did not demonstrate a significant improvement (p=0.08; d=-0.37). A new within-group analysis with power output (W) revealed that EG significantly improved (p=0.01; d=-0.96), while CG did not show a significant improve-ment in power output (W/kg) (p=0.20; d=-0.11). Lastly, the within-group analysis with Load re-vealed that EG significantly improved (p=0.001; d=-0.50), while CG did not show a significant improvement in Load (p=0.10.; d=-0.10). The present study showed that 10 weeks of HIIT in an online environment during the Covid-19 lockdown significantly improved maximum oxygen consumption, and caused weight loss and a significant decrease in body mass index in physically sedentary women. These results suggest HIIT may be used as a time-efficient strategy to improve body composition and cardio-respiratory fitness in sedentary women.

The outermost layer of the heart, the epicardium, is an essential cell population that contributes, through epithelial-to-mesenchymal transition (EMT), to form different cell types and provide paracrine signals to the developing heart. Despite its quiescent state during adulthood, in response to cardiac injury, adult epicardium reactivates and recapitulates many aspects of embryonic cardiogenesis supporting cardiac tissue remodeling. Thus, the epicardium has been considered as a crucial source of cell progenitors with important contribution to developing and injured heart. Although several studies have provided evidence about cell fate determination in the epicardium, to date it is unclear whether epicardial-derived cells (EPDCs) come from specific, and previously predetermined, epicardial cell subpopulations or if they are derived from a common progenitor. In recent years, different approaches have been used to study cell heterogeneity within the epicardial layer by using different experimental models. However, generated data are still insufficient to understand the complexity of this epithelial layer. In this review, we summarize the previous works supporting the cellular composition, molecular signatures and diversity within the developing and adult epicardium.

Following on from work already carried out in our laboratory on a new biomass-derived green solvent, eucalyptol, we are now turning our attention to sabinene as a new green solvent. Sabinene is also derived from biomass. We have shown that it can be used as such or distilled to synthesize thiazolo[5,4-b]pyridine heterocycles by thermal or microwave activation. This new solvent was compared with various conventional and green solvents. The conditions were optimized to enable us to carry out the syntheses in good yields, and we were able to show that sabinene, a natural bicyclic monoterpene, could be used effectively as a solvent.

Polymeric microparticles of polyethyleneglycol-polylactic acid-co-glycolic acid (PEG-PLGA) are widely used as drug carriers for a variety of applications due to their unique characteristics. Herein, we developed a novel method for the synthesis of uniformly sized microparticles via coaxial flow-phase separation. The study evaluated the effect of various process parameters on microparticle size and polydispersity including polymer concentration, stirring rate, surfactant concentration, and the organic/aqueous phase flow rate and volume ratio. The results demonstrated that stirring rate and polymer concentration had the most significant impact on the mean particle size and distribution whereas surfactant concentration had the most substantial impact on the morphology of particles. Several microparticle formulations yielding particle sizes in the range of (5-50 µm), morphology, and concentration were synthesized as a demonstration of the tunability and scalability of this method. Notably, by controlling the process parameters microparticles of less than ~ 7 μm could be made using polymer concentrations varying by an order of magnitude. Finally, we demonstrated the tunability and scalability of this method by showing a 10-fold increase in encapsulation efficiency, a 3-fold increase in drug loading of a model hydrophilic drug, and modified release kinetics in microparticle formulations of comparable sizes but different polymer concentrations.

The objective of this work is to study the physical and mechanical behavior of concrete with the addition of 0.5% and 1.0% of coconut fibers subjected to two chemical treatments in order to reduce their degradation and optimize their use in the elaboration of concrete specimens, which must comply with the standards of the American Society for Testing of Materials (ASTM), the American Concrete Institute (ACI) and the Instituto Ecuatoriano de Normalización (INEN). The coconut fibers were obtained from the raw material by hand and cut to a length of 4 cm. Subsequently, the coconut fibers were subjected to two chemical treatments: The first treatment is the immersion of the coconut fibers in 4% sodium hydroxide (NaOH) solution and the second treatment, the coconut fibers were immersed in gum arabic to consequently coat them with silica fume. A particular dosage was carried out with a proportion of 0.5% and 1.0% volume of coconut fiber for the two chemical treatments, replacing the volume of coarse aggregate. Simple concrete joists were made without fiber and with the post-treatment coconut fibers, which were subjected to flexural tests. The results indicated that the best chemical treatment is sodium hydroxide with a concentration of 4% and 1.0% coconut fiber for strengths of 210 kg/cm² and 240 kg/cm². In general, the joists with coconut fiber treated with sodium hydroxide outperformed the fibers treated with gum arabic and silica fume.

Illicit drug consumption is posing critical concerns in our society causing health issues, crime-related activities, and the disruption of border trade. The smuggling of illicit drugs urges the development of new tools for rapid on-site identification in cargos. Current methods used by law enforcement officers rely on presumptive color tests and portable spectroscopic techniques. However, these methods sometimes exhibit inaccurate results due to commonly used cutting agents, the colorful nature of the sample or because the drugs are smuggled (hidden or mixed) in common goods. Interestingly, electrochemical sensors can deal with these specific problems. Herein, an electrochemical device is presented that uses affordable screen-printed electrodes for the electrochemical profiling of illicit drugs by square-wave voltammetry (SWV). The identification of the illicit compound is based on the oxidation potential of the analyte. Hence, a library of electrochemical profiles is built upon the analysis of illicit drugs and common cutting agents. This library allows the design of a tailor-made script that enables the identification of each drug through a user-friendly interface (laptop or mobile phone). Importantly, the electrochemical test is compared by analyzing 48 confiscated samples with other portable devices based on Raman and FTIR spectroscopy as well as a laboratory standard method (i.e. gas chromatography – mass spectrometry). Overall, the electrochemical results obtained through the analysis of different samples from confiscated cargos at an end-user site, present a promising alternative to current methods, offering low-cost and rapid testing in the field.

Transcriptional regulation constitutes a key step in gene expression regulation. Myocyte enhancer factor 2C (MEF2C) is a transcription factor of MADS box family involved in the early development of several cell types including muscle cells. Over the last decade a novel layer of complexity modulating gene regulation is emerging as non-coding RNAs have been identified, impacting in both transcriptional and post-transcriptional regulation. microRNAs represent the most studied and abundantly expressed subtype of small non-coding RNAs and their functional role have been widely documented. On the other hand, our knowledge on the transcriptional and post-transcriptional regulatory mechanisms that drive microRNA expression is still incipient. We recently demonstrated that MEF2C is able to transactive the long, but not short, regulatory element upstream of miR-23a-miR-27a-miR-24-2 transcriptional start site. However, MEF2C over-expression and silencing, respectively, displayed distinct effects on each of the miR-23a-miR-27a-miR-24-2 mature cluster members, without affecting pri-miRNA expression levels, supporting thus additional MEF2C-driven regulatory mechanisms. Within this study we demonstrated a complex post-transcriptional regulatory mechanisms directed by MEF2C in the regulation of miR-23a-miR-27a-miR-24-2 cluster members, distinctly involving different domains of the MEF2C transcription factor and the physical interaction with pre-miRNAs and RNA interacting proteins such as Ksrp, HnRNPa3 and Ddx17.

Mexico shows a high prevalence of obesity in children and adolescents. Geographical location and cultural environment could play a role in the promotion of healthy lifestyles in terms of physical activity (PA), sedentary behavior (SB) and nutrition. The purpose of this study was to assess rural and urban differences in body composition (BC), physical fitness (PF), PA and nutritional status of adolescents from the state of Jalisco (Mexico). The study involved 469 students aged 13-17 years (55.0% girls) from 8 high schools. BC was analyzed by bioimpedance, and PF by standardized field tests. Objective measurements of PA and SB were taken in a subsample (n=240). Energy intake (EI) was calculated from two 24h recalls. Rural residents presented a higher prevalence of overweight, waist circumference, trunk fat mass, regional fat free mass and muscle handgrip strength (all p&lt;0.05, ηp2&lt;0.06). Cardiorespiratory fitness was similar among participants, whereas urban adolescents showed higher muscle power, speed-agility and flexibility scores (all p&lt;0.05, ηp2&lt;0.07). Overall lifestyle behavior in urban adolescents was more sedentary (p&lt;0.05, ηp2= 0.11). EI was similar in both locations. In conclusion, urban Mexican adolescents presented a generally higher sedentary behavior and better fitness and fatness profile than their rural peers.

We report the first detection of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from a dog in Connecticut during February 2021. Complete genome sequencing and phylo-genetic analysis of the hCoV-19/USA/CT-CVMDL-Dog-1/2021 (CT_Dog/2021) virus were con-ducted to identify the origin and lineage of the virus. The CT_Dog/2021 virus belonged to the GH/B1.2. genetic lineage and was genetically close to SARS-CoV-2 identified from humans in the U.S. during the winter of 2020-2021. However, it was not related to other SARS-CoV-2 identified from companion animals in the U.S. It contained both D614G in spike and P323L in nsp12 substitutions which have become the dominant mutations in the United States. The continued sporadic detections of SARS-CoV-2 in companion animals warrant public health concerns about their potential to become a new reservoir species of SARS-CoV-2.

Background: Post-Covid condition can reduce activity and quality of life, resulting in a significant socioeconomic and health burden. Understanding its impact on patients' health is important for the development of personalized rehabilitation interventions. An independent association between obesity and post-covid condition was found because of complications and comorbidities. Methods: Sixteen patients with obesity and post-COVID symptoms (i.e., dyspnea, pain, poor sleep quality, muscle fatigue) admitted to the Istituto Auxologico Italiano, Piancavallo (VB), Italy, were recruited for a four-week rehabilitation program including conventional exercise therapy, nutritional intervention, psychological support and whole-body cryostimulation (WBC). Results: All participants attended all sessions of the program. Anthropometric data showed statistically significant changes in weight, waist circumference and body mass index. Biochemical analyses showed significant reductions in lipid and inflammatory profiles. There was a significant improvement in physical performance, reduction in pain and improvement in psychological well-being. Conclusion: A multidisciplinary rehabilitation protocol including WBC designed for patients with obesity and post-covid condition is safe and feasible. The overall improvements demonstrate that multidisciplinary rehabilitation was effective on post COVID patients and suggest that the use of WBC is safe and could play a role as a booster in rehabilitation programs.

The present study focused on the development of gel-based capsules from sodium alginate and different berries fresh juice: chokeberry, sea buckthorn, and blueberry. Obtained through extrusion method, the macrocapsules were added into yoghurt, a well-known and consumed dairy product. In order to establish the changes that can occur into the food product, the samples were tested during 7, respectively 15 days storage in refrigeration conditions. According to the results, the antioxidant activity increased during storage and gels can represent a good option for bioactive substances’ encapsulation. Sensorial analysis performed indicated that consumers are open to consuming yoghurt berries capsules and, according to the results observed into scientific literature, they no longer rejected the product due to bitterness and sourness of sea buckthorn or aronia.

Lupinus mutabilis Sweet (Fabaceae), “tarwi” or “chocho”, is an important grain legume in the Andean region. In Peru, studies on tarwi have been mainly focused on morphological features, however, the have not been molecularly characterized. Currently, it is possible to explore genetic parameters of plants with reliable and modern methods like genotyping-by-sequencing (GBS). We here for the first time used single nucleotide polymorphisms (SNPs) markers to infer the genetic diversity and population structure of 89 accessions of tarwi from nine Andean regions of Peru. A total of 5922 SNPs distributed along all chromosomes of tarwi were identified. STRUCTURE analysis revealed that this crop is grouped into two clusters. A dendrogram was generated using the UPGMA clustering algorithm and, similar to the principal coordinate analysis (PCoA), it showed two groups that correspond to the geographic origin of the tarwi samples. AMOVA showed a reduced variation between clusters (7.59 %) and indicated that variability within populations is 92.41 %. Population divergence (Fst) between clusters 1 and 2 revealed low genetic difference (0.019). We also detected a negative Fis for both populations, demonstrating that, similar to other Lupinus species, tarwi also depends on cross-pollination. SNPs markers were powerful and effective for the genotyping process in this germplasm. We hope that this information is the beginning of the path towards a modern genetic improvement and conservation strategies of this important Andean legume.

The brown pelican (Pelecanus occidentalis) is a species often affected by natural and man-made disasters such as hurricanes and oil spills as well as general human activities; that subsequently receives medical care and rehabilitation. During rehabilitation, blood may be collected for various testing to help with diagnosis, treatment, and monitoring. Reference intervals for this species are limited, dated, and typically from small sample sizes. Seventy one presumed healthy brown pelicans were sampled as a part of their pre-release examination from rehabilitation at the Wildlife Center of Texas after a large volume stranding in December 2014 to January 2015, and various venous analytes were measured to establish updated reference intervals for Brown Pelicans. Fibrinogen was measured via heat precipitation and the Abaxis VSPro equine Fibrinogen cartridge to determine reference intervals, and in an attempt to validate the VSPro for use in avian species. Abaxis VS2 Avian/Reptile Chemistry panel, iSTAT CG4+, and iSTAT Chem8+ results in addition to body condition score, spun PCV, cloacal temperature and fibrinogen were measured. Proposed reference intervals for brown pelicans are presented. Fibrinogen results were not comparable between the gold standard method and the VSPro, indicating that the VSPro is not appropriate for use in brown pelicans.

Objectives: 1) to demonstrate the anti-inflammatory and anabolic effect of Ozone by determining in serum samples the biochemical levels of IL-6 and IGF-1 in knee osteoarthritis (OA) patients in a real world in Rehabilitation Setting; 2) to evaluate clinical effectiveness by Visual Analog Scale (VAS) and WOMAC scale, and biochemical effect by C-reactive protein (CRP), uric acid and erythrocyte sedimentation rate (ESR). Material and methods: 65 patients with knee OA Kellgren Lawrence (KL) grade 2 or more were analyzed in a retrospective observational study. The study run from January 2018 to September 2021. Inclusion criteria: a) patients 18 years or older; b) with knee OA KL 2º or more; c) biochemical analysis before-and-after treatment; d) pain more than 3 on VAS. Exclusion Criteria: a) previous knee surgery; b) favism; c) pregnancy; d) any other disease that originates lack of collaboration for infiltration. Primary Outcome variables: a) IL-6; b) IGF-1 in diabetes mellitus (DM)/obese and non-DM/non-obese patients; both before-and-after Ozone treatment. Secondary Outcome variables: a) CRP, b) ESR, c) uric acid, d) VAS pain, e) WOMAC pain, function and stiffness. Ozone protocol consisted of 4 sessions (once a week) of an intra-articular infiltration of 20 mL (20µg/mL concentration) of a gas mixture of Oxygen-Ozone 95-5% (produced by Ozone generator Ozonosan-α Plus ®). For biochemical evaluation, SNIBE MAGLUMI ™ IL-6 (CLIA) and SNIBE MAGLUMI ™ IGF-1 (CLIA) kits were used. CRP and uric acid were analyzed by Abbott Alinity c kit; and ESR was evaluated by DIESSE VES MATIC CUBE 30. Results: There is a linear correlation between age and OA severity. IL-6 decreased both in DM and non-DM patients and in all OA KL grades (from 2.7 to 1.59 pg/mL). IGF-1 decreased in total group (OA + DM + obesity) from 112.09 to 107.19 ng/mL. When only knee OA patients were analyzed, Ozone improved IGF-1 levels (from 100.17 to 102.03 ng/mL). Ozone decreased CRP, ESR, uric acid, and improved VAS pain, WOMAC pain, function and stiffness (p<0.05). Conclusions: Ozone is a valid option for the management of knee osteoarthritis in real world Rehabilitation Setting, because of its anti-inflammatory, metabolic and anabolic properties. Ozone downregulates pro-inflammatory IL-6 cytokine. Ozone has a metabolic/hypoglycemic effect on obese/diabetic knee osteoarthritis patients by reducing IGF-1. Ozone has an anabolic effect on non-diabetic/non-obese patients by improving IGF-1. Ozone reduces other biomarkers of inflammation (CRP, ESR and uric acid) and improves, pain, function and quality of life.

The aim of this study as to determine the relationship between the factors of demography, comor-bidity, medication, lifestyle, and access to health services related to the QoL of people with hy-pertension and its complications in Sleman Regency, Yogyakarta. The study was conducted in a cross-sectional manner using data from Sleman HDSS (Health and Demographic Surveillance System) from 2015 to 2018 in cycles 3 and 2 with the inclusion criteria of hypertensive patients and their complications aged 25 years or older obtained by using a total sampling of 532 people. Measurement of QoL using Short Form 12v2 2a and 2b questionnaires presented in the Physical Component Summary (PCS) and Mental Component Summary (MCS). Data analysis using Mann-Whitney test and Kruskal Wallis test. The results showed factors related to the QoL in PCS were variables of gender, age, diagnosis of hypertension and its complications, the presence of comorbidities, fatty foods, drug consumption in the last two weeks, while factors related to the mental component (MCS) were education and occupation seen from the p-value <0.05. QoL with hypertension and its complications influence and decrease the physical than the patient's mental condition.

High-penetration of Distributed Energy Resources (DER) in low voltage distribution grids, mainly photovoltaics (PV), might lead to overvoltage in the point of common coupling. Volt-VAr is one of the common control functions for DER power converters used to enhance the stability and the reliability of the voltage in the distribution system and, thus, fulfilling the network operator requirements. In this study, a centralized algorithm will provide local Volt-VAr control parameters to each PV inverter, based on the electrical grid characteristics where each equipment is installed. Since accurate information of grid characteristics is typically not available, the parametrization of the electrical grid is done using power meter data in DER location and a voltage sensitivity matrix. The algorithm has different optimization modes to both minimize voltage deviation and line current. In order to validate the effectiveness of the algorithm and its deployment in real infrastructure, it has been tested in an experimental setup with PV emulators in a set of 5-day tests. Volt-VAr control algorithm successfully adapted its parameters based on grid topology and PV inverter characteristics, achieving a voltage reduction up to 25% of the allowed voltage deviation.

BACKGROUND: From March to April 2020, Spain was the center of the SARS-CoV-2 pandemic, particularly Madrid with approximately 30% of the cases in Spain. The aim of this study is to report the suspected serious adverse drug reactions (SADRs) in COVID-19 patients versus non-COVID-19 patients detected by the prospective pharmacovigilance program based on automatic laboratory signals (ALSs) in the hospital (PPLSH) during that period. We also compared the results with the suspected SADRs detected during the same period for 2019. METHODS: All ALSs that reflected potential SADRs (including neutropenia, pancytopenia, thrombocytopenia, anemia, eosinophilia, leukocytes in cerebrospinal fluid, hepatitis, pancreatitis, acute kidney injury, rhabdomyolysis and hyponatremia were prospectively monitored in hospitalized patients during the study periods. We analyzed the incidence and the distribution of causative drugs for the COVID-19 patients. RESULTS: The incidence rate of SADRs detected in the COVID-19 patients was 760.63 (95% CI 707.89–816.01) per 10,000 patients, 4.75-fold higher than the SADR rate for non-COVID-19 patients (160.15 per 10,000 patients,95% CI 137.09–186.80), and 5.84-fold higher than the SADR rate detected for the same period in 2019 (130.19 per 10,000 patients, 95% CI 109.53–154.36). The most frequently related drugs were tocilizumab (59.84%), dexketoprofen (13.93%), azithromycin (8.43%), lopinavir-ritonavir (7.35%), dexamethasone (7.62%), and chloroquine/hydroxychloroquine (6.91%). CONCLUSIONS: The incidence rate of SADRs detected by the PPSLH in patients with COVID-19 was 4.75-fold higher than that of the non-COVID-19 patients. Caution is recommended when using medications for COVID-19 patients, especially drugs that are hepatotoxic, myotoxic, and those that induce thromboembolic events.

Mesenchymal stem cells (MSCs) have emerged as a promising treatment for inflammatory diseases. It is described that the immunomodulatory effect of MSCs takes place both by direct cell-to-cell contact and by means of soluble factors that leads to an increased accumulation of regulatory immune cells at the sites of inflammation. Similar efficacy of MSCs has been described regardless the route of administration used, the inflammation conditions and the MHC context. These observations arise the question as to whether the migration of the MSCs to the inflamed tissues is a pre-requisite to achieve their beneficial effect. To address this, we examined the biodistribution and the efficacy of intraperitoneal luciferase-expressing human expanded adipose derived stem cells (Luci-eASCs) in a mouse model of colitis. Luci-eASC-infused mice were stratified according to their response to the Luci-eASC treatment. According to the stratification criteria, there was a tendency to increase the bioluminescence signal in the intestine at the expense of a decrease in the bioluminescence signal in the liver in the `responder´ mice. These data thus suggest that the accumulation of the eASCs to the inflamed tissues is beneficial to achieve an optimal modulation of inflammation.

Two novel members of the subfamily Betarhabdovirinae, family Rhabdoviridae, were identified in Brazil. Overall, their genomes have the typical organization 3’-N-P-P3-M-G-L-5’ observed in mono-segmented plant-infecting rhabdoviruses. In aristolochia-associated cytorhabdovirus (AaCV), found in the liana aristolochia (Aristolochia gibertii Hook), an additional short orphan ORF encoding a transmembrane helix was detected between P3 and M. AaCV genome and deduced encoded proteins share the highest identity values, consistently < 60%, with their counterparts of yerba mate chlorosis-associated virus (Cytorhabdovirus flaviyerbamate). The second virus, false jalap virus (FaJV), was detected in the herbaceous plant false jalap (Mirabilis jalapa L.) and represents together with tomato betanucleorhabdovirus 2, originally found in tomato plants in Slovenia, a tentative new species of the genus Betanucleorhabdovirus. FaJV particles accumulate in the peri-nuclear space, and electron-lucent viroplasms were observed in the nuclei of the infected cells. Notably, distinct from typical rhabdoviruses, most virions of AaCV were observed to be non-enclosed within membrane-bounded cavities. Instead, they were frequently seen in close association with surfaces of mitochondria or peroxisomes. Unlike FaJV, AaCV was successfully graft-transmitted to healthy plants of three species of the genus Aristolochia, while mechanical and seed transmission proved unsuccessful for both viruses. Data suggest that these viruses belong to two new tentative species within the subfamily Betarhabdovirinae.

Background: Cardiac development is a complex developmental process. The early cardiac straight tube is composed of an external myocardial layer and an internal endocardial lining. Soon after rightward looping, the embryonic heart becomes externally covered by a new epithelial lining, the embryonic epicardium. A subset of these embryonic epicardial cells migrate and colonize the embryonic myocardium, contributing to distinct cell types. In recent years, our understanding of the molecular mechanisms that govern proepicardium and embryonic epicardium formation has greatly increased. We have recently witnessed a novel layer of complexity governing gene regulation with the discovery of non-coding RNAs. Our laboratory recently identified three distinct lncRNAs, adjacent to the Wt1, Bmp4 and Fgf8 chicken gene loci, with enhanced expression in the proepicardium that are distinctly regulated by Bmp, Fgf and thymosin 4, providing support of their plausible implication in epicardial formation. Methods: Expression of lncRNAs was analyzed in different chicken and mouse tissues as well as their subcellular distribution in chicken proepicardial, epicardial, ventricle explants and in different murine cardiac cell types. lncRNA transcriptional regulation was analyzed by using siRNAs and expression vectors of different transcription factors in chicken and mouse. Antisense oligonucleotides were used to inhibit Gm14014 expression. Cardiac injury was induced ex vivo in mouse ventricle explants by cryoinjury. Furthermore, RT-qPCR, immunocytochemistry, RNA pulldown, Western blot, viability and cell migration assays were conducted to investigate the biological function of Wt1_76127 and Gm14014. Results: We demonstrated that Wt1_76127 in chicken and its evolutionarily conserved homologue Gm14014 in mice are widely distributed in different embryonic and adult tissues and distinctly regulated by cardiac enriched transcription factors, particularly Mef2c and Nkx2.5. Gm14014 is distinctly regulated in mouse ventricular cryoinjury ex vivo models, displaying a negative correlation with epicardial and epithelial to mesenchymal transition markers. Furthermore, silencing assays demonstrated that mouse Gm14014, but not chicken Wt1_76127, is essential for epicardial, but not endocardial or myocardial cell migration. Such process is governed by partnering with Myl9, promoting cytoskeletal remodeling. Conclusion: Our data evidence that Gm14014 plays a pivotal role in epicardial cell migration essential for heart regeneration.

We present an analysis of high-resolution, near-infrared (NIR) spectra relative to the solar transit of Venus of 5-6 June 2012, as observed with the Facility Infrared Spectropolarimeter (FIRS) at the Dunn Solar Telescope in New Mexico. These observations offer the unique opportunity to probe the upper layers (between ∼84 and 150 km in altitude) of a thick, CO2-dominated atmosphere with the transmission spectroscopy technique – a proxy for future studies of highly-irradiated atmospheres of Earth-sized exoplanets. We were able to visually identify absorption lines from the two most abundant CO2 isotopologues, and from the main isotopologue of CO in the retrieved spectrum of Venus. Furthermore, we perform a cross-correlation analysis of the transmission spectrum using transmission templates generated with petitRADTRANS. With the cross-correlation technique, it was possible to confirm detections of both CO2 isotopologues and CO. Additionally, we retrieve a cross-correlation signal for O3 on Venus. We demonstrate the feasibility of high-resolution, ground-based observations to study the chemical inventory of planetary atmospheres, employing techniques commonly used in exoplanet characterization.

This study explores how young people’s mental health was affected by the COVID-19 pandemic using artwork and semi-structured interviews. This is important to understand so that policy and practice professionals can support those affected, prepare, and respond to future crises, and support young people who are isolated and restricted in other contexts. Co-designed participatory art workshops and interviews were conducted with 16–18-year-olds (N = 21) from the London-based Longitudinal cohort Study of Cognition, Adolescents and Mobile Phones (SCAMP). Artworks and interview transcripts were qualitatively co-analysed with young people. From interviews, six themes were identified: adaptation, restriction, change, challenges, overcoming adversity, and lockdown life. From artwork, four themes were identified; trapped, negative mental wellbeing, positive emotions, and technology. Everyday factors such as home environment, relationships, hobbies, habits, and education or work were key determinants of how challenged and restricted participants felt, and their capacity to overcome this. This implies that young people’s mental health services should collaborate with other sectors to address wider life determinants in a holistic way, and that clearer guidance and support in these areas could mitigate the negative mental health impacts of major environmental changes on young people.

Self-enhancement (SE) is often overlooked as a fundamental cognitive ability mediated via the Pre-Frontal Cortex (PFC). Here we present research that establishes the relationship between the PFC, SE, and the potential evolved beneficial mechanisms. Specifically, we believe there is now enough evidence to speculate that SE exists to provide significant benefits and should be considered a normal aspect of the self. Whatever the metabolic or social cost, the upside of SE is great enough that it is a core and fundamental psychological construct. Furthermore, though entirely theoretical, we suggest that a critical reason the PFC has evolved so significantly in Homo sapien is to, in part, sustain SE. We therefore elaborate as to its proximate and ultimate mechanisms.

The COVID-19 pandemic has highlighted the critical need for telehealth and remote patient monitoring in healthcare delivery. Despite the growing use of on-body wearable sensors for continuous monitoring and predicting adverse events, such as hospitalizations or falls, their widespread adoption within the healthcare ecosystem remains a significant challenge. While the pandemic has accelerated the acceptance of these technologies, achieving widespread integration requires their sustained incorporation into routine healthcare practices beyond emergency situations. In this study, we extend the application of our previously developed remote patient monitoring system, originally designed for the geriatric frail population, to COVID-19 patients. Our objective is to assess whether the metrics obtained from this system, which includes physical activity and indoor localization sensors, along with vital sign monitoring, can provide additional insights into the recovery trajectory of individuals affected by COVID-19.

Humanity will soon define a new era for nature – one that seeks to correct decades of underwhelming responses to the global biodiversity crisis. Area-based conservation efforts, which include both protected areas and other effective area-based conservation measures, are likely to extend and diversify. But persistent shortfalls in ecological representation, management effectiveness and measurable biodiversity outcomes diminish the potential role of area-based conservation in stemming biodiversity loss. Here we show how protected area expansion by governments since 2010 has had limited success in increasing biodiversity coverage, and identify four emergent issues that –if addressed – will enhance the performance of area-based conservation post-2020. We close with recommendations for a broad biodiversity agenda that maximises the potential of area-based conservation. Parties to the Convention on Biological Diversity must recognise that area-based conservation primarily focuses on local threats to species and ecosystems, and needs enhanced emphasis on biodiversity outcomes to better track and fund its contribution to global conservation efforts.

Deep brain stimulation (DBS) is currently a promising technique for psychiatric patients with severe and treatment-resistant symptoms. However, the results to date have been quite heterogeneous, and the indications for psychosurgery with DBS remain in an experimental phase. One of the major challenges limiting the advancement of DBS in psychiatric disorders is the lack of objective criteria for diagnosing certain conditions, which are often based more on clinical scales rather than measurable biological markers. Additionally, there is a limited capacity to objectively assess treatment outcomes. This overview examines the literature on the available biomarkers in psychosurgery in relation to DBS, as well as other relevant biomarkers in psychiatry with potential applicability for this treatment modality. There are five types of biomarkers: clinical/behavioral, omic, neuroimaging, electrophysiological, and neurobiochemical. The information provided by each biomarker within these categories is highly variable and may be relevant for diagnosis, response prediction, target selection, program adjustment, etc. A better understanding of biomarkers and their applications would allow DBS in psychosurgery to advance on a more objective basis, guided by the information provided by them and within the context of precision psychiatry.

Objective: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. Design: Systematic umbrella review of existing meta-analyses. Data Sources: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manually searching reference lists from 2009 to June 2023. Inclusion Criteria: Systematic reviews and meta-analyses of cohort, case-control, and/or cross-sectional study designs that evaluated the associations between exposure to ultra-processed foods and adverse health outcomes in humans across the lifespan. Results: The search identified 45 unique pooled analyses, including 13 dose-response and 32 non-dose-response associations (n=9,888,373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health outcome domains spanning cardiometabolic, gastrointestinal, and respiratory conditions, cancer, mental health, and mortality. Based on a pre-specified evidence classification criteria, convincing evidence (Class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease-related mortality (RR: 1.50; 95%CIs: 1.37 to 1.63), type two diabetes (dose-response RR: 1.12; 95%CIs: 1.11 to 1.13), and depressive outcomes (HR: 1.21; 95%CIs: 1.16 to 1.28), as well as higher risks of prevalent anxiety outcomes (OR: 1.48; 95%CIs: 1.37 to 1.59) and combined common mental disorder outcomes (OR: 1.53; 95%CIs: 1.43 to 1.63). Highly suggestive (Class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all-cause mortality (RR: 1.21; 95%CIs: 1.15 to 1.27), heart disease-related mortality (dose-response HR: 1.66; 95%CIs: 1.51 to 1.84), and type two diabetes (OR: 1.40; 95%CIs: 1.23 to 1.59), together with higher risks of prevalent obesity (OR: 1.55; 95%CIs: 1.36 to 1.77), adverse sleep-related outcomes (OR: 1.41; 95%CIs: 1.24 to 1.60), and wheezing (RR: 1.40; 95%CIs: 1.27 to 1.55). Out of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (Class III-IV) and 13 were graded as no evidence (Class V). Using the GRADE framework, 22 pooled analyses were rated as "Low" quality, with 19 rated as "Very Low” and four rated as "Moderate" quality. Conclusions: Higher exposure to ultra-processed food was associated with a greater risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to evaluate the effectiveness of using population-based measures to target and reduce dietary exposure to ultra-processed foods for improved human health. Systematic Review Registration: PROSPERO CRD42023412732.

The snATAC + snRNA platform allows epigenomic profiling of open chromatin and gene expression with single-cell resolution. The most critical assay step is to isolate high-quality nuclei to proceed with droplet-base single nuclei isolation and barcoding. With the increasing popularity of multiomic profiling in various fields, there is a need for optimized and reliable nuclei isolation methods, mainly for human tissue samples. Herein we compared different nuclei isolation methods for cell suspensions, such as peripheral blood mononuclear cells (PBMC, n=18) and a solid tumor type, ovarian cancer (OC) (n=18), derived from debulking surgery. Nuclei morphology and sequencing output parameters were used to evaluate the quality of preparation. Our results show that NP-40 detergent-based nuclei isolation yields better sequencing results than collagenase tissue dissociation for OC, significantly impacting cell identification and analysis. Given the utility of applying such techniques to frozen samples, we also tested frozen preparation and digestion (n=6). A paired comparison between frozen and fresh samples validated the quality of both specimens. Finally, we demonstrate the reproducibility of scRNA and snATAC + snRNA platform, by comparing the gene expression profiling of PBMC. Our results highlight how the choice of nuclei isolation methods is critical for obtaining quality data in multiomic assays. It also shows that the measurement of expression between scRNA and snRNA is comparable and effective for cell type identification.

Emerging evidence suggests that the human vermiform appendix is not a vestigial organ, but rather an immunological organ of biological relevance. It is hypothesised that the appendix acts as a bacterial ‘safe house’ for commensal gut bacteria and facilitates re-inoculation of the colon after disruption through the release of biofilms. To date, no studies have attempted to explore this potential mechanistic function of the appendix. We conducted a pre-post intervention study in adults (n=59) exploring reestablishment of the gut microbiota in those with and without an appendix after colonic disruption via bowel preparation and colonoscopy. Gut microbiota composition was measured one week before and one month after bowel preparation and colonoscopy using 16S rRNA sequencing. We observed between group differences in gut microbiota composition between those with (n=45) and without (n=13) an appendix at baseline. These differences were no longer evident one-month post-procedure, suggesting that this procedure may have ‘reset’ any potential appendix-related differences between groups. Both groups experienced reductions in gut microbiota richness and shifts in beta diversity post-procedure, with greater changes in those without an appendix, and there were five bacterial genera whose re-establishment post-procedure appeared to be moderated by appendicectomy status. This small experimental study provides preliminary evidence of a potential differential reestablishment of the gut microbiota after disruption in those with and without an appendix, warranting further investigation into the potential role of the appendix as a microbial safe house.

Tumor to stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study we proposed to confirm or dismiss the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma &lt;10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients had stroma-rich tumors, 4% stroma-poor tumors and 89.2%tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation of stroma proportion with tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma-tumor interaction has to be further elucidated.

In the frame of the I-MOVE-COVID-19 project, a cohort of 2050 patients admitted in two Spanish reference hospitals between March 2020 and December 2021 was selected, and a range of clinical factors data were collected at admission to assess their impact on the risk COVID-19 severity outcomes through a multivariate adjusted analysis and nomograms. The need for ventilation and ICU admission were found directly associated with a higher mortality risk (OR 6.9 and 3.2, respectively). The clinical predictors of mortality were need for ventilation and ICU, advanced age, neuromuscular disorders, thrombocytopenia, hypoalbuminaemia, dementia, cancer, elevated CPK and neutrophilia (OR between 1.8 and 3.5), whilst the presence of vomiting, sore throat and cough diminished risk of death (OR 0.5, 0.2 and 0.1 respectively). Admission to ICU was predicted by the need for ventilation, abdominal pain and elevated LDH (OR 371.0, 3.6 and 2.2, respectively) as risk factors; otherwise, it was prevented by advanced age (OR 0.5). In turn, the need for ventilation was predicted by low oxygen saturation, elevated LDH and CPK, diabetes, neutrophilia, obesity and elevated GGT (OR between 1.7 and 5.2), whilst prevented by hypertension (OR 0.5). These findings could enhance patient management and strategic interventions to combat COVID-19.

Epirubicin, olaparib and ribociclib are three anti-tumoral molecules currently used in cancer therapy. Since serum levels of these drugs reveal a large inter-individual variability, validation of a fast, simple and reliable analytical method for quantitative determination of these molecules in human serum, with Therapeutic Drug Monitoring (TDM) purposes would be necessary. Papers in literature describe separation, identification and quantitation of the drugs in pharmaceutical formulas and biological matrices. The large majority of these approaches use protein precipitation for sample pre-treatment, followed by LC separation and tandem-mass-spectrometry (MS/MS) detection. We propose an alternative method using Solid Phase Extraction (SPE) with Oasis PRiME HLB® cartridges followed by high-performance liquid chromatography (HPLC) using a C18 (4.6 × 50 mm) column. A gradient mobile phase with 0.1% formic acid/acetonitrile was utilized. MS detection in single ion recording (SIR) mode was employed. A 13-minutes run-time analysis, including column re-equilibration was assessed. Data for all molecules were validated according to ICH Guidelines. Calibration curves for all analytes were linear with correlation coefficient larger than 0.997. Values for precision were less than 6%. The method was applied on serum samples from patients up-taking the drugs, proving its suitability in TDM assisted adjustment of doses in therapy.

In humankind’s endeavor to explore beyond our planet and travel further into space, we are now at the threshold of an era in which it is possible to move to and from low Earth orbit (LEO) with increasing ease and reduced cost. Through the International Space Station (ISS) U.S. National Laboratory, investigators from industry, academia, and government can easily access the unique LEO environment on the ISS to conduct research and development (R&D) activities in ways not possible on Earth. A key advantage of the LEO environment for life sciences research is the ability to conduct experiments in sustained microgravity conditions. The ability to conduct long-term research in microgravity enables opportunities for novel, fundamental studies in tissue engineering and regenerative medicine, including research on stem cell proliferation and differentiation, biofabrication, and disease modeling using microphysiological systems (MPS) that build on prior research using simulated microgravity conditions (Grimm, D., et al. 2018). Over the last decade, space-based research has demonstrated that microgravity informs our knowledge of fundamental biology and accelerates advancements in health care and medical technologies (International Space Station 2019). The benefits provided by conducting biomedical research in LEO may lead to breakthroughs not achievable on Earth. We are now at a transition point, in which nations are changing their approach to space-based R&D. The focus is shifting from government-funded fundamental science toward the expansion of privately funded R&D with terrestrial application and economic value that will drive a robust marketplace for innovation and manufacturing in LEO. Making this long-term transition requires public-private participation and near-term funding to support critical R&D to leverage the benefits of the LEO environment and de-risk space-based research. Studies conducted on the ISS over the past several years have indicated that one area with potential significant economic value and benefit to life on Earth is space-based biomanufacturing, or the use of biological and nonbiological materials to produce commercially relevant biomolecules and biomaterials for use in preclinical, clinical, and therapeutic applications. We must take advantage of the remaining lifetime of the ISS as a valuable LEO platform to demonstrate this economic value and Earth benefit. By facilitating access to the space station, the ISS National Lab is uniquely positioned to enable the R&D necessary to bridge the gap between the initial discovery phase of space-based biomedical research and the development of a sustainable, investment-worthy biomanufacturing market in LEO supported by future commercial platforms. Through a joint effort, the Center for the Advancement of Science in Space (CASIS), which manages the ISS National Lab, and the University of Pittsburgh’s McGowan Institute for Regenerative Medicine brought together thought leaders from around the U.S. for a Biomanufacturing in Space Symposium that consisted of a series of working sessions to review data from past space-based tissue engineering and regenerative medicine research, discuss relevant current space-based R&D in this area, and consider potential future markets to address the questions: What are the most promising opportunities to leverage the ISS to advance space-based biomanufacturing moving forward? What are the current gaps or barriers that, if overcome, could clear pathways toward private investment in LEO as a valued site for research, development, and production activity? And, most importantly: For which opportunities do the most compelling value propositions exist? The goal of the Biomanufacturing in Space Symposium was to help identify the specific areas in which government and industry investment would be most likely to stimulate advancements that overcome barriers. This would lead to a more investment-ready landscape for private interests to enter the market and fuel exponential growth. The symposium was meant to serve as the first step in developing a roadmap to a sustainable market for biomanufacturing in space. The symposium identified and prioritized multiple key R&D opportunities to advance space-based biomanufacturing. These opportunities fall in the areas of disease modeling, stem cells and stem-cell-derived products, and biofabrication. Additionally, symposium participants highlighted the critical need for additional data to help validate and de-risk these opportunities and concluded that approaches such as automation, artificial intelligence (AI), and machine learning will be needed to produce and capture the required data. Symposium participants also came to a consensus that public-private partnerships and funding will be needed to advance the opportunities toward a biomanufacturing marketplace in LEO. This paper will summarize the current state of the science and technology on the ISS and in the fields of tissue engineering and regenerative medicine; provide an overview of biomanufacturing R&D in space to date; review the goals of the Biomanufacturing in Space Symposium; highlight the key commercial opportunities and gaps identified during the symposium; provide information on potential market sizes; and briefly discuss the next steps in developing a roadmap to biomanufacturing in space.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Introduction: The emergency of the SARS-CoV-2 virus spread and its subsequent global pan-demic have raised significant concerns regarding its impact on pregnancy outcomes. This review aims to summarize the emerging data on the risk of preterm delivery in pregnant women infected with SARS-CoV-2. Materials and Methods: A systematic search was conducted from March 2020 to December 2023 using PubMed, following PRISMA guidelines. Studies correlating maternal COVID-19 infection with preterm birth were included. Results: Thirteen studies were analyzed, indicating a higher incidence of preterm birth in SARS-CoV-2 positive pregnant women compared to controls. The average incidence rate of pre-term birth in infected patients was 18.5%, with a median of 12.75%, while non infected women showed an average incidence of preterm birth of 10% with a median of 8.2%. Discussion: Studies suggest an association between SARS-CoV-2 infection during pregnancy and increased risk of preterm birth and cesarean section. Severity of symptoms and underlying comorbidities further elevate this risk. Notably, infections during the third trimester pose the highest risk of preterm birth. Conclusion: Preventing SARS-CoV-2 infection during pregnancy is crucial to mitigate adverse obstetric outcomes. Close monitoring and tailored interventions for infected pregnant women, particularly those in later trimesters and with comorbidities, are imperative to reduce the risk of preterm birth and improve maternal-fetal outcomes.

RNA extraction from human cumulus cells (CCs) is considered challenging due to low cell’s pop-ulation and small cell. The successful gene expression analysis from cumulus cells ultimately de-pends on an excellent concentration of Ribonucleic acid (RNA) yield by an appropriate technique. Our study aims to consolidate appropriate cumulus cell collection method, preparation and ex-traction techniques to ensure a good yield of RNA for better gene expression analysis. From the results obtained, the optimal strategy found involved mechanical denudation without an enzy-matic process, followed by the use of RNA stabilizer prior to RNA extraction. Subsequently, uti-lizing a smaller homogenizer, preferably manual pressure control with filter (Bio-Masher III®) is paramount for a pure and homogenize sample. Subsequently, during RNA extraction, the use of RNeasy micro kit and RNA carriers is recommended. These sample collection, preparation, and extraction techniques yielded an excellent-quality RNA concentration and successful gene expres-sion analysis. We also conducted a systematic review to consolidate our findings with current evidence of RNA extraction technique. Our results added a value as a current strategy for opti-mizing RNA extraction in CCs for experimental studies. Thus, our findings can contribute to for-mulating a better strategy for optimizing the RNA extraction in CCs for transcriptomic studies.

Abstract: The VSI represents a significant advancement in the assessment of gastrointestinal-specific anxiety among patients with Irritable Bowel Syndrome (IBS) and other Chronic Inflammatory Bowel Diseases (IBD). However, an Italian version of the instrument is not yet available for the reference population. This study utilized a national sample of 500 individuals, including healthy controls and patients with Ulcerative Colitis and Crohn's Disease, to test the validity and reliability of the Italian VSI. Using back-translation methodology to ensure translation fidelity, the research applied a questionnaire and the VSI through an online format to 500 participants. Data analysis revealed that the Italian VSI had excellent psychometric properties, demonstrating high internal consistency (Cronbach’s α = 0.95) and construct validity. The scale proved sensitive in detecting significant differences in visceral sensitivity among groups, highlighting its utility as a clinical and research assessment tool. Specifically, the Italian VSI exhibited a unidimensional factorial structure and maintained a strong correlation with other measures of anxiety and the severity of gastrointestinal symptoms, confirming its role in enhancing the understanding and management of IBS and IBD in Italy.

The rapidly increasing adoption of high-resolution accurate-mass methods in analytical laboratories has fueled demand for instruments that combine high performance and reliability with small size and greater ease-of-use. This paper presents the major design principles that are driving the evolution of the hybrid quadrupole-Orbitrap instrument architecture to enable a greater range of applications and users. These principles may be summarized as follows: better usage of physical space and better access for service by means of size reduction of pumping and ion optics; expanded use of technologies from electronics in ion-optical design; flexibility in performance via modularity of design of the hardware and software components; and, harmonization of interfaces with other instruments to facilitate sharing and transferability of analytical workflows. The design of a novel family of hybrid mass spectrometers is described in detail, and performance evaluation is carried out on a wide variety of samples for its three representatives: the Orbitrap Exploris 120, Orbitrap Exploris 240 and Orbitrap Exploris 480 mass spectrometers.The new instrument family is shown to offer compelling potential not only for high-end proteomics and biopharmaceutical applications, but also for screening, trace, targeted and clinical analysis by liquid chromatography/mass spectrometry methods.

Objective: Mechanical bowel preparation is essential for the visualisation of the colon during colonoscopy, and previous studies have identified changes in gut microbiota composition after bowel preparation and colonoscopy. Considering the gut microbiota is increasingly implicated in mood, we aimed to explore the potential impact of this intervention on mood and the microbiota-gut-brain axis. Methods: We conducted a pre-post intervention study, with timepoints of one week before and one month after bowel preparation and colonoscopy, in community-dwelling adults referred for colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores using generalised estimating equations. We also examined changes in average anxiety, stress, and quality of life scores, and faecal microbiota composition and potential function using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and the gut microbiota and conducted post-hoc analyses to explore potential effect modifiers. Key Results: 59 participants were included in the analyses. Depressive symptoms decreased one-month post-procedure compared to baseline (adjusted β=−0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (1.78; 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Changes in gut microbiome composition included reduced alpha diversity, modest effects on beta-diversity, and increases in genera associated with potential health benefits, one-month post-procedure compared to baseline. Increases in the CLR-transformed abundance of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. Conclusions: There is preliminary evidence of a potential mental health effect of bowel preparation and colonoscopy, which may be associated with changes to the gut microbiota. There may also be a differential mental health impact of this procedure for those with and without IBS. Considering the limitations of our study, further research is required to confirm these findings and their clinical relevance.