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Abstract Aims Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers shown to be highly predictive of adverse outcomes in these patients. The CORTAHF study builds on both these data and the fact that steroid burst therapy has been shown to be effective in the treatment of respiratory diseases and COVID‐19. Our hypothesis is that in patients with AHF and elevated C‐reactive protein (CRP) levels without symptoms or signs of infection, a 7‐day course of steroid therapy will lead to reduced inflammation and short‐term improvement in quality of life and a reduced risk of worsening HF (WHF) events. Methods and results The study, which is currently ongoing, will include 100 patients with AHF ages 18–85, regardless of ejection fraction, screened within 12 h of presentation. Patients will be included who have NT‐proBNP > 1500 pg/mL and CRP > 20 mg/L at screening. Exclusion criteria include haemodynamic instability and symptoms and signs of infection. After signed consent, eligible patients will be randomized according to a central randomization scheme stratified by centre 1:1 to either treatment once daily for 7 days with 40 mg prednisone orally or to standard care. Patients will be assessed at study day 2, day 4 or at discharge if earlier, and at days 7 and 31 at the hospital; and at day 91 through a telephone follow‐up. The primary endpoint is the change in CRP level from baseline to day 7, estimated from a mixed model for repeated measures (MMRM) including all measured timepoints, in patients without a major protocol violation. Secondary endpoints include the time to the first event of WHF adverse event, readmission for HF, or death through day 91; and changes to day 7 in EQ‐5D visual analogue scale score and utility index. Additional clinical and laboratory measures will be assessed. Conclusions The results of the study will add to the knowledge of the role of inflammation in AHF and potentially inform the design of larger studies with possibly longer duration of anti‐inflammatory therapies in AHF.

Abstract This retrospective cohort study used Taussig Cancer Center’s Myeloma Patient Registry to identify adults with multiple myeloma diagnosed between January 2017-December 2021. Electronic health records data captured time from diagnosis to initial prescription fill for oral antimyeloma medications and initiation of facility administered or oral antimyeloma treatment. We identified 720 patients with a mean age at diagnosis of 67 years ±11; 55% were male, 77% White, 22% Black, 1% other races, covered by private insurance (36%), traditional Medicare (29%), Medicare Advantage (25%), and Medicaid (8.3%). Over a third of patients (37%) resided in an area in the most disadvantaged area deprivation index (ADI) quartile. The median available follow-up was 765 days. Seventy-five percent of the cohort filled an oral antimyeloma medication prescription (excluding corticosteroids), with a median time to fill of 28 days (IQR, 15–61). In the multivariable Cox regression model, Black race (vs. White, adjusted hazard ratio [aHR], 0.61, 95% CI, 0.42–0.87), older age at diagnosis (aHR per 1 year, 0.97, 95% CI, 0.95–0.98), diagnosis during an inpatient admission (aHR, 0.63, 95% CI, 0.43–0.92), and estimated glomerular filtration rate ≤29 ml/min/1.73 m2 (vs. ≥60, aHR, 0.46, 95% CI, 0.29–0.73) were negatively associated with prescription fill for oral antimyeloma medication at 30 days, while insurance type and ADI were not significant predictors.

Abstract The coronavirus disease 19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global health crisis with millions of confirmed cases and related deaths. The main protease (Mpro) of SARS-CoV-2 is crucial for viral replication and presents an attractive target for drug development. Despite the approval of some drugs, the search for effective treatments continues. In this study, we systematically evaluated 342 holo-crystal structures of Mpro to identify optimal conformations for structure-based virtual screening (SBVS). Our analysis revealed limited structural flexibility among the structures. Three docking programs, AutoDock Vina, rDock, and Glide were employed to assess the efficiency of virtual screening, revealing diverse performances across selected Mpro structures. We found that the structures 5RHE, 7DDC, and 7DPU (PDB Ids) consistently displayed the lowest EF, AUC, and BEDROCK scores. Furthermore, these structures demonstrated the worst pose prediction results in all docking programs. Two structural differences contribute to variations in docking performance: the absence of the S1 subsite in 7DDC and 7DPU, and the presence of a subpocket in the S2 subsite of 7DDC, 7DPU, and 5RHE. These findings underscore the importance of selecting appropriate Mpro conformations for SBVS, providing valuable insights for advancing drug discovery efforts.

The mining industry is pivotal in ensuring Armenia's foreign exchange earnings. Therefore, we investigate the role of real exports of companies representing the mining of metal ores industry using quarterly data (2012q1 2023q2) in explaining statistically significant changes in the real GDP in the short run based on the least squares estimation technique. We conclude that significant positive changes in the real GDP are not associated with the increase in the industry's real exports since the growth of the mining of metal ores industry in Armenia mainly reflects the developments in the global commodity market. Hence, we find no evidence of the “multiplier effect.” Based on the findings, we substantiate the main challenges the industry could face and highlight the prospects ahead while meeting the objectives that the Mining Sector Development Strategy (until 2035) defined to ensure the industry's growth and attract new investors.

Extracellular vesicles released by the protozoan parasite Leishmania display immunomodulatory properties towards mammalian immune cells. In this study, we have evaluated the potential of extracellular vesicles derived from the non-pathogenic protozoan Leishmania tarentolae towards the development of a vaccine adjuvant. As a proof of concept, we expressed in L. tarentolae a codon-optimized SARS-CoV-2 Spike protein fused to the L. mexicana secreted acid phosphatase signal peptide in the N-terminal and to a 6×-His stretch in the C-terminal. Extracellular vesicles released by the engineered L. tarentolae were isolated by ultracentrifugation and fast protein liquid chromatography and were characterized via nanoparticle tracking analysis and transmission electron microscopy. The recombinant S protein was present in extracellular vesicles released by L. tarentolae, as determined by Western blot analyses and immunoelectron microscopy. Next, we evaluated the immunomodulatory potential of extracellular vesicles containing the S protein towards bone-marrow-derived macrophages and bone-marrow-derived dendritic cells. Our data show that in bone-marrow-derived dendritic cells, extracellular vesicles containing the S protein induced an increased expression of proinflammatory genes compared to plain extracellular vesicles whereas the opposite was observed in bone-marrow-derived macrophages. These findings reveal the immunomodulatory potential of L. tarentolae extracellular vesicles and provide a proof of concept that they can be used as adjuvant in the context of dendritic cell stimulation.

ABSTRACT: Necrotic enteritis is a devastating disease to poultry caused by the bacterium Clostridium perfringens. As a novel approach to combating poultry necrotic enteritis, we identified and characterized several hundred single domain antibody fragments (or nanobodies) capable of binding either the NetB toxin or the collagen-binding adhesin (CnaA) of C. perfringens. Many of the nanobodies could neutralize the in vitro functions of NetB or CnaA with inhibitory concentrations in the nanomolar range. The nanobodies were also screened for proteolytic stability in an extract derived from gastrointestinal tract fluids of chickens. A collection of 6 nanobodies (4 targeting NetB and 2 targeting CnaA) with high neutralizing activity and high gastrointestinal tract extract stability were expressed and secreted by Pichia pastoris or Bacillus subtilis. Chickens were given a feed with 1 of the 2 nanobody-containing groups: 1) nanobody-containing P. pastoris supernatants that were semi-purified, lyophilized, and enterically coated, or 2) B. subtilis spores from strains containing the nanobody genes. Compared to untreated chickens (23.75% mortality), mortality of chickens receiving feed modified with the P. pastoris and B. subtilis products decreased to 11.25 and 7.5%, respectively. These results offer a new opportunity to improve the control of poultry necrotic enteritis by incorporating highly specific nanobodies or bacteria expressing these nanobodies directly into chicken feed.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune neurological disease characterized by the recurrent appearance of demyelinating lesions and progressive disability. Currently, there are multiple disease-modifying treatments, however, there is a significant need to develop new therapeutic targets, especially for the progressive forms of the disease. This review article provides an overview of the most recent studies aimed at understanding the inflammatory processes that are activated in response to the accumulation of kynurenine pathway (KP) metabolites, which exacerbate an imbalance between immune system cells (e.g., Th1, Th2, and T reg) and promote the release of pro-inflammatory interleukins that modulate different mechanisms: membrane-receptors function; nuclear factors expression; and cellular signals. Together, these alterations trigger cell death mechanisms in brain cells and promote neuron loss and axon demyelination. This hypothesis could represent a remarkable approach for disease-modifying therapies for MS. Here, we also provide a perspective on the repositioning of some already approved drugs involved in other signaling pathways, which could represent new therapeutic strategies for MS treatment.

Muscular dystrophies (MDs) are a heterogeneous group of diseases of genetic origin characterized by progressive skeletal muscle degeneration and weakness. There are several types of MDs, varying in terms of age of onset, severity, and pattern of the affected muscles. However, all of them worsen over time, and many patients will eventually lose their ability to walk. In addition to skeletal muscle effects, patients with MDs may present cardiac and respiratory disorders, generating complications that could lead to death. Interdisciplinary management is required to improve the surveillance and quality of life of patients with an MD. At present, pharmacological therapy is only available for Duchene muscular dystrophy (DMD)—the most common type of MD—and is mainly based on the use of corticosteroids. Other MDs caused by alterations in dystrophin-associated proteins (DAPs) are less frequent but represent an important group within these diseases. Pharmacological alternatives with clinical potential in patients with MDs and other proteins associated with dystrophin have been scarcely explored. This review focuses on drugs and molecules that have shown beneficial effects, mainly in experimental models involving alterations in DAPs. The mechanisms associated with the effects leading to promising results regarding the recovery or maintenance of muscle strength and reduction in fibrosis in the less-common MDs (i.e., with respect to DMD) are explored, and other therapeutic targets that could contribute to maintaining the homeostasis of muscle fibers, involving different pathways, such as calcium regulation, hypertrophy, and maintenance of satellite cell function, are also examined. It is possible that some of the drugs explored here could be used to affordably improve the muscular function of patients until a definitive treatment for MDs is developed.

We describe a case of Baylisascaris procyonis roundworm infection in a child in Washington, USA, with autism spectrum disorder. Environmental assessment confirmed nearby raccoon habitation and B. procyonis eggs. B. procyonis infections should be considered a potential cause of human eosinophilic meningitis, particularly among young children and persons with developmental delays.

El ensayo propone una discusión teórica, que parte del problema de cómo repensar conceptos estéticos, hermenéuticos y semióticos como los de unidad de la obra de arte, identidad hermenéutica y denotación-connotación, desde una perspectiva focalizada en el proceso de recepción artística; sobre todo en el caso de obras que carecen de estructura estable y bien diferenciada por límites precisos. En consecuencia, el objetivo es analizar la operatividad de esos conceptos desde la perspectiva de la recepción, proyectándolos sobre la especificidad semiótica de las prácticas artísticas posmodernas. Para ello, en la introducción se define brevemente dicha categoría no genérica y se argumenta su pertinencia metodológica en contraposición a la vaga estrechez que caracteriza a la noción al uso de “artes visuales”. La exposición teórica se divide en dos apartados. En el primero se tratan las nociones de identidad hermenéutica y unidad de la obra de arte, con base en la hermenéutica de Gadamer. En el segundo apartado se analiza el problema de la denotación y la connotación en las prácticas artísticas posmodernas desde una perspectiva semiótica. Se concluye que la identidad hermenéutica de una obra es producida por la comprensión que de ella realizan los receptores; lo cual resulta mucho más evidente en aquellas prácticas artísticas ante las que el receptor se ve precisado a articular, a nivel puramente mental, su propia proyección de significados denotados y connotados, para así poder comprender la obra.

This report aims to show the results of the second excavation campaign at Dvin/Dabīl (Armenia), conducted by the Italian-Armenian research group in Autumn 2022. The excavations involved three areas in distinct sectors of the city: the southern portion of the Lower Fortress, where the 2021 square was deepened and enlarged; the so-called ‘Market’ area, where the 2021 excavations were expanded and a micro-stratigraphic trench was opened; the area southeast of the central district, where an exploratory trench was dug to investigate the archaeological evidence at the site of the future building of the Dvin Museum. Additionally, the last paragraph shows the chemical analysis of pottery samples carried out between 2021 and 2022.

IntroductionThe Eidolon helvum fruit bat is one of the most widely distributed fruit bats in Africa and known to be a reservoir for several pathogenic viruses that can cause disease in animals and humans. To assess the risk of zoonotic spillover, we conducted a serological survey of 304 serum samples from E. helvum bats that were captured for human consumption in Makurdi, Nigeria.MethodsUsing pseudotyped viruses, we screened 304 serum samples for neutralizing antibodies against viruses from the Coronaviridae, Filoviridae, Orthomyxoviridae and Paramyxoviridae families.ResultsWe report the presence of neutralizing antibodies against henipavirus lineage GH-M74a virus (odds ratio 6.23; p

Environmental pollution caused by petroleum-derived plastics continues to increase annually. Consequently, current research is interested in the search for eco-friendly bacterial polymers. The importance of Bacillus bacteria as producers of polyhydroxyalkanoates (PHAs) has been recognized because of their physiological and genetic qualities. In this study, twenty strains of Bacillus genus PHA producers were isolated. Production was initially evaluated qualitatively to screen the strains, and subsequently, the strain B12 or Bacillus sp. 12GS, with the highest production, was selected through liquid fermentation. Biochemical and molecular identification revealed it as a novel isolate of Bacillus cereus. Production optimization was carried out using the Taguchi methodology, determining the optimal parameters as 30 °C, pH 8, 150 rpm, and 4% inoculum, resulting in 87% and 1.91 g/L of polyhydroxybutyrate (PHB). Kinetic studies demonstrated a higher production within 48 h. The produced biopolymer was analyzed using Fourier-transform infrared spectroscopy (FTIR), confirming the production of short-chain-length (scl) polyhydroxyalkanoate, named PHB, and differential scanning calorimetry (DSC) analysis revealed thermal properties, making it a promising material for various applications. The novel B. cereus isolate exhibited a high %PHB, emphasizing the importance of bioprospecting, study, and characterization for strains with biotechnological potential.

Oral bone defects occur as a result of trauma, cancer, infections, periodontal diseases, and caries. Autogenic and allogenic grafts are the gold standard used to treat and regenerate damaged or defective bone segments. However, these materials do not possess the antimicrobial properties necessary to inhibit the invasion of the numerous deleterious pathogens present in the oral microbiota. In the present study, poly(ε-caprolactone) (PCL), nano-hydroxyapatite (nHAp), and a commercial extract of Humulus lupulus L. (hops) were electrospun into polymeric matrices to assess their potential for drug delivery and bone regeneration. The fabricated matrices were analyzed using scanning electron microscopy (SEM), tensile analysis, thermogravimetric analysis (TGA), FTIR assay, and in vitro hydrolytic degradation. The antimicrobial properties were evaluated against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. The cytocompatibility was proved using the MTT assay. SEM analysis established the nanostructured matrices present in the three-dimensional interconnected network. The present research provides new information about the interaction of natural compounds with ceramic and polymeric biomaterials. The hop extract and other natural or synthetic medicinal agents can be effectively loaded into PCL fibers and have the potential to be used in oral applications.

The quest for microbial cellulases has intensified as a response to global challenges in biofuel production. The efficient deconstruction of lignocellulosic biomass holds promise for generating valuable products in various industries such as food, textile, and detergents. This article presents a systematic bioprospection aimed at isolating actinomycetes with exceptional cellulose deconstruction capabilities. Our methodology explored the biodiverse oligotrophic region of Cuatro Cienegas, Coahuila, within the Chihuahuan Desert. Among the evaluated actinomycetes collection, 78% exhibited cellulolytic activity. Through a meticulous screening process based on enzymatic index evaluation, we identified a highly cellulolytic Streptomyces strain for further investigation. Submerged fermentation of this strain revealed an endoglucanase enzymatic activity of 149 U/mg. Genomic analysis of strain Streptomyces sp. STCH565-A revealed unique configurations of carbohydrate-active enzyme (CAZyme) genes, underscoring its potential for lignocellulosic bioconversion applications. These findings not only highlight the significance of the Chihuahuan Desert as a rich source of cellulolytic microorganisms but also offer insights into the systematic exploration and selection of high-performing cellulolytic microorganisms for application in diverse environmental contexts. In conclusion, our bioprospecting study lays a foundation for harnessing the cellulolytic potential of actinomycetes from the Chihuahuan Desert, with implications for advancing cellulose deconstruction processes in various industries. The findings can serve as a blueprint for future bioprospecting efforts in different regions, facilitating the targeted discovery of microorganisms with exceptional cellulosic deconstruction capabilities.

The goal of this study was to examine in-hospital complications in patients with acute ST-elevation myocardial infarction with a different renal function.

The transition from a raw model of development to a creative one, the transformation into a technologically dynamic country capable of developing, producing, and applying high technologies, innovations for large-scale production of competitive goods and services, are considered the most significant components of the strategy for modernizing the economy at the present stage. The study mainly discusses the concept of “creative economy”, its main characteristics, principles, and the international experience of the design economy. Attention is also paid to the consideration of design as a tool and factor in the country’s economic development. The main purpose of writing the article is to study the expanded innovative reproduction system of the economy, to identify its main structural elements. In the last decade, the intensification of globalization, regionalization, modernization and transformation of the economic system has led to a kind of creative development, whose direction and pace are determined by man as an innovator, which increases the relevance of the research topic. The methodological basis of the research was the works of German and other foreign scientists on the problems of economic design. The following research methods were used to perform the tasks: monographic (to study the principles of management of the economic system); system-structural (to study the essence of sustainable economic design); institutional (to study the application of the design problem in institutions); abstract-logical (to make theoretical and methodological generalizations and formulate the results). The main result of the research over time is that the study of the relationship between economics and culture in existing economic models allows for a more in-depth study of the phenomenon of creativity as a factor in innovative processes. The development of research on the role of culture in the formation of human capital can be useful in the study of the main categories of economic development, such as productivity, innovation, creativity. Changes in the focus of cultural economics from the study of cultural heritage and art (welfare model and neoclassical model), as well as a reconsideration of the concept and content of culture, which we observe in these models, can lead to changes in cultural development. Originality/scientific novelty. The scientific novelty of the research consists of its plan and the points that were clarified for the first time. The rationality of the funds allocated by the state for creativity, the inactivity of business in this area, the lack of scientific research, the reduction in the number of researchers and engineers were cited as factors hindering the development of the creative economy. Practical value/implications. The practical significance of the research is related to the fact that the research topic, i.e, the creative economy, affects not only the creation of new products, but also their production methods. For example, practical research has shown that Japan is active in this matter. It was known that Japan was the first country to adopt non-traditional and creative approaches, given the peculiarities of the formation and development of the creative economy. Taking into account the Japanese experience, the use of creative abilities of employees based on physical labor can be applied. Given that Japan is constantly improving technologies, methods, directions, forms, industrial ideas, models and organizations to manage production processes and people, we can consider the possibility of applying this practice in our countries.

Enabling women to be meaningful participants and leaders in rural community-based water and sanitation governance remains a challenge. While the benefits of and barriers to women's participation and leadership have been reported on, there is limited understanding of the role of empowerment in addressing these challenges. To help bridge this knowledge gap, we used a household survey to measure men and women's empowerment in water and sanitation in the rural Tupiza watershed, Bolivia, and key informant interviews with women leaders to identify barriers to leadership. Overall, among survey respondents, fewer men than women were disempowered. Community-level factors, especially those related to comfort in speaking in community meetings and reporting service problems, contributed more to women's disempowerment, as did household-level factors related to work balance and input into decisions about who participates in community water and sanitation activities. Among interviewed community water leaders, many women felt their positions were costly to their households and reported challenges in obtaining technical training and local government assistance, which not only disempowered them as leaders but also was likely tied to poor service delivery and related health outcomes in their communities. We discuss the implications of our findings for rural Bolivia and future research opportunities. HIGHLIGHTS This study is one of the first to assess the relationship between women's empowerment and participation in community-managed water and sanitation.; We measured men's and women's empowerment in water and sanitation and examined the associated barriers to women's successful participation and leadership in rural Bolivia with mixed methods.; Women's discomfort in speaking in community meetings and reporting service problems contributed more to their disempowerment than to men's.; Women leaders' disempowerment was related to their domestic workloads and challenges in obtaining technical training and local government assistance.; By focusing on barriers linked to women's disempowerment, we highlighted the central role of empowerment in improving participation and identified barriers that matter most for gender, water, and sanitation goals.;

We report the identification of 89 new systems containing ultracool dwarf companions to main-sequence stars and white dwarfs, using the citizen science project Backyard Worlds: Planet 9 and cross-reference between Gaia and CatWISE2020. 32 of these companions and 33 host stars were followed up with spectroscopic observations, with companion spectral types ranging from M7–T9 and host spectral types ranging from G2–M9. These systems exhibit diverse characteristics, from young to old ages, blue to very red spectral morphologies, potential membership to known young moving groups, and evidence of spectral binarity in nine companions. 20 of the host stars in our sample show evidence for higher-order multiplicity, with an additional 11 host stars being resolved binaries themselves. We compare this sample’s characteristics with those of the known stellar binary and exoplanet populations, and find our sample begins to fill in the gap between directly imaged exoplanets and stellar binaries on mass ratio–binding energy plots. With this study, we increase the population of ultracool dwarf companions to FGK stars by ∼42%, and more than triple the known population of ultracool dwarf companions with separations larger than 1000 au, providing excellent targets for future atmospheric retrievals.

A complete accounting of nearby objects—from the highest-mass white dwarf progenitors down to low-mass brown dwarfs—is now possible, thanks to an almost complete set of trigonometric parallax determinations from Gaia, ground-based surveys, and Spitzer follow-up. We create a census of objects within a Sun-centered sphere of 20 pc radius and check published literature to decompose each binary or higher-order system into its separate components. The result is a volume-limited census of ∼3600 individual star formation products useful in measuring the initial mass function across the stellar (

Recent unprecedented events worldwide, such as floods in Dubai, recurring heavy rainfall in Santo Domingo, and abrupt temperature changes in the United Kingdom (UK), underscore the tangible impacts of climate change. In response to escalating threats from natural disasters, global communities prioritise resilience and effective disaster management systems. This paper addresses best practices for managing abnormal floods, laying the foundation for the next generation of preparedness and mitigation plans. Focusing on flood risk in Santo Domingo, the study employs the Community Disaster Resilience Framework, conducting a workshop with over 100 stakeholders from government, private, and academic sectors. The assessment spans physical, economic, environmental, and social aspects, revealing common challenges in infrastructure upkeep, public awareness, urban planning, drainage, and economic disparities. The paper proposes technological solutions like predictive maintenance and smart drainage systems, emphasising the potential for implementation. Recognising the importance of community involvement and preparedness, insights from the United Kingdom guide initial steps in strategy development. The conclusions advocate for collaborative efforts among government, academia, and society to navigate the complexities of disaster management and community resilience, ultimately proposing a framework to address these challenges. Further research is suggested in expanding online platforms for disaster risk reduction education in the Caribbean region.

Nucleic acid sensing is a 3 decades old but still challenging area of application for different biological sub-domains, from pathogen detection to single cell transcriptomics analysis. The many applications of nucleic acid detection and identification are mostly carried out by PCR techniques, sequencing, and their derivatives used at large scale. However, these methods’ limitations on speed, cost, complexity and specificity have motivated the development of innovative detection methods among which nucleic acid biosensing technologies seem promising. Toehold switches are a particular class of RNA sensing devices relying on a conformational switch of secondary structure induced by the pairing of the detected trigger RNA with a de novo designed synthetic sensing mRNA molecule. Here we describe a streamlined methodology enabling the development of such a sensor for the RNA-mediated detection of an endangered plant species in a cell-free reaction system. We applied this methodology to help identify the rosewood Dalbergia maritima, a highly trafficked wood, whose protection is limited by the capacity of the authorities to distinguish protected logs from other unprotected but related species. The streamlined pipeline presented in this work is a versatile framework enabling cheap and rapid development of new sensors for custom RNA detection.

Abstract Background Sub-Saharan Africa has seen substantial reductions in cases and deaths due to malaria over the past two decades. While this reduction is primarily due to an increasing expansion of interventions, urbanisation has played its part as urban areas typically experience substantially less malaria transmission than rural areas. However, this may be partially lost with the invasion and establishment of Anopheles stephensi. A. stephensi, the primary urban malaria vector in Asia, was first detected in Africa in 2012 in Djibouti and was subsequently identified in Ethiopia in 2016, and later in Sudan and Somalia. In Djibouti, malaria cases have increased 30-fold from 2012 to 2019 though the impact in the wider region remains unclear. Methods Here, we have adapted an existing model of mechanistic malaria transmission to estimate the increase in vector density required to explain the trends in malaria cases seen in Djibouti. To account for the observed plasticity in An. stephensi behaviour, and the unknowns of how it will establish in a novel environment, we sample behavioural parameters in order to account for a wide range of uncertainty. This quantification is then applied to Ethiopia, considering temperature-dependent extrinsic incubation periods, pre-existing vector-control interventions and Plasmodium falciparum prevalence in order to assess the potential impact of An. stephensi establishment on P. falciparum transmission. Following this, we estimate the potential impact of scaling up ITN (insecticide-treated nets)/IRS (indoor residual spraying) and implementing piperonyl butoxide (PBO) ITNs and larval source management, as well as their economic costs. Results We estimate that annual P. falciparum malaria cases could increase by 50% (95% CI 14–90) if no additional interventions are implemented. The implementation of sufficient control measures to reduce malaria transmission to pre-stephensi levels will cost hundreds of millions of USD. Conclusions Substantial heterogeneity across the country is predicted and large increases in vector control interventions could be needed to prevent a major public health emergency.

Abstract Agriculture in Africa is rapidly expanding but with this comes potential disbenefits for the environment and human health. Here, we retrospectively assess whether childhood malaria in sub-Saharan Africa varies across differing agricultural land uses after controlling for socio-economic and environmental confounders. Using a multi-model inference hierarchical modelling framework, we found that rainfed cropland was associated with increased malaria in rural (OR 1.10, CI 1.03–1.18) but not urban areas, while irrigated or post flooding cropland was associated with malaria in urban (OR 1.09, CI 1.00–1.18) but not rural areas. In contrast, although malaria was associated with complete forest cover (OR 1.35, CI 1.24–1.47), the presence of natural vegetation in agricultural lands potentially reduces the odds of malaria depending on rural–urban context. In contrast, no associations with malaria were observed for natural vegetation interspersed with cropland (veg-dominant mosaic). Agricultural expansion through rainfed or irrigated cropland may increase childhood malaria in rural or urban contexts in sub-Saharan Africa but retaining some natural vegetation within croplands could help mitigate this risk and provide environmental co-benefits.

The global concern over antimicrobial resistance (AMR) and its impact on human health is evident, with approximately 4.95 million annual deaths attributed to antibiotic resistance. Regions with inadequate water, sanitation, and hygiene face challenges in responding to AMR threats. Enteric bacteria, particularly E. coli, are common agents linked to AMR-related deaths (23% of cases). Culture-based methods for detecting tetracycline-resistant E. coli may be of practical value for AMR monitoring in limited resource environments. This study evaluated the ColiGlow™ method with tetracycline for classifying tetracycline-resistant E. coli. A total of 61 surface water samples from Kentucky, USA (2020–2022), provided 61 presumed E. coli isolates, of which 28 isolates were obtained from tetracycline-treated media. Species identification and tetracycline resistance evaluation were performed. It was found that 82% of isolates were E. coli, and 18% were other species; 97% were identified as E. coli when using the API20E identification system. The MicroScan system yielded Enterobacter cloacae false positives in 20% of isolates. Adding tetracycline to ColiGlow increased the odds of isolating tetracycline-resistant E. coli 18-fold. Tetracycline-treated samples yielded 100% tetracycline-resistant E. coli when the total E. coli densities were within the enumeration range of the method. ColiGlow with tetracycline shows promise for monitoring tetracycline-resistant E. coli in natural waters and potentially aiding AMR surveillance in resource-limited settings among other environments.

Abstract Background Non-pharmaceutical interventions (NPIs) are a crucial suite of measures to prevent and control infectious disease outbreaks. Despite being particularly important for crisis-affected populations and those living in informal settlements, who typically reside in overcrowded and resource limited settings with inadequate access to healthcare, guidance on NPI implementation rarely takes the specific needs of such populations into account. We therefore conducted a systematic scoping review of the published evidence to describe the landscape of research and identify evidence gaps concerning the acceptability, feasibility, and effectiveness of NPIs among crisis-affected populations and informal settlements. Methods We systematically reviewed peer-reviewed articles published between 1970 and 2020 to collate available evidence on the feasibility, acceptability, and effectiveness of NPIs in crisis-affected populations and informal settlements. We performed quality assessments of each study using a standardised questionnaire. We analysed the data to produce descriptive summaries according to a number of categories: date of publication; geographical region of intervention; typology of crisis, shelter, modes of transmission, NPI, research design; study design; and study quality. Results Our review included 158 studies published in 85 peer-reviewed articles. Most research used low quality study designs. The acceptability, feasibility, and effectiveness of NPIs was highly context dependent. In general, simple and cost-effective interventions such as community-level environmental cleaning and provision of water, sanitation and hygiene services, and distribution of items for personal protection such as insecticide-treated nets, were both highly feasible and acceptable. Logistical, financial, and human resource constraints affected both the implementation and sustainability of measures. Community engagement emerged as a strong factor contributing to the effectiveness of NPIs. Conversely, measures that involve potential restriction on personal liberty such as case isolation and patient care and burial restrictions were found to be less acceptable, despite apparent effectiveness. Conclusions Overall, the evidence base was variable, with substantial knowledge gaps which varied between settings and pathogens. Based on the current landscape, robust evidence-based guidance is not possible, and a research agenda is urgently required that focusses on these specific vulnerable populations. Although implementation of NPIs presents unique practical challenges in these settings, it is critical that such an agenda is put in place, and that the lessons learned from historical and present experiences are documented to build a firm evidence base. Graphical Abstract

Aim. Study the impact of various combinations of comorbid original diseases in patients infected with COVID-19 later on the disease progression and outcomes of the new coronavirus infection. Materials and methods. The ACTIV registry was created on the Eurasian Association of Therapists initiative. 5,808 patients have been included in the registry: men and women with COVID-19 treated at hospital or at home. ClinicalTrials.gov ID NCT04492384. Results. Most patients with COVID-19 have original comorbid diseases (oCDs). Polymorbidity assessed by way of simple counting of oCDs is an independent factor in negative outcomes of COVID-19. Search for most frequent combinations of 2, 3 and 4 oCDs has revealed absolute domination of cardiovascular diseases (all possible variants). The most unfavorable combination of 2 oCDs includes atrial hypertension (AH) and chronic heart failure (CHF). The most unfavorable combination of 3 oCDs includes AH, coronary heart disease (CHD) and CHF; the worst combination of 4 oCDs includes AH, CHD, CHF and diabetes mellitus. Such combinations increased the risk of lethal outcomes 3.963, 4.082 and 4.215 times respectively. Conclusion. Polymorbidity determined by way of simple counting of diseases may be estimated as a factor in the lethal outcome risk in the acute phase of COVID-19 in real practice. Most frequent combinations of 2, 3 and 4 diseases in patients with COVID-19 primarily include cardiovascular diseases (AH, CHD and CHF), diabetes mellitus and obesity. Combinations of such diseases increase the COVID-19 lethal outcome risk.

[This corrects the article DOI: 10.1371/journal.pntd.0009418.].

Abstract The anti-angiogenic effects of bisphosphonates have been hypothesized as one of the major etiologic factors in the development of medication-related osteonecrosis of the jaw (MRONJ), a severe debilitating condition with limited treatment options. This study evaluated the potential of a gelatine-hyaluronic acid hydrogel loaded with the angiogenic growth factor, vascular endothelial growth factor (VEGF), as a local delivery system to aid in maintaining vascularization in a bisphosphonate-treated (Zoledronic Acid) rodent maxillary extraction defect. Healing was assessed four weeks after implantation of the VEGF-hydrogel into extraction sockets. Gross examination and histological assessment showed that total osteonecrosis and inflammatory infiltrate was significantly reduced in the presence of VEGF. Also, total vascularity and specifically neovascularization, was significantly improved in animals that received VEGF hydrogel. Gene expression of vascular, inflammatory and bone specific markers within the defect area were also significantly altered in the presence of VEGF. Furthermore, plasma cytokine levels were assessed to determine the systemic effect of locally delivered VEGF and showed similar outcomes. In conclusion, the use of locally delivered VEGF within healing extraction sockets assists bone healing and prevents MRONJ via a pro-angiogenic and immunomodulatory mechanism.

ABSTRACT Pathogen-specific rewiring of host cell metabolism creates the metabolically adapted microenvironment required for pathogen replication. Here, we investigated the mechanisms governing the modulation of macrophage mitochondrial properties by the vacuolar pathogen Leishmania. We report that induction of oxidative phosphorylation and mitochondrial biogenesis by Leishmania donovani requires the virulence glycolipid lipophosphoglycan, which stimulates the expression of key transcriptional regulators and structural genes associated with the electron transport chain. Leishmania-induced mitochondriogenesis also requires a lipophosphoglycan-independent pathway involving type I interferon (IFN) receptor signaling. The observation that pharmacological induction of mitochondrial biogenesis enables an avirulent lipophosphoglycan-defective L. donovani mutant to survive in macrophages supports the notion that mitochondrial biogenesis contributes to the creation of a metabolically adapted environment propitious to the colonization of host cells by the parasite. This study provides novel insight into the complex mechanism by which Leishmania metacyclic promastigotes alter host cell mitochondrial biogenesis and metabolism during the colonization process. IMPORTANCE To colonize host phagocytes, Leishmania metacyclic promastigotes subvert host defense mechanisms and create a specialized intracellular niche adapted to their replication. This is accomplished through the action of virulence factors, including the surface coat glycoconjugate lipophosphoglycan. In addition, Leishmania induces proliferation of host cell mitochondria as well as metabolic reprogramming of macrophages. These metabolic alterations are crucial to the colonization process of macrophages, as they may provide metabolites required for parasite growth. In this study, we describe a new key role for lipophosphoglycan in the stimulation of oxidative phosphorylation and mitochondrial biogenesis. We also demonstrate that host cell pattern recognition receptors Toll-like receptor 4 (TLR4) and endosomal TLRs mediate these Leishmania-induced alterations of host cell mitochondrial biology, which also require type I IFN signaling. These findings provide new insight into how Leishmania creates a metabolically adapted environment favorable to their replication.

This paper aims to show the preliminary results of the first excavation campaign at Dvin/Dabīl (Armenia), conducted by the Italian-Armenian research group in Autumn 2021. The excavations involved two areas in distinct sectors of the city. While the Armenian team re-opened the investigation in the so-called Market, the Italian group opened a new digging area in the south portion of the citadel, the South Tower area. Preliminary documentation of the material contexts and laboratory analysis of ceramic samples were included in this mission. Chemical analysis of pottery aims to define the origin of the raw materials used and, hopefully, provide some information about the places of production.

The North West Highlands Geopark is probably one of the largest geoparks anywhere, comprising 2000 km2 of remote, mountainous and coastal terrain. It was the first European Geopark to be recognised in Scotland in 2004 and was designated by UNESCO as a Global Geopark in 2015. Since then, it has been very successful in delivering projects to support sustainable community and economic development based on the region’s Geoheritage and giving informative introductions to the geology, wildlife, landscapes, and human heritage of the region. The geological importance resides in the incredible age of the Lewisian rocks, which are some of the most ancient in Europe, and the organic-walled microfossils of the Torridonian rocks, amongst the oldest evidence of life in the continent of Europe, and possibly the oldest evidence of complex (eukaryotic) non-marine life in the world.

Yellow fever virus (YFV) is an arbovirus affecting humans and non-human primates (NHPs) with seasonal transmission. Here Hamlet et al. model the monthly occurrence of YF in humans and NHPs across Brazil and show that seasonality of agriculture is an important predictor of seasonal YF transmission.

Abstract Background Serological testing based on different antibody types are an alternative method being used to diagnose SARS-CoV-2 and has the potential of having higher diagnostic accuracy compared to the current gold standard rRT-PCR. Therefore, the objective of this review was to evaluate the diagnostic accuracy of IgG and IgM based point-of-care (POC) lateral flow immunoassay (LFIA), chemiluminescence enzyme immunoassay (CLIA), fluorescence enzyme-linked immunoassay (FIA) and ELISA systems that detect SARS-CoV-2 antigens. Method A systematic literature search was carried out in PubMed, Medline complete and MedRxiv. Studies evaluating the diagnostic accuracy of serological assays for SARS-CoV-2 were eligible. Study selection and data-extraction were performed by two authors independently. QUADAS-2 checklist tool was used to assess the quality of the studies. The bivariate model and the hierarchical summary receiver operating characteristic curve model were performed to evaluate the diagnostic accuracy of the serological tests. Subgroup meta-analysis was performed to explore the heterogeneity. Results The pooled sensitivity for IgG (n = 17), IgM (n = 16) and IgG-IgM (n = 24) based LFIA tests were 0.5856, 0.4637 and 0.6886, respectively compared to rRT-PCR method. The pooled sensitivity for IgG (n = 9) and IgM (n = 10) based CLIA tests were 0.9311 and 0.8516, respectively compared to rRT-PCR. The pooled sensitivity the IgG (n = 10), IgM (n = 11) and IgG-IgM (n = 5) based ELISA tests were 0.8292, 0.8388 and 0.8531 respectively compared to rRT-PCR. All tests displayed high specificities ranging from 0.9693 to 0.9991. Amongst the evaluated tests, IgG based CLIA expressed the highest sensitivity signifying its accurate detection of the largest proportion of infections identified by rRT-PCR. ELISA and CLIA tests performed better in terms of sensitivity compared to LFIA. IgG based tests performed better compared to IgM except for the ELISA. Conclusions We report that IgG-IgM based ELISA tests have the best overall diagnostic test accuracy. Moreover, irrespective of the method, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody type independently. Given the poor performances of the current LFIA devices, there is a need for more research on the development of highly sensitivity and specific POC LFIA that are adequate for most individual patient applications and attractive for large sero-prevalence studies. Systematic review registration PROSPERO CRD42020179112

Certain CD8 T cell responses are particularly effective at controlling infection, as exemplified by elite control of HIV in individuals harboring HLA-B57. To understand the structural features that contribute to CD8 T cell elite control, we focused on a strongly protective CD8 T cell response directed against a parasite-derived peptide (HF10) presented by an atypical MHC-I molecule, H-2Ld. This response exhibits a focused TCR repertoire dominated by Vβ2, and a representative TCR (TG6) in complex with Ld-HF10 reveals an unusual structure in which both MHC and TCR contribute extensively to peptide specificity, along with a parallel footprint of TCR on its pMHC ligand. The parallel footprint is a common feature of Vβ2-containing TCRs and correlates with an unusual Vα-Vβ interface, CDR loop conformations, and Vβ2-specific germline contacts with peptides. Vβ2 and Ld may represent “specialist” components for antigen recognition that allows for particularly strong and focused T cell responses.

The idea of this paper is to propose research methods designed for strength analysis of composite materials which are widely used in load-carrying structures. It is shown that the strength analysis and study of composite materials are carried out in two directions – considering them as inhomogeneous composite materials, representing a regular multilayer medium of alternating reinforcement layers and a polymer binder, and the study of the issue of structural strength, in which composites are considered as homogeneous elastic orthotropic bodies, to which the theory of elasticity of anisotropic media is applicable. These approaches enables to represent the composites in the form of a continuous medium and use the methods of the theory of elasticity of anisotropic media in calculating the acting stresses, which makes it possible to use the influence of the elements of manufacturing technology on the physical and mechanical characteristics.

Upside-down jellyfish, Cassiopea, are prevalent in warm and shallow parts of the oceans throughout the world. They are unique among jellyfish in that they rest upside down against the substrate and extend their oral arms upwards. This configuration allows them to continually pull water along the substrate, through their oral arms, and up into the water column for feeding, nutrient and gas exchange, and waste removal. Although the hydrodynamics of the pulsation of jellyfish bells has been studied in many contexts, it is not clear how the presence or absence of the substrate alters the bulk flow patterns generated by Cassiopea medusae. In this paper, we use three-dimensional (3D) particle tracking velocimetry and 3D immersed boundary simulations to characterize the flow generated by upside-down jellyfish. In both cases, the oral arms are removed, which allows us to isolate the effect of the substrate. The experimental results are used to validate numerical simulations, and the numerical simulations show that the presence of the substrate enhances the generation of vortices, which in turn augments the upward velocities of the resulting jets. Furthermore, the presence of the substrate creates a flow pattern where the water volume within the bell is ejected with each pulse cycle. These results suggest that the positioning of the upside-down jellyfish such that its bell is pressed against the ocean floor is beneficial for augmenting vertical flow and increasing the volume of water sampled during each pulse.

Abstract Child protection and mental health during conflict intersects with a variety of adverse conflict-related factors, and intervention outcomes in the field are often difficult to predict. Using the casefiles of 376 school children registered in a Mental Health and Psychosocial Support (MHPSS) project in the Northwest governorate of Idleb in Syria, this study aimed to determine (i) the rates of various protection concerns (potential mental health conditions, psychosocial deprivation issues, and social, behavioural and emotional issues) for students enrolled in this project, (ii) whether the rates of any of the protection concerns varied between children and adolescents, or between boys and girls, and (iii) which of the identified demographic and protection sector factors predicted the presence of potential mental health conditions and MHPSS intervention outcomes. MHPSS interventions (including individual MHPSS sessions tailored for children in conflict, resilience building activities, tutoring, peer building activities, community awareness, and other tailored services) were implemented at schools operated by the UK-based organization, Syria Relief. The variables tested included demographic variables of age group (208 children, aged 4–9 years; 168 adolescents, aged 10–14 years) and gender (211 males, 165 females), and 23 protection sector variables including 11 potential mental health problems (anxiety, attention deficit hyperactivity disorder, conduct disorder, autism, epilepsy, motor tics, depression, post-traumatic-stress disorder, social phobia, specific phobia, learning disability), 7 psychosocial deprivation (PSD) variables (war injury, child labour, loss of caregiver, neglect, domestic abuse, displacement, poverty), and 5 social, behavioural and emotional (SBE) variables (low/abnormal socialization, emotional issue, peer issues/being bullied, peer issues/being aggressive, educational decline). Within the sample, 73.7% were found with a probable mental health problem, with 30.6% showing signs of anxiety, 36.2% of depression and 26.6% showing signs of post-traumatic-stress disorder. Additionally, 74.5% of the sample had at least one form of PSD present (42.6% were displaced, 39.6% suffered from abject poverty), and 64.9% had a reported SBE concern. Children were more likely to have a potential mental health concern, especially autism and PTSD, and poor socialization; while adolescents were more likely to engage in child labour, experience abject poverty, exhibit aggressive behaviour, and educational decline. Male gender was associated with child labour and aggressive behaviour while female gender was associated with the presence of potential mental health problems, especially depression, and loss of caregiver, and poor socialisation. Odds ratios (ORs) indicated significant negative impact of the presence of SBE concerns (any), 4.45 (95% CI: 1.68–12.7), emotional issue, 11.02 (95% CI: 2.76–74.49), low/abnormal socialization, 8.37 (95% CI, 2–57.71), and displacement, 2.91 (95% CI, 1.21–7.48) on the child’s mental health. MHPSS intervention outcomes were categorized as case improvement, decline, or incomplete/limited information available; with case improvement noted for 63.6% of the sample, decline noted for 14.4%, and incomplete treatment/limited follow-up noted for 22.1% of the sample. Additional analysis of predictors of treatment success found that child labour was significantly associated with a lack of treatment success, OR 0.24 (95% CI, 0.07–0.92). These findings provide important insights into the complex tailoring needs that protection and MHPSS field projects require.

Reported COVID-19 mortality rates have been relatively low in Syria, but there has been concern about overwhelmed health systems. Here, the authors use community mortality indicators and estimate that

Social distancing policies aiming to reduce COVID-19 transmission have been reflected in reductions in human mobility. Here, the authors show that reduced mobility is correlated with decreased transmission, but that this relationship weakened over time as social distancing measures were relaxed.

Immunomodulatory biomaterials have the potential to stimulate an immune response able to promote constructive and functional tissue remodeling, as opposed to persistent inflammation and scar tissue formation. This study examined the effects of titanium surface modification on integrin expression and concurrent cytokine secretion by adherent macrophages in vitro in an attempt to delineate the molecular events involved in biomaterial-mediated immunomodulation. Non-polarised (M0) and inflammatory polarised (M1) macrophages were cultured on a relatively smooth (machined) titanium surface and two proprietary modified rough titanium surfaces (blasted and fluoride-modified) for 24 h. The physiochemical characteristics of the titanium surfaces were assessed by microscopy and profilometry, while macrophage integrin expression and cytokine secretion were determined using PCR and ELISA, respectively. After 24 h adhesion onto titanium, integrin α1 expression was downregulated in both M0 and M1 cells on all titanium surfaces. Expression of integrins α2, αM, β1 and β2 increased in M0 cells cultured on the machined surface only, whereas in M1 cells, expression of integrins α2, αM and β1 all increased with culture on both the machined and rough titanium surfaces. These results correlated with a cytokine secretory response whereby levels of IL-1β, IL-31 and TNF-α increased significantly in M1 cells cultured on the titanium surfaces. These results show that adherent inflammatory macrophages interact with titanium in a surface-dependent manner such that increased levels of inflammatory cytokines IL-1β, TNF-α and IL-31 secreted by M1 cells were associated with higher expression of integrins α2, αM and β1.

Objectives: In this data collation study, we aimed to provide a comprehensive database describing the epidemic trends and responses during the first wave of coronavirus disease 2019 (COVID-19) throughout the main provinces in China. Methods: From mid-January to March 2020, we extracted publicly available data regarding the spread and control of COVID-19 from 31 provincial health authorities and major media outlets in mainland China. Based on these data, we conducted descriptive analyses of the epidemic in the six most-affected provinces. Results: School closures, travel restrictions, community-level lockdown, and contact tracing were introduced concurrently around late January but subsequent epidemic trends differed among provinces. Compared with Hubei, the other five most-affected provinces reported a lower crude case fatality ratio and proportion of critical and severe hospitalised cases. From March 2020, as the local transmission of COVID-19 declined, switching the focus of measures to the testing and quarantine of inbound travellers may have helped to sustain the control of the epidemic. Conclusions: Aggregated indicators of case notifications and severity distributions are essential for monitoring an epidemic. A publicly available database containing these indicators and information regarding control measures is a useful resource for further research and policy planning in response to the COVID-19 epidemic.

Este artículo científico presenta el trabajo pedagógico e investigativo realizado en los años 2018 y 2019 en una institución pública con niños y niñas de cuarto primaria en la ciudad de Bogotá, Colombia. Su objetivo principal fue recuperar la otredad en los niños y niñas a partir de la memoria del desplazamiento forzado. Desarrollada bajo la estrategia metodológica de la sistematización de experiencias e instalada en el método cualitativo, se busca reconstruir el proceso vivido en el campo investigativo, donde la memoria permite ser mediadora entre unas formas iniciales de comprender lo otro y los cambios de dicha comprensión que se dieron en las niñas y niños participantes. A partir de la observación participante, los círculos de reflexión y del diario de campo, se diseñó una matriz de ordenamiento y reconstrucción, en la cual se registró cronológicamente el proceso con los niños y niñas; las actividades realizadas, logros e inquietudes como maestra investigadora. Esta sirvió como filtro para, posteriormente, registrar los relatos de las niñas y niños en la herramienta bitácora de análisis, en donde emergieron las categorías de análisis y reflexión. Así, se enuncian como principales resultados las transformaciones a nivel del reconocimiento de las víctimas-sobrevivientes por parte del estudiantado, al transitar de la minimización y exclusión, a un reconocimiento de la otredad como un ser humano semejante a sí mismo y sí misma. Igualmente, el reconocimiento entre pares alcanza transformaciones importantes, en tanto los niños y niñas reconocen en su par a una persona digna de ser valorada y respetada; lo que transforma significativamente estas relaciones basadas en el individualismo y la violencia simbólica. Lo anterior reivindica el rol social y político de los maestros y las maestras de la infancia, pues es posible y necesario llevar a cabo propuestas pedagógicas a partir del abordaje de la memoria, en un contexto afectado por la violencia en donde las niñas y los niños están en capacidad de aportar a los escenarios de construcción de paz.

La transición entre las políticas educativas y su aplicación real en las aulas constituye un tema que promueve diferentes e interesantes reflexiones en el campo de la enseñanza de las Ciencias Naturales en Colombia. La discusión sobre los niveles de concreción curricular debe ir más allá de la mera crítica, para convertirse en un factor de reflexión el cual sitúe a la persona educadora en el campo de la producción académica a través del análisis de la teoría y de la reflexión de su práctica pedagógica. En ese marco, el presente artículo pretende escudriñar a nivel teórico algunas concepciones del currículo de Ciencias, su articulación con las políticas nacionales y, problemáticas derivadas de su puesta en funcionamiento. Es así como al inicio se expone una breve reseña histórica del currículo de Ciencias en Colombia, para luego dar lugar a los lineamientos curriculares que operan en la actualidad y desarrollar algunas reflexiones en torno a las implicaciones de estos tránsitos y las tensiones con su puesta en marcha por parte del cuerpo docente. Para finalizar, se analizan algunas situaciones específicas en donde las tensiones entre lo planeado y ejecutado dan pie al planteamiento de una reflexión propositiva en términos de la resolución de las dificultades en la cotidianidad del profesorado.

The use of bioactive materials has become a standard tool in the arsenal of tissue engineering and regenerative medicine applications. Bioactive materials have gained significant attention due to their ability to mimic tissues physically, chemically and mechanically. Although a plethora of both natural and synthetic polymers have been identified, wool-based keratin, which has a natural propensity to self-assemble, is biocompatible, cytocompatible, biodegradable, non-toxic and non-immunogenic, can also diminish the adhesion and growth of bacterial biofilm. Keratin based materials have subsequently been applied in various tissue engineering applications, from wound healing to drug and growth factor delivery to bone regeneration. This review focuses on the key properties of keratin, including porosity and pore size, swelling rate, degradation rate, wettability and mechanical properties responsible for its biofunctional activity, as well as recent advances in keratin-based biomaterials for biomedical applications.

Introduction: The detection of SARS-CoV-2 genetic material from nasopharyngeal swab samples by RT-PCR is the most specific and sensitive way to test suspected cases. However, factors such as the sampling process, the type of hyssop used, and the anatomical area from which the sample is collected can distort the result and cause false negatives. Objective: To evaluate the reliability of CNUERO hyssops for sample collection for the SARS-CoV-2 diagnosis versus IMPROSWAB hyssops. Material and Methods: To study the reliability of hyssops developed in Cuba for swabbing for the COVID-19 diagnosis by comparing them to other hyssops successfully used for this task, 2 swabbing samples were obtained from each patient (136). One of these two samples was taken using the hyssops made in Cuba, while the other was taken using another hyssop imported from Germany. The positive detections obtained with the use of both hyssops were compared using the Fisher’ s exact test. The result of the detection of each hyssop was evaluated and compared using the ROC curve. Results: The use of CNEURO hyssops allowed the detection of 45 out of 59 positive cases, while IMPROSAWAB hyssops detected 52 out of 59 true positive cases. There were no significant differences between positive cases detected with the use of each hyssop. The sensitivity of sample detection using CNEURO hyssops was 76,3 % while the one using IMPROSWAB hyssops was 88,1 %. Hence, there are no significant differences in the detection of cases using these two hyssops. Conclusion: CNEURO hyssops are safe and reliable to be used to take nasopharyngeal samples from COVID-19 patients.

Introduction: The detection of SARS-CoV-2 genetic material from nasopharyngeal swab samples by RT-PCR is the most specific and sensitive way to test suspected cases. However, factors such as the sampling process, the type of hyssop used, and the anatomical area from which the sample is collected can distort the result and cause false negatives. Objective: To evaluate the reliability of CNUERO hyssops for sample collection for the SARS-CoV-2 diagnosis versus IMPROSWAB hyssops. Material and Methods: To study the reliability of hyssops developed in Cuba for swabbing for the COVID-19 diagnosis by comparing them to other hyssops successfully used for this task, 2 swabbing samples were obtained from each patient (136). One of these two samples was taken using the hyssops made in Cuba, while the other was taken using another hyssop imported from Germany. The positive detections obtained with the use of both hyssops were compared using the Fisher’ s exact test. The result of the detection of each hyssop was evaluated and compared using the ROC curve. Results: The use of CNEURO hyssops allowed the detection of 45 out of 59 positive cases, while IMPROSAWAB hyssops detected 52 out of 59 true positive cases. There were no significant differences between positive cases detected with the use of each hyssop. The sensitivity of sample detection using CNEURO hyssops was 76,3 % while the one using IMPROSWAB hyssops was 88,1 %. Hence, there are no significant differences in the detection of cases using these two hyssops. Conclusion: CNEURO hyssops are safe and reliable to be used to take nasopharyngeal samples from COVID-19 patients.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Abstract Background Biomaterial-based bone tissue engineering represents a promising solution to overcome reduced residual bone volume. It has been previously demonstrated that gradient and offset architectures of three-dimensional melt electrowritten poly-caprolactone (PCL) scaffolds could successfully direct osteoblast cells differentiation toward an osteogenic lineage, resulting in mineralization. The aim of this study was therefore to evaluate the in vivo osteoconductive capacity of PCL scaffolds with these different architectures. Methods Five different calcium phosphate (CaP) coated melt electrowritten PCL pore sized scaffolds: 250 μm and 500 μm, 500 μm with 50% fibre offset (offset.50.50), tri layer gradient 250–500-750 μm (grad.250top) and 750–500-250 μm (grad.750top) were implanted into rodent critical-sized calvarial defects. Empty defects were used as a control. After 4 and 8 weeks of healing, the new bone was assessed by micro-computed tomography and immunohistochemistry. Results Significantly more newly formed bone was shown in the grad.250top scaffold 8 weeks post-implantation. Histological investigation also showed that soft tissue was replaced with newly formed bone and fully covered the grad.250top scaffold. While, the bone healing did not happen completely in the 250 μm, offset.50.50 scaffolds and blank calvaria defects following 8 weeks of implantation. Immunohistochemical analysis showed the expression of osteogenic markers was present in all scaffold groups at both time points. The mineralization marker Osteocalcin was detected with the highest intensity in the grad.250top and 500 μm scaffolds. Moreover, the expression of the endothelial markers showed that robust angiogenesis was involved in the repair process. Conclusions These results suggest that the gradient pore size structure provides superior conditions for bone regeneration.