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ABSTRACT A substantial number of patients undergoing coronary angiography for angina or ischemia in noninvasive tests have coronary arteries without lesions or with nonsignificant stenosis. Many of these patients have nonobstructive myocardial ischemia (INOCA/ANOCA), which is an entity with prognostic importance that significantly affects patients’ quality of life. The absence of a proper diagnosis leads to inappropriate medical treatment, repeat diagnostic tests, and greater use of social and health resources. An adequate diagnostic strategy is required for individualized treatment that improves symptoms and quality of life. In this document from the SEC-Clinical Cardiology Association, SEC Interventional Cardiology Association, SEC-Ischemic Heart Disease and Acute Cardiac Care Association, and SEC-Cardiovascular Imaging Association of the Spanish Society of Cardiology, we provide simple and practical algorithms, with the aim of facilitating the early diagnosis and most appropriate treatment for patients with ANOCA. Keywords: ANOCA. INOCA. Microvascular dysfunction. Vasospastic angina. RESUMEN Un número importante de aquellos pacientes en quienes se realiza coronariografía por angina o isquemia presentan en pruebas no invasivas arterias coronarias sin lesiones o con estenosis no significativas. Muchos de estos pacientes tienen isquemia miocárdica de causa no obstructiva (INOCA/ANOCA), una condición con importancia pronóstica que afecta de manera considerable la calidad de vida. La ausencia de un diagnóstico que haga...

RESUMEN Un número importante de aquellos pacientes en quienes se realiza coronariografía por angina o isquemia presentan en pruebas no invasivas arterias coronarias sin lesiones o con estenosis no significativas. Muchos de estos pacientes tienen isquemia miocárdica de causa no obstructiva (INOCA/ANOCA), una condición con importancia pronóstica que afecta de manera considerable la calidad de vida. La ausencia de un diagnóstico que haga posible un tratamiento médico efectivo acarrea la repetición de pruebas diagnósticas y un mayor uso de recursos sociosanitarios. Es necesaria una estrategia diagnóstica adecuada para poder realizar un tratamiento personalizado, que mejore los síntomas y la calidad de vida. En este documento de la SEC-Asociación de Cardiología Clínica, SEC-Asociación de Cardiología Intervencionista, SEC-Asociación de Cardiopatía Isquémica y Cuidados Agudos Cardiovasculares, y SEC-Asociación de Imagen Cardiaca, se establecen unos algoritmos sencillos y prácticos con el objetivo de facilitar el diagnóstico precoz y el tratamiento más adecuado de los pacientes con ANOCA. Palabras clave: ANOCA. INOCA. Disfunción microvascular. Angina vasoespástica. ABSTRACT A substantial number of patients undergoing coronary angiography for angina or ischemia in noninvasive tests have coronary arteries without lesions or with nonsignificant stenosis. Many of these patients have nonobstructive myocardial ischemia (INOCA/ANOCA), which is an entity with prognostic importance that significantly affects patients’ quality of...

It is customary to classify approaches in statistical mechanics (SM) as belonging either to Boltzmanninan SM (BSM) or Gibbsian SM (GSM). It is, however, unclear how the Boltzmann equation (BE) fits into either of these approaches. To discuss the relation between BE and BSM, we first present a version of BSM that differs from standard presentation in that it uses local field variables to individuate macro-states, and we then show that BE is a special case of BSM thus understood. To discuss the relation between BE and GSM, we focus on the BBGKY hierarchy and note the version of the BE that follows from the hierarchy is “Gibbsian” only in the minimal sense that it operates with an invariant measure on the state space of the full system.

El presente artículo, presenta un panorama general de las metodologías más usadas en la enseñanza del derecho, tales como la cátedra magistral y la casuística o estudio de casos. Se presentará una revisión de estas dos metodologías, señalando sus beneficios y también sus debilidades. Se finalizará con una propuesta de metodología didáctica para la enseñanza del derecho, que proviene de los Moot Court explicando en que consiste, como puede ser aplicado en las asignaturas teóricas y prácticas, así como sus ventajas y debilidades. Para esta última parte se contará con las visiones de diferentes profesores, que no solo participaron como estudiantes sino también como tutores, jueces y creadores de estos concursos. Se hará énfasis en los Moot Court que se realizan en Colombia, como expresión de la innovación metodológica de algunos centros de educación Superior como la Universidad Militar Nueva Granada y la Universidad Libre de Cartagena.

Abstract Background Surrogate production by germline stem cell transplantation is a powerful method to produce donor-derived gametes via a host, a practice known as surrogacy. The gametes produced by surrogates are often analysed on the basis of their morphology and species-specific genotyping, which enables conclusion to be drawn about the donor’s characteristics. However, in-depth information, such as data on epigenetic changes, is rarely acquired. Germ cells develop in close contact with supporting somatic cells during gametogenesis in vertebrates, and we hypothesize that the recipient’s gonadal environment may cause epigenetic changes in produced gametes and progeny. Here, we extensively characterize the DNA methylome of donor-derived sperm and their intergenerational effects in both inter- and intraspecific surrogates. Results We found more than 3000 differentially methylated regions in both the sperm and progeny derived from inter- and intraspecific surrogates. Hypermethylation in the promoter regions of the protocadherin gamma gene in the intraspecific surrogates was found to be associated with germline transmission. On the contrary, gene expression level and the embryonic development of the offspring remained unaffected. We also discovered MAPK/p53 pathway disruption in interspecific surrogates due to promoter hypermethylation and identified that the inefficient removal of meiotic-arrested endogenous germ cells in hybrid gonads led to the production of infertile spermatozoa. Conclusions Donor-derived sperm and progeny from inter- and intraspecific surrogates were more globally hypermethylated than those of the donors. The observed changes in DNA methylation marks in the surrogates had no significant phenotypic effects in the offspring.

Abstract Coordination of a stereochemically defined P3‐chain to a series of transition metal carbonyls [M(CO)x]z− (M = Mn (x = 5, z = 1), Fe (x = 4, z = 2) or Co (x = 4, z = 1)) is explored using a [3]ferrocenophane scaffold. A gradual transition from η1‐, η2‐ to η3‐coordination is observed where in the η2‐mode the terminal positions of the phosphorus chain are bridged. With an excess of cobalt carbonyl successive P–P bond activation and gradual separation of the central phosphorus atoms from the phosphorus chain has been observed. This process is reversible and with suitable reagents such as methyl lithium, the P3‐unit is regenerated in stereospecific manner. The bonding situation and steps of the gradual P–P bond activation are investigated by DFT calculations as well as experimental methods (e.g., NMR spectroscopy, X‐ray crystallography).

In this work, three wheat crops were planted successively under semi-arid climatic conditions; we wished to evaluate the positive and negative effects of the addition of sewage sludge (SS) on plants and soils under the conditions encountered during conventional agricultural management. SS was added to the first two crops at doses equivalent to 170 kg N/ha, and the third crop was left untreated. The soils were sampled initially and at the end of each cultivation period. At the end of the third crop’s cultivation period, the heavy metal and organic pollutant contents of grain and straw were analyzed, as well as the presence of Escherichia coli and Salmonella. The amended soils showed a higher N content, greater microbial respiration, and greater dehydrogenase and phosphatase activity than the control. The amended plants showed higher N, Ca, and K contents than the control. Yields were 11% and 16% higher in the SS-amended soils than in the control in the experiments involving the second and third crop, respectively. No problems related to salinity or the heavy metal content were observed in both the soil and plant. However, nitrate content increased in the amended soils compared to the control. Among the persistent organic compounds, only linear alkyl benzene sulphonates and polycyclic aromatic hydrocarbons increased with the addition of SS, but such differences from the control disappeared gradually. No problematic coliform content or presence of Salmonella spp. was detected in the soil or plant. We can thus conclude that SS of adequate quality can be recycled in agricultural soils, but adequate monitoring of the receiving soil is crucial.

Educación indígena en Colombia

Abstract Zebrafish (Danio rerio) is a commonly-used vertebrate model species for many research areas. However, its low milt volume limits effective cryopreservation of sperm from a single individual and often precludes dividing a single semen sample to conduct multiple downstream procedures such as genomic DNA/RNA extraction and in-vitro fertilization. Here, we apply germ stem cell transplantation to increase zebrafish sperm production in a closely related larger species from the same subfamily, giant danio Devario aequipinnatus. The endogenous germ cell of the host is depleted by dead-end morpholino antisense oligonucleotide. Histology of the sterile gonad and quantitative PCR of gonadal tissue reveals all sterile giant danio develop the male phenotype. Spermatogonial cells of Tg(ddx4:egfp) transgenic zebrafish are transplanted into sterile giant danio larvae, and 22% of recipients (germline chimera) produce donor-derived sperm at sexual maturation. The germline chimera produce approximately three-fold the volume of sperm and 10-fold the spermatozoon concentration of the donor. The donor-derived sperm is functional and gives rise to viable progeny upon fertilization of donor oocytes. We show that the issue of low milt volume can be effectively addressed by employing a larger surrogate parent.

Abstract Background The non-neuronal retinal pigment epithelium (RPE) functions in intimate association with retinal photoreceptors, performing a multitude of tasks critical for maintaining retinal homeostasis and collaborating with retinal glial cells to provide metabolic support and ionic buffering. Accordingly, the RPE has recently been shown to display dynamic properties mediated by an array of ion channels usually more characteristic of astrocytes and excitable cells. The recent discovery of canonical voltage-activated Na+ channels in the RPE and their importance for phagocytosis of photoreceptor outer segments raises a question about their electrogenic function. Here, we performed a detailed electrophysiological analysis related to the functioning of these channels in human embryonic stem cell (hESC)-derived RPE. Results Our studies examining the electrical properties of the hESC-RPE revealed that its membrane mainly displays passive properties in a broad voltage range, with the exception of depolarization-induced spikes caused by voltage-activated Na+ current (I Na). Spike amplitude depended on the availability of I Na and spike kinetics on the membrane time constant, and the spikes could be largely suppressed by TTX. Membrane resistance fluctuated rapidly and strongly, repeatedly changing over the course of recordings and causing closely correlated fluctuations in resting membrane potential. In a minority of cells, we found delayed secondary I Na-like inward currents characterized by comparatively small amplitudes and slow kinetics, which produced secondary depolarizing spikes. Up to three consecutive delayed inward current waves were detected. These currents could be rapidly and reversibly augmented by applying L-type Ca2+ channel blocker nifedipine to diminish influx of calcium and thus increase gap junctional conductance. Conclusions This work shows, for the first time, that I Na and I Na-mediated voltage spikes can spread laterally through gap junctions in the monolayer of cells that are traditionally considered non-excitable. Our findings support a potential role of the RPE that goes beyond giving homeostatic support to the retina.

Pituitary hormones play a central role in shaping vertebrate life history events, including growth, reproduction, metabolism, and aging. The regulation of these traits often requires precise control of hormone levels across diverse timescales. However, fine tuning circulating hormones in-vivo has traditionally been experimentally challenging. Here, using the naturally short-lived turquoise killifish (N. furzeri), we describe a high-throughput platform that combines loss- and gain-of-function of peptide hormones. Mutation of three primary pituitary hormones, growth hormone (gh1), follicle stimulating hormone (fshb), and thyroid stimulating hormone (tshb), alters somatic growth and reproduction. Thus, suggesting that while the killifish undergoes extremely rapid growth and maturity, it still relies on vertebrate-conserved genetic networks. As the next stage, we developed a gain-of-function vector system in which a hormone is tagged using a self-cleavable fluorescent reporter, and ectopically expressed in-vivo through intramuscular electroporation. Following a single electroporation, phenotypes, such as reproduction, are stably rescued for several months. Notably, we demonstrate the versatility of this approach by using multiplexing, dose-dependent, and doxycycline-inducible systems to achieve tunable and reversible expression. In summary, this method is relatively high-throughput, and facilitates large-scale interrogation of life-history strategies in fish. Ultimately, this approach could be adapted for modifying aquaculture species and exploring pro-longevity interventions.

Aim: It is not well known how comorbidities may change the prognosis of atrial fibrillation (AF) patients. This study was aimed to analyze the impact of cardiovascular disease on this population. Materials & methods: EMIR was a multicenter, prospective study, including 1433 AF patients taking rivaroxaban for ≥6 months. Data were analyzed according to the presence of vascular disease. Results: Coronary artery disease was detected in 16.4%, peripheral artery disease/aortic plaque in 6.7%, vascular disease in 28.3%. Patients with coronary artery disease had higher rates (per 100 patient-years) of major adverse cardiovascular events (2.98 vs 0.71; p < 0.001) and cardiovascular death (1.79 vs 0.41; p = 0.004). Those with vascular disease had higher rates of thromboembolic events (1.47 vs 0.44; p = 0.007), major adverse cardiovascular events (2.03 vs 0.70; p = 0.004), and cardiovascular death (1.24 vs 0.39; p = 0.025). Patients with peripheral artery disease/aortic plaque had similar rates. Conclusion: AF patients with vascular disease have a higher risk of non-embolic outcomes.

Common carp (Cyprinus carpio) is the fourth most-produced fish species in aquaculture and frequently used model species with significant effort invested in development of biotechnological applications. In present study, we attempted to establish an in vitro germ cell culture condition for short term cell culture, which could facilitate further applications such as surrogacy or gene manipulation. Basal media and different types of feeder cells were investigated to optimize carp germ cell culture condition to favor maintenance of mitotic proliferation. Results indicated that germ cells cultured with hESC media and RTG2 cell line as feeder possessed significantly higher proliferation and survival rate compared to that cultured with StemPro media and Sertoli cell line as feeder. In addition, we compared two dissection strategies to compare risk of cell culture contamination and body cavity was open from dorsal part or from ventral part. As a result, carp open from the dorsal side can minimize the risk of contamination. In summary, this is the first study to optimize the cultivation of germ cells in common carp. This opens up new opportunities for the application of specific techniques in the breeding of those species with high commercial value and frequent use as a model fish. Results obtained in this study are important for implementation of new strategies in common carp breeding, conservation of genetic resources, restoration of lines or development of clonal and isogenic carp lines.

Medical complications during pregnancy have been frequently reported from Western Africa with a particular importance of infectious complications. Placental tissue can either become the target of infectious agents itself, such as, e.g., in the case of urogenital schistosomiasis, or be subjected to contamination with colonizing or infection-associated microorganisms of the cervix or the vagina during vaginal delivery. In the retrospective cross-sectional assessment presented here, the quantitative dimension of infection or colonization with selected resistant or pathogenic bacteria and parasites was regionally assessed. To do so, 274 collected placental tissues from Ivory Coastal and Ghanaian women were subjected to selective growth of resistant bacteria, as well as to molecular screening for beta-lactamase genes, Schistosoma spp. and selected bacterial causative agents of sexually transmitted infections (STI). Panton–Valentine-negative methicillin-resistant Staphylococcus aureus (MRSA) was grown from 1.8% of the tissue samples, comprising the spa types t008 and t688, as well as the newly detected ones, t12101 (n = 2) and t12102. While the culture-based recovery of resistant Enterobacterales and nonfermentative rod-shaped Gram-negative bacteria failed, molecular assessments confirmed beta-lactamase genes in 31.0% of the samples with multiple detections of up to four resistance genes per sample and blaCTX-M, blaIMP, blaGES, blaVIM, blaOXA-58-like, blaNDM, blaOXA-23-like, blaOXA-48-like and blaKPC occurring in descending order of frequency. The beta-lactamase genes blaOXA-40/24-like, blaNMC_A/IMI, blaBIC, blaSME, blaGIM and blaDIM were not detected. DNA of the urogenital schistosomiasis-associated Schistosoma haematobium complex was recorded in 18.6% of the samples, but only a single positive signal for S. mansoni with a high cycle-threshold value in real-time PCR was found. Of note, higher rates of schistosomiasis were observed in Ghana (54.9% vs. 10.3% in Ivory Coast) and Cesarean section was much more frequent in schistosomiasis patients (61.9% vs. 14.8% in women without Schistosoma spp. DNA in the placenta). Nucleic acid sequences of nonlymphogranuloma-venereum-associated Chlamydia trachomatis and of Neisseria gonorrhoeae were recorded in 1.1% and 1.9% of the samples, respectively, while molecular attempts to diagnose Treponema pallidum and Mycoplasma genitalium did not lead to positive results. Molecular detection of Schistosoma spp. or STI-associated pathogens was only exceptionally associated with multiple resistance gene detections in the same sample, suggesting epidemiological distinctness. In conclusion, the assessment confirmed considerable prevalence of urogenital schistosomiasis and resistant bacterial colonization, as well as a regionally expected abundance of STI-associated pathogens. Continuous screening offers seem advisable to minimize the risks for the pregnant women and their newborns.

This manuscript presents an efficient algorithm for solving the inverse kinematics problem of a 6R robot manipulator to be deployed on embedded control hardware. The proposed method utilizes the geometric relationship between the end-effector and the base of the manipulator, resulting in a computationally efficient solution. The approach aims to minimize computational complexity and memory consumption while maintaining the accuracy and real-time performance demonstrated by simulations and verified by experimental results on an embedded system. Furthermore, the manipulator is analyzed in terms of singularities, limits, the workspace, and general solvability. Due to the simplicity of the algorithm, a platform-independent implementation is possible. As a result, the average calculation time is reduced by a factor of five to eight and the average error is decreased by a factor of fifty compared to a powerful analytical solver.

Abstract Aims The role of non‐invasive telemedicine (TM) combining telemonitoring and teleintervention by videoconference (VC) in patients recently admitted due to heart failure (HF) (‘vulnerable phase’ HF patients) is not well established. The aim of the Heart failure Events reduction with Remote Monitoring and eHealth Support (HERMeS) trial is to assess the impact on clinical outcomes of implementing a TM service based on mobile health (mHealth), which includes remote daily monitoring of biometric data and symptom reporting (telemonitoring) combined with VC structured, nurse‐based follow‐up (teleintervention). The results will be compared with those of the comprehensive HF usual care (UC) strategy based on face‐to‐face on‐site visits at the vulnerable post‐discharge phase. Methods and results We designed a 24 week nationwide, multicentre, randomized, controlled, open‐label, blinded endpoint adjudication trial to assess the effect on cardiovascular (CV) mortality and non‐fatal HF events of a TM‐based comprehensive management programme, based on mHealth, for patients with chronic HF. Approximately 508 patients with a recent hospital admission due to HF decompensation will be randomized (1:1) to either structured follow‐up based on face‐to‐face appointments (UC group) or the delivery of health care using TM. The primary outcome will be a composite of death from CV causes or non‐fatal HF events (first and recurrent) at the end of a 6 month follow‐up period. Key secondary endpoints will include components of the primary event analysis, recurrent event analysis, and patient‐reported outcomes. Conclusions The HERMeS trial will assess the efficacy of a TM‐based follow‐up strategy for real‐world ‘vulnerable phase’ HF patients combining telemonitoring and teleintervention.

In the last decade, the CRISPR/Cas9 bacterial virus defense system has been adapted as a user-friendly, efficient, and precise method for targeted mutagenesis in eukaryotes. Though CRISPR/Cas9 has proven effective in a diverse range of organisms, it is still most often used to create mutant lines in lab-reared genetic model systems. However, one major advantage of CRISPR/Cas9 mutagenesis over previous gene targeting approaches is that its high efficiency allows the immediate generation of near-null mosaic mutants. This feature could potentially allow genotype to be linked to phenotype in organisms with life histories that preclude the establishment of purebred genetic lines; a group that includes the vast majority of vertebrate species. Of particular interest to scholars of early vertebrate evolution are several long-lived and slow-maturing fishes that diverged from two dominant modern lineages, teleosts and tetrapods, in the Ordovician, or before. These early-diverging or “basal” vertebrates include the jawless cyclostomes, cartilaginous fishes, and various non-teleost ray-finned fishes. In addition to occupying critical phylogenetic positions, these groups possess combinations of derived and ancestral features not seen in conventional model vertebrates, and thus provide an opportunity for understanding the genetic bases of such traits. Here we report successful use of CRISPR/Cas9 mutagenesis in one such non-teleost fish, sterlet Acipenser ruthenus, a small species of sturgeon. We introduced mutations into the genes Tyrosinase, which is needed for melanin production, and Sonic hedgehog, a pleiotropic developmental regulator with diverse roles in early embryonic patterning and organogenesis. We observed disruption of both loci and the production of consistent phenotypes, including both near-null mutants’ various hypomorphs. Based on these results, and previous work in lamprey and amphibians, we discuss how CRISPR/Cas9 F0 mutagenesis may be successfully adapted to other long-lived, slow-maturing aquatic vertebrates and identify the ease of obtaining and injecting eggs and/or zygotes as the main challenges.

Sturgeons are among the most ancient linages of actinopterygians. At present, many sturgeon species are critically endangered. Surrogate production could be used as an affordable and a time-efficient method for endangered sturgeons. Our study established a method for identifying and isolating type A spermatogonia from different developmental stages of testes using flow cytometric cell sorting (FCM). Flow cytometric analysis of a whole testicular cell suspension showed several well-distinguished cell populations formed according to different values of light scatter parameters. FCM of these different cell populations was performed directly on glass slides for further immunocytochemistry to identify germ cells. Results showed that the cell population in gate P1 on a flow cytometry plot (with high forward scatter and high side scatter parameter values) contains the highest amount of type A spermatogonia. The sorted cell populations were characterized by expression profiles of 10 germ cell specific genes. The result confirmed that setting up for the P1 gate could precisely sort type A spermatogonia in all tested testicular developmental stages. The P2 gate, which was with lower forward scatter and side scatter values mostly, contained type B spermatogonia at a later maturing stage. Moreover, expressions of plzf, dnd, boule, and kitr were significantly higher in type A spermatogonia than in later developed germ cells. In addition, plzf was firstly found as a reliable marker to identify type A spermatogonia, which filled the gap of identification of spermatogonial stem cells in sterlet. It is expected to increase the efficiency of germ stem cell culture and transplantation with plzf identification. Our study thus first addressed a phenotypic characterization of a pure type A spermatogonia population in sterlet. FCM strategy can improve the production of sturgeons with surrogate broodstock and further the analysis of the cellular and molecular mechanisms of sturgeon germ cell development.

Abstract Background Central drop foot is a common problem in patients with stroke or multiple sclerosis (MS). For decades, it has been treated with orthotic devices, keeping the ankle in a fixed position. It has been shown recently that semi-implantable functional electrical stimulation (siFES) of the peroneal nerve can lead to a greater gait velocity increase than orthotic devices immediately after being switched on. Little is known, however, about long-term outcomes over 12 months, and the relationship between quality of life (QoL) and gait speed using siFES has never been reported applying a validated tool. We provide here a report of short (3 months) and long-term (12 months) outcomes for gait speed and QoL. Methods Forty-five consecutive patients (91% chronic stroke, 9% MS) with central drop foot received siFES (Actigait®). A 10 m walking test was carried out on day 1 of stimulation (T1), in stimulation ON and OFF conditions, and repeated after 3 (T2) and 12 (T3) months. A 36-item Short Form questionnaire was applied at all three time points. Results We found a main effect of stimulation on both maximum (p

This paper highlights a need to make a transition from a compulsory military service to voluntary-and-professional enlistment in line with the new way of state established by Constitution in 1991, whose cornerstone is the constitutional value and principle as a function of basic right of dignity of the human being. Faced with this view there are some countries having done this transition, evidencing that modern states don’t require the compulsory military service since its abolition is not a detriment to security; otherwise, a professionalization of this job could result in a more effective defense and security. This paper also addresses a formula that could solve the defense and security issues of the Colombian state thanks to active military reserve members that, in the event of war, would supply the lack of youth forced. Finally, an analysis of the Constitutional Court rulings against the enforceability of this standard as well as ending this obligation from a conscientious objection and a legislature absence to rule this voluntarism despite the recommendation by the Constitutional Court.

La sumisión de las fuerzas militares no está defnida plenamente en el presidente de la República como su Comandante Supremo, y quien funge como máxima autoridad administrativa y representante de la unidad de la nación. Por otra parte, es evidente que el pueblo no posee la capacidad real de exigir el sometimiento de las Fuerzas Militares mediante las acciones que le otorga la Constitución Política (en adelante CN), aun cuando este es su creador y, por ende, su mandante. En este artículo se plantean aspectos relacionados con la fuga del poder de la soberanía del pueblo hacia sus mandatarios, para este efecto se utilizó el método histórico lógico. En todo el recorrido de acontecimientos que se hace, se percibe cómo el pueblo cedió gradualmente su poder en cabeza de sus representantes, quienes, en posesión de él, paulatinamente lo utilizaron para su benefcio personal o de sus partidos y movimientos en detrimento del pueblo

The aim of the present study was to investigate the spontaneous motility of spermatozoa and to optimize sperm collection, short-term sperm storage, and fertilization in zebrafish Danio rerio. The movement of spermatozoon in water was propagated along the flagellum at 16 s after sperm activation then damped from the end of the flagellum for 35 s and fully disappeared at 61 s after activation. For artificial fertilization, milt must be added to an immobilizing solution, which stops the movement of sperm and keeps the sperm motionless until fertilization. E400 and Kurokura as isotonic solutions were shown to be suitable extenders to store sperm for fertilization for 6 h. E400 stored sperm for 12 h at 0–2 °C. Sperm motility decreased only to 36% at 12 h post stripping for the E400 extender and to 19% for the Kurokura extender. To achieve an optimal level of fertilization and swim-up larvae rates, a test tube with a well-defined amount of 6,000,000 spermatozoa in E400 extender per 100 eggs and 100 µL of activation solution has proven to be more successful than using a Petri dish. The highest fertilization and swim-up larvae rates reached 80% and 40–60%, respectively, with milt stored for 1.5 h in the E400 extender at 0–2 °C.

Fish egg quality can be markedly influenced by the oocyte age after ovulation. In this study, we examined the duration of oocyte ageing in the zebrafish (Danio rerio) and whether prolonged ageing is associated with the incidence of ploidy anomalies in the resulting embryos. Oocytes were incubated in vitro for 6 h post-stripping (HPS) at 26 °C and fertilized at 2-h intervals. Meanwhile, for eggs fertilized immediately after stripping, the fertilization, embryo survival, and hatching rates started at ~80%; these rates decreased to 39%, 24%, and 16%, respectively, for oocytes that had been stored for 4 h (p ˂ 0.05), and there was an almost complete loss of egg viability at 6 HPS. Furthermore, almost 90% of the embryos derived from 6-h aged oocytes died prior to hatching, and all larvae originating from 4- and 6-h aged oocytes showed malformations. The proportion of ploidy abnormal embryos was significantly greater at 4 HPS (18.5%) than at either 0 or 2 HPS (4.7% and 8.8%, respectively). The results revealed that zebrafish oocytes retained their fertilization potential for up to 2 h after stripping at 26 °C and indicated the contribution of post-ovulatory oocyte ageing in the occurrence of ploidy anomalies in the resulting embryos.

tert-Butyl-substituted diphospha[2]ferrocenophane was used as a stereochemically confined diphosphane to investigate the addition of various dichalcoganes (R2Ch2; Ch = S, Se, Te and R = Me, Ph). Bischalcogenophosphinous acid esters bearing four soft donor sides were obtained as a mixture of rac and meso diastereomers and characterized by means of multinuclear NMR and X-ray analysis. The coordination chemistry of multidentate ligand 3b was explored toward d10 coinage metal centers (Cu(I), Ag(I), and Au(I)), yielding various bimetallic complexes.

The analysis aimed at studying stresses reduced according to Huber’s hypothesis and displacement patterns at selected sites of the facial skeleton using a tooth-borne appliance in surgically assisted rapid maxillary expansion. Five different variants of osteotomy of the midface and a variant without surgical intervention were compared to determine the best model for making an incision in the maxilla. The finite element analysis (FEA) was used for the study. Five osteotomy variants and a variant without osteotomy were modelled using a tooth-borne appliance on a facial skeleton model of a 23-year-old woman with skeletal malocclusion. The finite element mesh was constructed based on the geometry imported into the ANSYS 15.0 (Swanson Analysis System of USA) software, in which calculations were performed using the finite element analysis. Stress distributions and displacement patterns along the X, Y and Z axes are presented for each osteotomy variant with the expansion of the tooth-borne appliance at a level of 0.5 mm. As a result of the analysis it was found that osteotomy of the palatal suture in conjunction with Le Fort I osteotomy has the biggest impact on the course of maxillary expansion. If no osteotomy is performed, an increase in stresses reduced according to Huber occurs in the entire facial skeleton with a simultaneous absence of maxillary expansion.

Common carp (Cyprinus carpio) is one of the most cultured fish species over the world with many different breeds and plenty of published protocols for sperm cryopreservation. However, data regarding preservation of gonadal tissue and surrogate production is still missing. A protocol for freezing common carp spermatogonia was developed through varying different factors along a set of serial subsequent experiments. Among the six cryoprotectants tested, the best survival was achieved with dimethyl sulfoxide (Me2SO). In the next experiment, a wide range of cooling rates (0.5-10°C/min) and different concentrations of Me2SO were tested resulting in the highest survival achieved using 2 M Me2SO and cooling rate of -1°C/min. When testing different tissue sizes and incubation times in the cryomedia, the highest viability was observed when incubating 100 mg tissue fragments for 30 min. Finally, sugar supplementation did not yield significant differences. When testing different equilibration (ES) and vitrification solutions (VS) used for needle-immersed vitrification, no significant differences were observed between the tested groups. Additionally, varied exposure time to VS did not improve the vitrification outcome where the viability was 4-fold lower than that of freezing. The functionality of cryopreserved cells was tested by interspecific transplantation into sterilized goldfish recipients. The exogenous origin of the germ cells in gonads of goldfish recipient was confirmed by molecular markers and incorporation rate was over 40% at 3 months post-transplantation. Results of this study can serve for long-term preservation of germplasm in carp which can be recovered in a surrogate recipient.

Después de la independencia, la organización administrativa del Estado colombiano hacia un modelo de corte liberal y capitalista fue inmediata. No obstante, por parte de quienes se resis - tían a perder antiguas prerrogativas, surgieron prácticas conducentes a beneficiar los intereses particulares, aun cuando dicho beneficio debiera tocar los sagrados bienes públicos. El objetivo del artículo es ilustrar acerca de una de las mayores vulneraciones que sufrió Colombia en los primeros años de vida republicana: la corrupción, entendida desde el siguiente interrogante: ¿es posible afirmar que el Estado colombiano, concebido y desarrollado a partir de la independencia de 1819 y gestado con principios administrativos modernos, se mantuvo al margen de acciones y prácticas contrarias a la eticidad y buen manejo que la función pública exige? Responder a tal pregunta requirió de un ejercicio histórico, en el cual predominó el análisis histórico-lógico, como la vía más conveniente para abordar la historia del derecho.

PEEK is a thermoplastic polymer with halfcrystallic structure – the scientific name of this material is poly(oxy- 1,4-phenylene-oxy-1,4-phenylenecarbonyl-1,4-phenylene). It has a high melt and glass transition temperatures (Tm = 340 oC, Tg = 143 oC), high chemical resistance and is melt processable. Thus it has been used in a variety of structural and insulation applications. Nowadays, one of them is the biomedical application. The mechanical properties of PEEK have been extensively investigated in many research papers. However, there is not so high number of papers devoted to the fracture susceptibility of PEEK-material. Therefore, the the aim of this work is to present the results of studies on PEEK material with the use of fracture toughness test and digital image correlation. In order to conduct the tests, there were used two types of samples: SENB and CT. In comparison with other polymeric materials subjected to biomedical application, PEEK material presents relatively good fracture resistance with their biocompatibility.

Antibiotic resistance of Helicobacter pylori, a spiral bacterium associated with gastric diseases, is a topic that has been intensively discussed in last decades. Recent discoveries indicate promising antimicrobial and antibiotic-potentiating properties of sertraline (SER), an antidepressant substance. The aim of the study, therefore, was to determine the antibacterial activity of SER in relation to antibiotic-sensitive and antibiotic-resistant H. pylori strains. The antimicrobial tests were performed using a diffusion-disk method, microdilution method, and time-killing assay. The interaction between SER and antibiotics (amoxicillin, clarithromycin, tetracycline, and metronidazole) was determined by using a checkerboard method. In addition, the study was expanded to include observations by light, fluorescence, and scanning electron microscopy. The growth inhibition zones were in the range of 19−37 mm for discs impregnated with 2 mg of SER. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) counted for 2−8 µg/mL and 4−8 µg/mL, respectively. The time-killing assay showed the time-dependent and concentration-dependent bactericidal activity of SER. Bacteria exposed to MBCs (but not sub-MICs and MICs ≠ MBCs) underwent morphological transformation into coccoid forms. This mechanism, however, was not protective because these cells after a 24-h incubation had a several-fold reduced green/red fluorescence ratio compared to the control. Using the checkerboard assay, a synergistic/additive interaction of SER with all four antibiotics tested was demonstrated. These results indicate that SER may be a promising anti-H. pylori compound.

Nanoparticles are finding increasing applications in diagnostics, imaging and therapeutics in medicine. Iron oxide nanoparticles (IONs) have received significant interest of scientific community due to their distinctive properties. For the first time, we have delivered IONs into germ cells in any species. Our results showed that sturgeon primordial germ cells (PGCs) delivered with IONs could be detected until seven days post fertilization (dpf) under fluorescent microscope and at 22 dpf by micro-CT. Delivery of IONs into cells could be helpful for studying germ cell biology and the improvement of germ cell-based bio-technologies as isolation of PGCs using magnetic activated cell sorting or application of hyperthermia for a host sterilization purpose. Intriguingly, in our study, we did not find any toxic effects of IONs on the survival and hatching rates of sturgeon embryos when compared with embryos injected with FITC-dextran only.

Sturgeons also known as living fossils are facing threats to their survival due to overfishing and interference in natural habitats. Sterlet (Acipenser ruthenus) due to its rapid reproductive cycle and small body size can be used as a sterile host for surrogate production for late maturing and large sturgeon species. Dead end protein (dnd1) is essential for migration of Primordial Germ Cells (PGCs), the origin of all germ cells in developing embryos. Knockout or knockdown of dnd1 can be done in order to mismigrate PGCs. Previously we have used MO and UV for the aforementioned purpose, and in our present study we have used CRISPR/Cas9 technology to knockout dnd1. No or a smaller number of PGCs were detected in crispants, and we also observed malformations in some CRISPR/Cas9 injected embryos. Furthermore, we compared three established methods to achieve sterility in sterlet, and we found higher embryo survival and hatching rates in CRISPR/Cas9, UV and MO, respectively.

We describe a new nonlinear dynamic model of insect phototransduction using a NLN (nonlinear, linear, nonlinear) block structure. The first nonlinear stage provides a single exponential decline in gain and mean following the start of light stimulation. The linear stage uses a two-parameter log-normal convolution model previously applied alone to insect photoreceptors. The final stage is a static quadratic function. The model fitted current and voltage responses of isolated single photoreceptors from three different insect species with reasonable fidelity when they were stimulated by naturalistic time series having wide bandwidth and contrast, over a light intensity range of greater than 1:104. Mean squared error values for receptor current and receptor potential varied over approximately 2-60%, with many values below 10%. Linear log-normal filter parameters did not vary strongly with species or light intensity. Initial gain reduction was only large for the highest light levels, while the time constant of gain and mean reduction decreased with light intensity. The final nonlinearity changed from positively to negatively quadratic with increasing light intensity, indicating a change from threshold, or expansion to saturating compression with greater signal strength. Photoreceptor information transmission was estimated by linear information capacity and signal entropy measurements of both experimental data and predicted outputs of the model for identical stimuli at each light level. Comparison of actual and predicted data indicated significant added noise during phototransduction, with information being progressively lost by nonlinear behavior with increasing light intensity.

In this work, we studied similarities and differences between 70% ethanol in water extract (70EE) and essential oils (EOs) obtained from propolis, black poplars (Populus nigra L.) and aspens (P. tremula L.) to ascertain which of these is a better indicator of the plant species used by bees to collect propolis precursors. Composition of 70EE was analyzed by UPLC-PDA-MS, while GC-MS was used to research the EOs. Principal component analyses (PCA) and calculations of Spearman’s coefficient rank were used for statistical analysis. Statistical analysis exhibited correlation between chemical compositions of propolis and Populus buds’ 70EE. In the case of EOs, results were less clear. Compositions of black poplars, aspens EOs and propolises have shown more variability than 70EE. Different factors such as higher instability of EOs compared to 70EE, different degradation pattern of benzyl esters to benzoic acid, differences in plant metabolism and bees’ preferences may be responsible for these phenomena. Our research has therefore shown that 70EE of propolis reflected the composition of P. nigra or complex aspen–black poplar origin.

Models represent their target systems in one way or another. But what does it mean for a model to represent something beyond itself? This paper details different aspects of this problem and argues that the semantic view of theories does not provide us with an adequate response to any of these.

The methods and constructions of category theory are suitable tools for studying quantum structures and generalized probability. The aim of the present paper is to support our claim via several examples and to motivate further research in this area.

Mitochondrial energy metabolism declines during aging. PGC-1α is a transcription coactivator that plays a key role in the regulation of energetic metabolism and mitochondrial biogenesis in the cells. The aim of this study was to compare the PPARGC1A gene expression level in normal human dermal fibroblasts (NHDF) derived from young and old donors. A PGC-1α-derived peptide was then synthetized and its ability to affect the PPARGC1A gene expression and mitochondrial function was tested. We assessed changes in PPARGC1A gene expression using quantitative RT-PCR. The effect of the PGC-1α-derived peptide on energy production was determined using an ATP bioluminescent assay kit. We also studied changes in mitochondrial membrane potential using JC-1 fluorescent dye and the level of reactive oxygen species (ROS) using DCFH-DA dye in NHDF cells after UVA/B irradiation alone and in combination with a peptide treatment. The PPARGC1A gene expression decreased in an aged human dermal fibroblast. The PGC-1α-derived peptide was synthetized and increased the PPARGC1A gene expression and ATP levels in cells. Furthermore, the mitochondrial membrane potential in UVA/B irradiated cells treated with the tested PGC-1α-derived peptide was increased compared to irradiated controls. Moreover, the ROS levels in UVA/B irradiated cells treated with the PGC-1α-derived peptide decreased. On the basis of our results, PGC-1α emerges as an interesting target to combat decreasing energetic metabolism in aging skin cells. Indeed, the PGC-1α-derived peptide increasing the PPARGC1A gene expression improved the mitochondrial function and increased energy production in the cells.

Assessments of ecosystem services (ES), that aim at informing decisions on land management, are increasing in number around the globe. Despite selected success stories, evidence for ES information being used in decision making is weak, partly because ES assessments are found to fall short in targeting information needs by decision makers. To improve their applicability in practice, we compared existing concepts of ES assessments with focus on informing land use decisions and identified opportunities for enhancing the relevance of ES assessments for decision making. In a process of codesign, building on experience of four projects in Brazil, China, Madagascar, and Vietnam, we developed a step-wise approach for better targeting ES assessments toward information needs in land use decisions. Our problem-oriented approach aims at (1) structuring ES information according to land use problems identified by stakeholders, (2) targeting context-specific ES information needs by decision makers, and (3) assessing relevant management options. We demonstrate how our approach contributes to making ES assessments more policy relevant and enhances the application of ES assessments as a tool for decision support.

Abstract Background Promising clinical data and significant antigen-sparing have been demonstrated for a pandemic H5N1 influenza split-virion vaccine adjuvanted with AS03A, an α-tocopherol-containing oil-in-water emulsion-based Adjuvant System. Although studies using this formulation have been reported, there have been no data for Japanese populations. This study therefore aimed to assess the immunogenicity and tolerability of a prepandemic (H5N1) influenza vaccine adjuvanted with AS03A in Japanese adults. Methods This open-label, single-group study was conducted at two centres in Japan in healthy Japanese males and females aged 20-64 years (n = 100). Subjects received two doses of vaccine, containing 3.75 μg haemagglutinin of the A/Indonesia/5/2005-like IBCDC-RG2 Clade 2.1 (H5N1) strain adjuvanted with AS03A, 21 days apart. The primary endpoint evaluated the humoral immune response in terms of H5N1 haemagglutination inhibition (HI) antibody titres against the vaccine strain (Clade 2.1) 21 days after the second dose. Ninety five percent confidence intervals for geometric mean titres, seroprotection, seroconversion and seropositivity rates were calculated. Secondary and exploratory endpoints included the assessment of the humoral response in terms of neutralising antibody titres, the response against additional H5N1 strains (Clade 1 and Clade 2.2), as well as the evaluation of safety and reactogenicity. Results Robust immune responses were elicited after two doses of the prepandemic influenza vaccine adjuvanted with AS03A. Overall, vaccine HI seroconversion rates and seroprotection rates were 91% 21 days after the second vaccination. This fulfilled all regulatory acceptance criteria for the vaccine-homologous HI antibody level. A substantial cross-reactive humoral immune response was also observed against the virus strains A/turkey/Turkey/1/2005 (Clade 2.2) and A/Vietnam/1194/2004 (Clade 1) after the second vaccine administration. A marked post-vaccination response in terms of neutralising antibody titres was demonstrated and persistence of the immune response was observed 6 months after the first dose. The vaccine was generally well tolerated and there were no serious adverse events reported. Conclusions The H5N1 candidate vaccine adjuvanted with AS03A elicited a strong and persistent immune response against the vaccine strain A/Indonesia/5/2005 in Japanese adults. Vaccination with this formulation demonstrated a clinically acceptable reactogenicity profile and did not raise any safety concerns in this population. Trial registration Clinicaltrials.gov NCT00742885

Abstract Background Guidelines established for the treatment of HIV-1 infection and genotype interpretation do not apply for HIV-2. Data about antiretroviral (ARV) drug efficacy and resistance mutations is scarce. Methods Clinical data about HIV-2 infected patients in Belgium and Luxembourg were collected and the effect of ARV therapy on plasma viral load and CD4 counts were analysed. Viral RNA encoding for protease (PR) and reverse transcriptase (RT) from ARV-naïve and treated patients were sequenced. Results Sixty-five HIV-2 infected patients were included in this cohort. Twenty patients were treated with 25 different ARV combinations in a total of 34 regimens and six months after the start of ARV therapy, only one third achieved viral load suppression. All of these successful regimens bar one contained protease inhibitors (PIs). Mean CD4 gains in the group of viral load suppressors and the group of patients treated with PI-containing regimens were respectively significantly higher than in the group of non-suppressors and the group of PI-sparing regimens. The most frequent mutations selected under therapy (compared to HIV-2 ROD) were V71I, L90M and I89V within PR. Within RT, they were M184V, Q151M, V111I and K65R. All of these mutations, except K65R and M184V, were also found in variable proportions in ARV-naïve patients. Conclusion Despite a high rate of ARV treatment failure, better virological and immunological results were achieved with PI-containing regimens. The analysis of polymorphic positions and HIV-2 specific mutations selected during therapy showed for the first time that transmission of drug resistant viruses has occurred in Belgium and Luxembourg. The high heterogeneity in ARV combinations reflects a lack of guidelines for the treatment of HIV-2 infection.

While pandemics have long been a topic of discussion in public health, COVID-19 placed healthcare leaders in a completely new and challenging situation. This qualitative study sought to understand the personal experiences of healthcare professionals in leadership roles at the beginning of the COVID-19 pandemic. Sixteen in-depth interviews were conducted and recorded via Zoom. Most participants were men ( n = 8, 57.1%) and had a doctorate or master's degree ( n = 8, 57.1%). The themes of mental health, dynamic infrastructure, and transformative experience emerged from our participants' narratives. Most respondents reported heightened stress during that time and shared the institutional and personal mechanisms they used to deal with the situation. They were proud of their profession and their work. They discussed the "dynamic infrastructure" they experienced at the time that helped them lead. Feeling overworked was a common experience for them. Most considered leading during COVID-19 a "transformative experience" that taught them valuable lessons. They also witnessed acts of heroism as their colleagues continued to work during difficult times, even though some succumbed to COVID-19. Despite all the challenges and uncertainties healthcare professionals in leadership positions faced at the onset of COVID-19, their resilience, dedication, and commitment to their profession prevailed. In conclusion, the firsthand experiences recounted by healthcare leaders in this study shed light on the multifaceted nature of leadership during a global health crisis. Their unwavering resilience, dedication, and commitment stand as a testament to the fortitude required in such demanding circumstances. As the COVID-19 pandemic continues to evolve, the insights gleaned from this research bear significant implications for informing future strategies and support systems aimed at bolstering healthcare leadership worldwide.

Importance: The effectiveness of goal-directed care to reduce loss of brain-dead potential donors to cardiac arrest is unclear., Objective: To evaluate the effectiveness of an evidence-based, goal-directed checklist in the clinical management of brain-dead potential donors in the intensive care unit (ICU)., Design, Setting, and Participants: The Donation Network to Optimize Organ Recovery Study (DONORS) was an open-label, parallel-group cluster randomized clinical trial in Brazil. Enrollment and follow-up were conducted from June 20, 2017, to November 30, 2019. Hospital ICUs that reported 10 or more brain deaths in the previous 2 years were included. Consecutive brain-dead potential donors in the ICU aged 14 to 90 years with a condition consistent with brain death after the first clinical examination were enrolled. Participants were randomized to either the intervention group or the control group. The intention-to-treat data analysis was conducted from June 15 to August 30, 2020., Interventions: Hospital staff in the intervention group were instructed to administer to brain-dead potential donors in the intervention group an evidence-based checklist with 13 clinical goals and 14 corresponding actions to guide care, every 6 hours, from study enrollment to organ retrieval. The control group provided or received usual care., Main Outcomes and Measures: The primary outcome was loss of brain-dead potential donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed the effect of adherence to the checklist in the intervention group., Results: Among the 1771 brain-dead potential donors screened in 63 hospitals, 1535 were included. These patients included 673 males (59.2%) and had a median (IQR) age of 51 (36.3-62.0) years. The main cause of brain injury was stroke (877 [57.1%]), followed by trauma (485 [31.6%]). Of the 63 hospitals, 31 (49.2%) were assigned to the intervention group (743 [48.4%] brain-dead potential donors) and 32 (50.8%) to the control group (792 [51.6%] brain-dead potential donors). Seventy potential donors (9.4%) at intervention hospitals and 117 (14.8%) at control hospitals met the primary outcome (risk ratio [RR], 0.70; 95% CI, 0.46-1.08; P = .11). The primary outcome rate was lower in those with adherence higher than 79.0% than in the control group (5.3% vs 14.8%; RR, 0.41; 95% CI, 0.22-0.78; P = .006)., Conclusions and Relevance: This cluster randomized clinical trial was inconclusive in determining whether the overall use of an evidence-based, goal-directed checklist reduced brain-dead potential donor loss to cardiac arrest. The findings suggest that use of such a checklist has limited effectiveness without adherence to the actions recommended in this checklist., Trial Registration: ClinicalTrials.gov Identifier: NCT03179020.

Araçá is a native Brazil fruit, and has two morphological types, yellow and red; however, it is still little consumed by the population. Although there are few studies on the araçá fruit, some phytochemical propriety benefits have been described for this plant, such as antioxidant effects. To explore the benefits of araçá fruit, the physicochemical characteristics and in vitro toxicological effects of red and yellow araçá fruit were evaluated. In this work, the toxicity of araçá extracts in NIH/3T3 cell lines, the antiproliferative effects in cancer cell lines (C6, HT-29, and DU149), and the overall antifungal effects were evaluated. The irritant potential of araçá extracts was assessed by the HET-CAM test. The results demonstrated that the fruits are rich in fiber content and showed high phenols content. In addition, the araçá extracts had no present toxicity effects in cell lines; however, the red araçá extracts showed antiproliferative effects in HT-29 cancer cells at 50 mg/mL. The antifungal effects of araçá extract were promising in 23 isolates of Candida spp., and both araçá extracts showed no irritant effects. Therefore, this study demonstrated that red and yellow araçá fruit extract has promising biological and pharmacological effects that should be further explored.

This article introduces DUIA, the Database on Urban Inequality and Amenities. DUIA includes data on the socio-economic development and amenities of 86 cities. The database especially covers cities outside the West, providing new opportunities for comparative research in fields suffering from a dearth of data. DUIA addresses three concerns that have not been resolved by other databases on cities. First, we draw upon remote sensing derived data from the Atlas of Urban Expansion to more accurately define city boundaries. Second, we draw upon survey data stored in IPUMS (Integrated Public Use Microdata Series) to include extensive, harmonized, and disaggregated data. Third, we use open source software and share our scripts to ensure transparency and replicability. DUIA includes information on dwelling and household characteristics, educational attainment, ownership of assets and appliances, and access to amenities. We provide illustrative analyses on asset inequality and water access to demonstrate the potential for the database. Although we also identify several limitations, DUIA represents a step forward in the systematic study of inequality and amenities over time and across cities., Competing Interests: The authors have declared that no competing interests exist.

Gold mining is the largest source of mercury (Hg) pollution worldwide. The discharge of mercury in the environment bears direct human health risks and is likely to increase cascading effects throughout local food chains. In the Peruvian Amazon the mining process consists of slashing and burning trees, followed by extraction of gold-bearing sediment, amalgamation with Hg and gold recovery, leading each year to the degradation of 6,000-10,000 ha and the release of 180 metric tons of Hg per year to the enviroment. The purpose of this study was to determine soil Hg levels in soils of abandoned alluvial gold mine spoils and undisturbed forest in the Madre de Dios region, the epicenter of alluvial gold mining in Peru. We selected gold mine spoils of the two most important technologies locally applied for gold extraction, i.e., Minimally Mechanized Mining (MMM) and Highly Mechanized Mining (HMM), in the native communities of Laberinto and Kotzimba, respectively. We collected 127 and 35 soil samples (0-20cm depth) from potentially contaminated sites and undisturbed forest, respectively. Physicochemical analysis and determination of Hg levels were determined for all soil samples. None of the samples had Hg concentrations above Peruvian, Canadian and British Environmental Quality Standards for Agricultural Soil (6.6mg/kg). Hg levels in MMM and HMM were not significantly different between the two areas. The main variables explaining variation of soil Hg concentrations were the vegetation cover, soil organic matter, soil pH and clay particle content, which explained up to 80% of data set variation. Surprisingly, highest Hg concentrations were found in untouched old-growth forest bordering the mine spoils, but there was also a trend of increasing Hg concentrations with the regenerating vegetation. Our findings suggest that Hg concentrations in old mine spoils are low and shouldn't stand in the way of efforts to restore soil conditions and develop sustainable land uses. However, it is urgent to end the use of Hg in mining operation to decrease human and environmental risks., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: There is an increasing demand for multi-organ donors for organ transplantation programmes. This study protocol describes the Donation Network to Optimise Organ Recovery Study, a planned cluster randomised controlled trial that aims to evaluate the effectiveness of the implementation of an evidence-based, goal-directed checklist for brain-dead potential organ donor management in intensive care units (ICUs) in reducing the loss of potential donors due to cardiac arrest., Methods and Analysis: The study will include ICUs of at least 60 Brazilian sites with an average of ≥10 annual notifications of valid potential organ donors. Hospitals will be randomly assigned (with a 1:1 allocation ratio) to the intervention group, which will involve the implementation of an evidence-based, goal-directed checklist for potential organ donor maintenance, or the control group, which will maintain the usual care practices of the ICU. Team members from all participating ICUs will receive training on how to conduct family interviews for organ donation. The primary outcome will be loss of potential donors due to cardiac arrest. Secondary outcomes will include the number of actual organ donors and the number of organs recovered per actual donor., Ethics and Dissemination: The institutional review board (IRB) of the coordinating centre and of each participating site individually approved the study. We requested a waiver of informed consent for the IRB of each site. Study results will be disseminated to the general medical community through publications in peer-reviewed medical journals., Trial Registration Number: NCT03179020; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Researchers are working on key issues in regenerative medicine in many of the over 280 academic institutions in Germany. Moreover, nonuniversity research institutions such as Helmholtz-, Max-Planck-, Fraunhofer- and Leibniz-Centers provide important contributions to the field of regenerative medicine in Germany. Research on stem cells is conducted in the area of pluripotent stem cells (in particular basic research on induced pluripotent stem [iPS] cells, but also embryonic stem cells) and adult (tissue-specific) stem and progenitor cells, as well as cancer stem cells (both on basic science and translational levels).