IL-17 in skin infections and homeostasis.

Interleukin (IL) 17 is a proinflammatory cytokine belonging to a structurally related group of cytokines known as the IL-17 family. It has been profoundly studied for its contribution to the pathology of autoimmune diseases. However, it also plays an important role in homeostasis and the defense against extracellular bacteria and fungi. IL-17 is important for epithelial barriers, including the skin, where some of its cellular targets reside. Most of the research work on IL-17 has focused on its effects in the skin within the context of autoimmune diseases or sterile inflammation, despite also having impact on other skin conditions. In recent years, studies on the role of IL-17 in the defense against skin pathogens and in the maintenance of skin homeostasis mediated by the microbiota have grown in importance. Here we review and discuss the cumulative evidence regarding the main contribution of IL-17 in the maintenance of skin integrity as well as its protective or pathogenic effects during some skin infections.

Influence of implantation strategy in the transition from temporary left ventricular assist device to durable mechanical circulatory support.

BACKGROUND: Bridging from temporary microaxial left ventricular assist device (tLVAD) to durable left ventricular assist device (dLVAD) is playing an increasing role in the treatment of terminally ill heart failure patients. Scant data exits about the best implantation strategy. The aim of this study is to analyze differences in dLVAD implantation technique and effects on patient outcomes. METHODS: Data from 341 patients (19 European centers), between 01/2017 and 10/2022, who underwent bridge to bridge implantation from tLVAD to dLVAD were retrospectively analyzed. The outcomes of the different implantation techniques on cardiopulmonary bypass (CPB), extracorporeal life support (ECLS) or tLVAD were compared. RESULTS: Durable LVAD implantation was performed employing CPB in 70% of cases (n = 238, group 1), ECLS in 11% (n = 38, group 2) and tLVAD in 19% (n = 65, group 3).Baseline characteristics showed no significant differences in age (p = 0.140), BMI (p = 0.388), creatinine (p = 0.659), Meld score (p = 0.190) and rate of dialysis (p = 0.110). Group 3 had significantly less patients with preoperatively invasive ventilation and cardiopulmonary resuscitation before tLVAD implantation (p = 0.009 and p < 0.001 respectively). Concomitant procedures were performed more often in group 1 and 2 compared to group 3 (24%, 37% and 5%, respectively, p < 0.001).The 30-day mortality showed a significant better survival after inverse probability of treatment weighting in group 3, but the 1-year mortality showed no significant differences between groups (p = 0.012 and 0.581, respectively).Post-operative complications like rate of RVAD implantation or re-thoracotomy due to bleeding, post-operative respiratory failure and renal replacement therapy showed no significant differences between groups.Freedom from first adverse event like stroke, driveline infection or pump thrombosis during follow-up was not significantly different between groups.Post-operative blood transfusion within 24-hours were significantly higher in groups 1 and 2 compared to surgery on tLVAD support (p < 0.001 and p = 0.003, respectively). CONCLUSIONS: In our analysis, the transition from tLVAD to dLVAD without further circulatory support did not show a difference in post-operative long-term survival, but a better 30-day survival was reported. The implantation by using only tLVAD showed a reduction in post-operative transfusion rates, right heart failure and the re-thoracotomy rate without increasing the risk of postoperative stroke or pump thrombosis. In this small cohort study, our data supports the hypothesis that we could demonstrate dLVAD implantation on tLVAD is a safe and feasible technique in selected patients.

Rationalisation of the purification process for a phage active pharmaceutical ingredient.

The resurgence of phage therapy, once abandoned in the early 20th century in part due to issues related to the purification process and stability, is spurred by the global threat of antibiotic resistance. Engineering advances have enabled more precise separation unit operations, improving overall purification efficiency. The present review discusses the physicochemical properties of impurities commonly found in a phage lysate, e.g., contaminants, phage-related impurities, and propagation-related impurities. Differences in phages and bacterial impurities properties are leveraged to elaborate a four-step phage purification process: clarification, capture and concentration, subsequent purification and polishing. Ultimately, a framework for rationalising the development of a purification process is proposed, considering three operational characteristics, i.e., scalability, transferability to various phages and duration. This guide facilitates the preselection of a sequence of unit operations, which can then be confronted with the expected impurities to validate the theoretical capacity of the process to purify the phage lysate.

Effect of NiAl alloy microparticles deposited in flexible SERS substrates on the limit of detection of rhodamine B molecules.

Flexible-SERS (FSERS) substrates were fabricated by depositing Ni64Al36(NiAl)-alloy-microparticles and/or spherical Ag-NPs (sizes of 10-40 nm) on recycled plastics, which had an aluminum layer on their surface. First, FSERS substrates made of Al + Ag-NPs and an area of 1 cm2 were used to detect rhodamine B (RhB) molecules. The limit-of-detection (LOD) for RhB was 8.35 × 10-22 moles (∼503 molecules), and the enhancement factor (EF) was 3.11 × 1015. After adding NiAl-microparticles to the substrate, the LOD decreased to 8.35 × 10-24 moles (∼5 molecules) and the EF was increased to 2.05 × 1017. Such EF values were calculated with respect to substrates made only with Al + NiAl-alloy (without Ag-NPs), which did not show any Raman signal. Other FSERS substrates were made with graphene-layer + Ag-NPs or graphene-layer + NiAl-alloy + Ag-Nps, and the best LOD and EF values were 8.35 × 10-22 moles and 6.89 × 1015, respectively. Overall, combining the Ag-NPs and NiAl-alloy microparticles allowed for the zeptomole detection of RhB. This was possible due to the formation of Ag aggregates around the alloy microparticles, which enhanced the number of hotspots. If no alloy is present in the FSERS substrates, the detection of RhB is lowered. Overall, we presented a low-cost FSERS substrate that does not require expensive Au films or Au-NPs (as previously reported) to detect RhB at the zeptomole level.

Field Applications of Fluorinated Nematicides for Meloidogyne enterolobii Management on Tomato.

Mexico is the 8th largest producer of tomatoes. Meloidogyne enterolobii is reported in Sinaloa, affecting tomato cultivars with genetic resistance to Meloidogyne spp. We aimed to evaluate field applications of fluopyram, fluensulfone, and fluazaindolizine treatments for managing M. enterolobii on tomatoes. Experiments were set on raised beds in a shade house. Nematicides were applied via drip irrigation. Under fluopyram treatment, M. enterolobii did not reduce the number of extra-large-size fruits. The number of large-size fruits with fluopyram and fluazaindolizine plus fluopyram treatments was also unaffected by M. enterolobii. Yield from the treatments fluopyram, fluazaindolizine plus fluopyram, and fluensulfone plus fluopyram was similar to the control treatment without M. enterolobii. Finally, fluazaindolizine plus fluopyram, fluopyram, and fluensulfone plus fluopyram treatments showed the highest reduction of root galling. We conclude that the fluopyram was more effective as an individual treatment. Pre-plant applications of fluensulfone and fluazaindolizine reduced the damage to the plant and the loss of yield; however, the complementary application of fluorinated nematicides improved the management of M. enterolobii in the tomato crop.

Acute and chronic mammary periprosthetic histological changes of the muscle.

Background: Augmentation mammoplasty with subpectoral prosthesis implantation is a frequent performed procedure in plastic surgery for reconstructive and aesthetic purposes. Although prosthesis implantation in a pocket under the major pectoralis muscle has been related to volumetric and functional alterations, there is not much information about the associated short- and long-term histological changes. Therefore, the aim of our study was to describe the acute and chronic histological muscle alterations associated with subpectoral prosthesis implantation. Materials and Method: We collected samples from patients with breast tissue expander (<6 months after implantation) and prosthesis (>1 year after implantation) and from patients without implantation as a control group. The samples were processed for assessing their histological, histochemical and immunohistochemical properties. Results: In the control group, no relevant histological findings were identified. Additionally, in the patients with expander, we observed mild augmentation of the internalised nuclei, normal morphology, significant muscle atrophy and fibrosis, whereas in the patients with prosthesis considerable augmentation of internalised nuclei, significant muscle atrophy, fibrosis and alteration of normal muscle morphology were observed. Conclusion: Prosthesis implantation induces histological changes in the periprosthetic striated muscle. Chronic fibrosis and inflammation play key roles in this process, which should be characterised in more detail from the histological and molecular biological perspective.

Boron nitride nanotube peapods at ultrasonic velocity impacts: a fully atomistic molecular dynamics investigation.

Boron nitride nanotube peapods (BNNT-peapod) are composed of linear chains of C60molecules encapsulated inside BNNTs, they were first synthesized in 2003. In this work, we investigated the mechanical response and fracture dynamics of BNNT-peapods under ultrasonic velocity impacts (from 1 km s-1up to 6 km s-1) against a solid target. We carried out fully atomistic reactive molecular dynamics simulations using a reactive force field. We have considered the case of horizontal and vertical shootings. Depending on the velocity values, we observed tube bending, tube fracture, and C60ejection. Furthermore, the nanotube unzips for horizontal impacts at certain speeds, forming bi-layer nanoribbons 'incrusted' with C60molecules. The methodology used here is applicable to other nanostructures. We hope it motivates other theoretical investigations on the behavior of nanostructures at ultrasonic velocity impacts and aid in interpreting future experimental results. It should be stressed that similar experiments and simulations were carried out on carbon nanotubes trying to obtain nanodiamonds. The present study expands these investigations to include BNNT.

A metagenomic-based study of two sites from the Barbadian reef system.

We study the microbiome of sea water collected from two locations of the Barbadian coral reefs. The two sites differ in several environmental and ecological variables including their endogenous benthic community and their proximity to urban development and runoffs from inland watersheds. The composition of the microbial communities was estimated using whole genome DNA shotgun sequencing with adjuvant measurements of chemical and environmental qualities. Although both sites exhibit a similar degree of richness, the less urbanized site (Maycocks reef at Hangman's Bay) has a strong concentration of phototrophs whereas the more urbanized location (Bellairs reef at Folkstone) is enriched for copiotrophs, macroalgal symbionts and marine-related disease-bearing organisms from taxa scattered across the tree of life. Our results are concordant with previous profiles of warm ocean surface waters, suggesting our approach captures the state of each coral reef site, setting the stage for longitudinal studies of marine microbiome dynamics in Barbados. Supplementary Information: The online version contains supplementary material available at 10.1007/s00338-022-02330-y.

Socioeconomic Level and the Relationship in Glycemic Behavior in the Mexican Population. A Nutritional Alternative Focused on Vulnerable Populations.

In this study, numerical approximations were generated to analyze the behavior of glycemic variations in the non-diabetic population of the Mexican republic. The main objective of this work is to obtain an overview of the glycemic variations in the non-diabetic population from different socioeconomic statuses in Mexico (Medium-high, medium, and low). Thus, evaluating the effect on the glucose level under a healthy diet considering the socioeconomic capabilities of the population. Through the national health and nutrition survey of Mexico 2020 and the Mexican food base, 1420 virtual patients were proposed (522 low status, 485 medium status and 413 Medium-High status) focused on simulating the glycemic behavior in each of the survey participants. Considering that the average food expenditure of the Mexican population is $107.00 MXN, and the cost of a healthy diet is $66.50 MXN, the economic sustainability of the Mexican population to adopt a healthy diet is revealed. The particularity of this work is focused on obtaining diverse data that are difficult to access in the development of population analyses. Such is the case of the approach proposed for different socioeconomic statuses. In this way, the proposed methodology provides a framework for complementary research contributions to the subject.

Point pattern analysis and classification on compact two-point homogeneous spaces evolving time.

This paper introduces a new modeling framework for the statistical analysis of point patterns on a manifold Md, defined by a connected and compact two-point homogeneous space, including the special case of the sphere. The presented approach is based on temporal Cox processes driven by a L2(Md)-valued log-intensity. Different aggregation schemes on the manifold of the spatiotemporal point-referenced data are implemented in terms of the time-varying discrete Jacobi polynomial transform of the log-risk process. The n-dimensional microscale point pattern evolution in time at different manifold spatial scales is then characterized from such a transform. The simulation study undertaken illustrates the construction of spherical point process models displaying aggregation at low Legendre polynomial transform frequencies (large scale), while regularity is observed at high frequencies (small scale). K-function analysis supports these results under temporal short, intermediate and long range dependence of the log-risk process.

The synthetic molecule stauprimide impairs cell growth and migration in triple-negative breast cancer.

Stauprimide, a semi-synthetic derivative of staurosporine, is known mainly for its potent differentiation-enhancing properties in embryonic stem cells. Here, we studied the effects of stauprimide in cell growth and migration of triple-negative breast cancer cells in vitro, evaluating its potential antitumoral activity in an orthotopic mouse model of breast cancer in vivo. Our results from survival curves, EdU incorporation, cell cycle analysis and annexin-V detection in MDA-MB-231 cells indicated that stauprimide inhibited cell proliferation, arresting cell cycle in G2/M without induction of apoptosis. A decrease in the migratory capability of MDA-MB-231 was also assessed in response to stauprimide. In this work we pointed to a mechanism of action of stauprimide involving the modulation of ERK1/2, Akt and p38 MAPK signalling pathways, and the downregulation of MYC in MDA-MB-231 cells. In addition, orthotopic MDA-MB-231 xenograft and 4T1 syngeneic models suggested an effect of stauprimide in vivo, increasing the necrotic core of tumors and reducing metastasis in lung and liver of mice. Together, our results point to the promising role of stauprimide as a putative therapeutic agent in triple-negative breast cancer.

[Analysis of the impact of COVID-19 on youngsters with autistic spectrum disorder]. / Análisis del impacto de la COVID-19 en menores de edad con trastorno del espectro autista.

INTRODUCTION: The state of emergency and national lockdown declared in Spain over the coronavirus pandemic markedly impaired routines and access towards health services supports for children with Autism Spectrum Disorder (ASD). This population is of particular vulnerability towards sudden changes and is distinguished by their complex management. OBJECTIVES: The main goal was to qualitatively assess the psychosocial and mental state of children diagnosed with ASD affiliated to the Hospital Clinic de Barcelona, during and after the first lockdown period. PATIENTS AND METHODS: A survey was administered to relatives of 65 boys and girls with a main diagnosis of ASD. RESULTS: A worsening of key A symptoms was reported during lockdown. In addition, the use of new technologies, intake between meals, and anxiety symptoms increased. Recovery after lockdown was not complete in our sample. CONCLUSIONS: These results highlight the need for planning specific supports for minors with ASD and for resources to reverse the effects on routines, habits, and school returnal.

TITLE: Análisis del impacto de la COVID-19 en menores de edad con trastorno del espectro autista.Introducción. La declaración del confinamiento domiciliario a raíz de la pandemia de la COVID-19 alteró profundamente las rutinas y el acceso a soportes sociosanitarios en menores de edad con trastorno del espectro autista (TEA). Esta población se distingue por su elevada complejidad de manejo y vulnerabilidad ante cambios. Objetivos. Evaluar cualitativamente el estado psicosocial en menores con TEA atendidos en el Hospital Clínic de Barcelona durante el confinamiento y pasado éste. Pacientes y métodos. Se administró una encuesta, elaborada específicamente para este estudio, a los cuidadores principales de 65 niños y niñas con diagnóstico principal de TEA. Resultados. Se observó una regresión en la sintomatología nuclear del TEA. Además, aumentó el uso de nuevas tecnologías y la ingesta entre comidas, y apareció una sintomatología ansiosa. La recuperación tras el confinamiento no fue total en nuestra muestra. Conclusiones. Los resultados ponen de relieve la necesidad de planificación de soportes específicos para los menores con TEA y de recursos para revertir las afectaciones en las rutinas, los hábitos y la incorporación escolar.

Development of Bioactive Glass-Collagen-Hyaluronic Acid-Polycaprolactone Scaffolds for Tissue Engineering Applications.

In this work, bioactive glass (BG) particles synthesized by a sol-gel method, hyaluronic acid (HYA) and collagen (COL) extracted from chicken eggshell membrane (ESM), and as-purchased polycaprolactone (PCL) were used to obtain a novel bioactive scaffold using the gel-pressing technique. Two composite mixtures in weight percent were obtained and identified as SCF-1 and SCF-2, and were characterized by using FTIR, XRD, and SEM techniques. Subsequently, the composite materials applied as coatings were evaluated in simulated body fluid solutions using electrochemical techniques. The results of bioactivity and biodegradability evaluations, carried out by immersing in simulated body fluid and phosphate-buffered saline solution, showed that the SCF-1 sample presented the best biocompatibility. In accordance with the potentiodynamic results, the 316L-SS and the SCF-1-coated SS showed a very similar corrosion potential (E corr ), around -228 mV, and current density (i corr ) values in close proximity, while the SCF-2-coated SS showed more positive E corr around -68 mV and lower i corr value in one order of magnitude. These results agree with those obtained by electrochemical impedance spectroscopy, which show a corrosion mechanism governed by activation and finite diffusion through the porous layer. In addition, results were complemented by dynamic compression testing under oscillating forces to identify the developed scaffolds' response under external forces, where the SCF-1 scaffold presented a maximum compression. The degradation resistance, bioactivity, and mechanically obtained measurements provided interesting results for potential further studies in tissue engineering.

A real-life overview of a hematopoietic cell transplant program throughout a four-year period, including prospective registry, exclusion causes and final donor selection.

Traceability of patients who are candidates for Hematopoietic cell transplant (HCT) is crucial to ensure HCT program quality. Continuous knowledge of both a detailed registry from a HCT program and final exclusion causes can contribute to promoting a real-life vision and optimizing patient and donor selection. We analyzed epidemiological data reported in a 4 year-monocentric prospective registry, which included all patients presented as candidates for autologous (Auto) and/or allogeneic (Allo) HCT. A total of 543 patients were considered for HCT: 252 (42.4%) for Allo and 291 (57.6%) for Auto. A total of 98 (38.9%) patients were excluded from AlloHCT due to basal disease progression more commonly (18.2%). Seventy-six (30.2%) patients had an HLA identical sibling, whereas 147 (58.3%) patients had only Haplo. UD research was performed in 106 (42%) cases, significantly more often in myeloid than lymphoid malignancies (57% vs 28.7%, p < 0.001) but 61.3% were finally canceled, due to donor or disease causes in 72.4%. With respect to Auto candidates, a total of 60 (20.6%) patients were finally excluded; progression was the most common cause (12%). Currently, Haplo is the most frequent donor type. The high cancellation rate of UD research should be revised to optimize further donor algorithms.

Oxidative cleavage of C-C bonds in lignin.

Lignin is an aromatic polymer that constitutes up to 30 wt% of woody biomass and is considered the largest source of renewable aromatics. Valorization of the lignin stream is pivotal for making biorefining sustainable. Monomeric units in lignin are bound via C-O and C-C bonds. The majority of existing methods for the production of valuable compounds from lignin are based on the depolymerization of lignin via cleavage of relatively labile C-O bonds within lignin structure, which leads to yields of only 36-40 wt%. The remaining fraction (60 wt%) is a complex mixture of high-molecular-weight lignin, generally left unvalorized. Here we present a method to produce additional valuable monomers from the high-molecular-weight lignin fraction through oxidative C-C bond cleavage. This oxidation reaction proceeds with a high selectivity to give 2,6-dimethoxybenzoquinone (DMBQ) from high-molecular-weight lignin in 18 wt% yield, thus increasing the yield of monomers by 32%. This is an important step to make biorefining competitive with petroleum-based refineries.

PCSK9 Gene Participates in the Development of Primary Dyslipidemias.

Dyslipidemias are a group of diseases, which are characterized by abnormal blood concentrations of cholesterol, triglycerides and/or low-density lipoprotein-cholesterol (LDL-c). Dyslipidemia is a determinant condition for the progress of an atherosclerotic plaque formation. The resulting atherogenicity is due to at least two mechanisms: first, to the accumulation in the plasma of lipid particles that have the capacity to alter the function of the endothelium and deposit at the atheromatous plaque, and second, at an insufficient concentration of multifactorial type of high density lipoprotein-cholesterol (HDL-c), whose function is to protect against the development of atherosclerosis. Its highest prevalence is encountered among individuals with diabetes, hypertension or overweight. Hyperlipidemia is one of the main predisposing factors for the development of cardiovascular disease. Hyperlipidemia can be the result of a genetic condition, the secondary expression of a primary process or the consequence of exogenous factors (food, cultural, socio-economic, etc.), all of which lead to the elevation of plasma lipid levels. The objective of this study was to carry out an analysis of the genes involved in the development of dyslipidemias that lead to cardiovascular disease with special emphasis on the proprotein convertase subtilin/kexin type 9 (PCSK9) gene. The PCSK9 gene participates in the development of primary dyslipidemias, mainly familial hypercholesterolemia, currently the pharmacological treatment of choice to reduce LDL-c are statins, however, it has been observed that these have been insufficient to eliminate cardiovascular risk, especially in subjects with primary forms of hypercholesterolemia related to genetic mutations, or statin intolerance.

Mussismilia braziliensis White Plague Disease Is Characterized by an Affected Coral Immune System and Dysbiosis.

Infectious diseases are one of the major drivers of coral reef decline worldwide. White plague-like disease (WPL) is a widespread disease with a complex etiology that infects several coral species, including the Brazilian endemic species Mussismilia braziliensis. Gene expression profiles of healthy and WPL-affected M. braziliensis were analyzed in winter and summer seasons. The de novo assembly of the M. braziliensis transcriptome from healthy and white plague samples produced a reference transcriptome containing 119,088 transcripts. WPL-diseased samples were characterized by repression of immune system and cellular defense processes. Autophagy and cellular adhesion transcripts were also repressed in WPL samples, suggesting exhaustion of the coral host defenses. Seasonal variation leads to plasticity in transcription with upregulation of intracellular signal transduction, apoptosis regulation, and oocyte development in the summer. Analysis of the active bacterial rRNA indicated that Pantoea bacteria were more abundant in WPL corals, while Tistlia, Fulvivirga, and Gammaproteobacteria Ga0077536 were more abundant in healthy samples. Cyanobacteria proliferation was also observed in WPL, mostly in the winter. These results indicate a scenario of dysbiosis in WPL-affected M. braziliensis, with the loss of potentially symbiotic bacteria and proliferation of opportunistic microbes after the start of the infection process.

Xeno-free approach for the expansion of human adipose derived mesenchymal stem cells for ocular therapies.

To restore corneal transparency and vision loss after an injury on the ocular surface, the use of human stem cells from different origins has been recently proposed. Mesenchymal stem cells (MSCs) seem to be an appropriate adult source of autologous stem cells due to their accessibility, high proliferation rate, and multipotent capacity. In this work, we developed a simple culture system to prepare a graft based on a fibrin membrane seeded with human MSCs. A commercial kit, PRGF Endoret®, was used to prepare both, the growth factors used as culture media supplement and the fibrin membrane grafts. Adipose-derived MSCs (Ad-MSCs) were expanded, characterised by flow cytometry and their multilineage differentiation potential confirmed by inducing adipogenesis, osteogenesis and chondrogenesis. Ad-MSCs seeded on the fibrin membranes were grafted onto athymic mice showing good biocompatibility with no adverse reactions observed during the follow up period. These findings support the assumption that a system in which all the biological components (cells, grow factors and carrier) are autologous, could potentially be used for future ex vivo expansion of Ad-MSCs to treat ocular conditions such as an inflammatory milieu, traumatic scars and loss of the regenerative capacity of the corneal epithelium that compromise the quality of vision.