Steerable DROP-IN radioguidance during minimal-invasive non-robotic cervical and endometrial sentinel lymph node surgery.

PURPOSE: The recently introduced tethered DROP-IN gamma probe has revolutionized the way robotic radioguided surgery is performed, fully exploiting the nature of steerable robotic instruments. Given this success, the current first-in-human study investigates if the DROP-IN can also provide benefit in combination with steerable non-robotic instruments during conventional laparoscopic surgery, showing equivalence or even benefit over a traditional rigid gamma probe. METHODS: The evaluation was performed in ten patients during laparoscopic cervical (n = 4) and endometrial (n = 6) cancer sentinel lymph node (SLN) procedures. Surgical guidance was provided using the hybrid, or bi-modal, SLN tracer ICG-99mTc-nanocolloid. SLN detection was compared between the traditional rigid laparoscopic gamma probe, the combination of a DROP-IN gamma probe and a steerable laparoscopic instrument (LaproFlex), and fluorescence imaging. RESULTS: The gynecologists experienced an enlarged freedom of movement when using the DROP-IN + LaproFlex combination compared to the rigid laparoscopic probe, making it possible to better isolate the SLN signal from background signals. This did not translate into a change in the SLN find rate yet. In both cervical and endometrial cancer combined, the rigid probe and DROP-IN + LaproFlex combination provided an equivalent detection rate of 96%, while fluorescence provided 85%. CONCLUSION: We have successfully demonstrated the in-human use of steerable DROP-IN radioguidance during laparoscopic cervical and endometrial cancer SLN procedures, expanding the utility beyond robotic procedures. Indicating an improved surgical experience, these findings encourage further investigation and consideration on a path towards routine clinical practice and improved patient outcome. TRIAL REGISTRATION: HCB/2021/0777 and NCT04492995; https://clinicaltrials.gov/study/NCT04492995.

Epidemiology of measles in Angola: Results from routine surveillance from 2015 to 2021.

Background: Measles, an acute infectious disease of extremely contagious viral aetiology, has been eliminated in some parts of the world. To the best of the authors' knowledge, this is the first study on the epidemiological pattern of the measles virus in Angola, and it was carried out through a review of 7 years of observational retrospective data from the national measles laboratory surveillance programme. Methods: A retrospective study using national databases on the laboratory surveillance of measles was performed. Patients of all ages with suspected measles from all provinces of Angola were included. Serum samples were used to detect IgM-type measles-virus-specific antibodies by enzyme-linked immunosorbent assay. Findings: In total, 3690 suspected measles samples were sent to the Instituto Nacional de Investigação em Saúde. There were 962 (26.1%) laboratory-confirmed cases, and the most affected age group was children aged 1-4 years. The highest incidence rate per 100,000 population was found in Benguela (17.9%), followed by Huambo (16.7%) and Cuanza Sul (13.6%). Of the study years, the incidence rate per 1,000,000 population was highest in 2020 (11.9%). The most common complication was diarrhoea (n=406, 42.2%). Of the confirmed cases, 209 (21.7%) were vaccinated, 633 (65.8%) were unvaccinated, and 120 (12.5%) had unknown vaccination status. For all study years, vaccination coverage was <70%. Interpretation: Measles continues to be a serious problem in Angola, and more efforts are needed to increase measles surveillance and achieve a high percentage of vaccination coverage.

The use of copper isotopes for understanding metal transfer mechanisms within the continuum mine-river-dam (Huelva Region, Spain).

Mining areas and in particular those containing massive sulfides have left a heavy environmental legacy with soils and hydrographic networks highly contaminated with metals and metalloids as for example in the Iberian Pyrite Belt (Huelva, Spain). Here, we present new data on copper (Cu) isotopic composition of waters and solids collected along a continuum Mine (Tharsis)-River (Meca)-Lake (Sancho) in the Iberian Pyrite Belt. Our results show that the isotopic signature of pit lakes is spatially variable, but remains stable over the seasons; this signature seems to be controlled by water-rock interaction processes. The data obtained on the Meca River imply a number of attenuation processes such as decrease in the metal concentration by precipitation of secondary minerals. This is accompanied by preferential retention of the heavy isotope (65Cu) with a possibility of living organisms (e.g., algae) participation. The terminal Sancho lake demonstrated constant isotopic signature over the entire depth of the water column despite sizable variations in Cu concentrations, which can be tentatively explained by a superposition of counter-interacting biotic and abiotic processes of Cu fractionation. Overall, the understanding of the isotopic variations along the hydrological continuum is useful for a better understanding of metal element transfer within mining environments and surrounding surface waters.

Acid Mine Drainage Effects in the Hydrobiology of Freshwater Streams from Three Mining Areas (SW Portugal): A Statistical Approach.

Aljustrel, Lousal and S. Domingos mines are located in the Iberian Pyrite Belt (IPB), one of the greatest massive sulfide ore deposits worldwide. These mines' surrounding streams are affected by Acid Mine Drainage (AMD). The main purpose of this study was to understand AMD influence in the water quality and diatom behavior. Thus, waters and diatoms were sampled in 6 sites from the 3 selected mines on winter and summer of 2016. The highest concentrations were found in acidic sites: A3 (Aljustrel-Al, Cd, Cu, Fe and Zn (and lowest pH)) and L1 (Lousal-As, Mn, Ca, Mg, SO42- and conductivity). The most abundant diatom species was Pinnularia aljustrelica with 100% of dominance in A3 and S1 acidic sites, which puts in evidence this species adaptation to AMD harsh conditions. Multivariate cluster analysis allowed us to reinforce results from previous studies, where spatial differences were more relevant than seasonal ones. In 12 years (2004-2016), and with many transformations undertaken (re-opening and rehabilitation), there is a conservative behavior in the biological species (diatoms) and physicochemical concentrations (metals, pH and sulfates) from these three mining sites. This type of biogeochemical diagnosis is necessary for the sustainable use of these waters and the prevention of the polluting process, aimed to protect the water ecosystem and its biodiversity.

Biogeochemical indicators (waters/diatoms) of acid mine drainage pollution in the Odiel river (Iberian Pyritic Belt, SW Spain).

Odiel river basin is located in the Iberian Pyritic Belt (IPB) and mostly of its tributaries are severely affected by acid mine drainage (AMD). It is originated when pyritic minerals from abandoned mines, especially mineral residues from waste rock dams, get in contact with air and water. Fifteen sampling points were chosen to analyze interactions between diatom communities and water hydrogeochemistry. Considering physicochemical characteristics, sampling points were assigned as highly, moderately, and unpolluted by AMD. No correlation was observed between ecological diversity indexes and physico-chemical parameters. However, a dependency relationship between diatom species distribution and specific pH, conductivity, redox potential, sulfate, and metal concentrations was observed. Cluster analysis based on Pearson correlation and rs values of the non-parametric Spearman correlation allowed to identify Pinnularia acidophila, Pinnularia subcapitata var. elongata, and Eunotia exigua as the main bioindicators of AMD-polluted Odiel streams. Finally, a principal component analysis led to associate the most abundant diatoms species to specific physico-chemical parameters.

Odiel River (SW Spain), a Singular Scenario Affected by Acid Mine Drainage (AMD): Graphical and Statistical Models to Assess Diatoms and Water Hydrogeochemistry Interactions.

The Odiel River (SW Spain) is one of the most cited rivers in the scientific literature due to its high pollution degree, generated by more than 80 sulphide mines' (mostly unrestored) contamination in the Iberian Pyritic Belt (IPB), that have been exploited for more than 5000 years. Along the river and its tributaries, the physico-chemical parameters and diatoms, from 15 sampling points, were analyzed in the laboratory. Physico-chemical parameters, water chemical analysis, together with richness and Shannon-Wiener indexes were integrated in a matrix. An initial graphical treatment allowed the definition and proposal of a functioning system model, as well as the establishment of cause-effect relationships between pollution and its effects on biota. Then, the proposed model was statistically validated by factor analysis. For acidic pH waters, high values of Eh, TDS, sulphate, ∑REE and ∑Ficklin were found, while diatomologic indicators took low values. Thus, factor analysis was a very effective tool for graphical treatment validation as well as for pollution-biota interaction models' formulation, governed by two factors: AMD processes and water balance suffered by the studied river. As a novelty, the cause-effect relationships between high barium concentration and low diversity and richness were demonstrated in the IPB, for the first time.

Application of a Fuzzy Logic Based Methodology to Validate the Hydrochemical Characterization and Determining Seasonal Influence of a Watershed Affected by Acid Mine Drainage.

The Odiel River Basin, located in the Iberian Pyrite Belt (IPB), is heavily affected by acid mine drainage (AMD), which occurs when pyritic minerals from sulfide mining areas are exposed to atmospheric, hydrological or biological weathering. This paper presents a hydrochemical characterization of parameters in the Odiel River Basin by means of Fuzzy Logic and data mining methodologies to determine the seasonal influence of AMD in polluted waters that have not been used before for a basin in this environmental area. This technique was proven to be effective, providing results that could not be achieved by using classic statistics, because it allows us to characterize the different parameters separately and also their relationships in waters affected by AMD in a qualitative manner based on the antecedents and according to the conditions (rules) imposed by the consequents (in this case, the Fe(II) and accumulated rainfall over 30 days). Thus, it was possible to confirm that hydrochemistry is greatly affected by seasonal changes, with a higher pH in the wet season (up to 8.59) compared to 2.12, the minimum pH value reached in the dry season. Accordingly, higher concentrations of most of the metals were observed in the dry season (e.g., up to 4000 mg/L of Fe (II)), with the exception of the values found after the first rains that occur in the early fall. With the use of the Fuzzy Logic technique, it was observed that, during the wet season, lixiviates with a higher Fe content have higher metal concentrations, and in the dry season, the behavior is the opposite.

Acid Mine Drainage as Energizing Microbial Niches for the Formation of Iron Stromatolites: The Tintillo River in Southwest Spain.

The Iberian Pyrite Belt in southwest Spain hosts some of the largest and diverse extreme acidic environments with textural variation across rapidly changing biogeochemical gradients at multiple scales. After almost three decades of studies, mostly focused on molecular evolution and metagenomics, there is an increasing awareness of the multidisciplinary potential of these types of settings, especially for astrobiology. Since modern automatized exploration on extraterrestrial surfaces is essentially based on the morphological recognition of biosignatures, a macroscopic characterization of such sedimentary extreme environments and how they look is crucial to identify life properties, but it is a perspective that most molecular approaches frequently miss. Although acid mine drainage (AMD) systems are toxic and contaminated, they offer at the same time the bioengineering tools for natural remediation strategies. This work presents a biosedimentological characterization of the clastic iron stromatolites in the Tintillo river. They occur as laminated terraced iron formations that are the most distinctive sedimentary facies at the Tintillo river, which is polluted by AMD. Iron stromatolites originate from fluvial abiotic factors that interact with biological zonation. The authigenic precipitation of schwertmannite and jarosite results from microbial-mineral interactions between mineral and organic matrices. The Tintillo iron stromatolites are composed of bacterial filaments and diatoms as Nitzschia aurariae, Pinnularia aljustrelica, Stauroneis kriegeri, and Fragilaria sp. Furthermore, the active biosorption and bioleaching of sulfur are suggested by the black and white coloration of microbial filaments inside stromatolites. AMD systems are hazardous due to physical, chemical, and biological agents, but they also provide biogeochemical sources with which to infer past geochemical conditions on Earth and inform exploration efforts on extraterrestrial surfaces in the future.

Physico-Chemical Influence of Surface Water Contaminated by Acid Mine Drainage on the Populations of Diatoms in Dams (Iberian Pyrite Belt, SW Spain).

Twenty-three water dams located in the Iberian Pyrite Belt were studied during March 2012 (early spring) in order to carry out an environmental assessment based on diatom communities and to define the relationships between these biological communities and the physico-chemical characteristics of the dam surface water. This is the first time that a diatom inventory has been done for dams affected by acid mine drainage (AMD) in the Spanish part of the Iberian Pyrite Belt (IPB). It was found that the pH was the main factor influencing the behaviour of the diatom communities. Then, using a dbRDA approach it was possible to organize the aggrupation of diatoms into four groups in response to the physico-chemical conditions of the ecosystem, especially pH: (1) Maris, Aac, Gos, Cmora (pH 2-3); (2) Andc, San, And, Dpin (pH 3-4.5); (3) Gran, Pleon, Oliv, Lagu, Chan, SilI, SilII, Joya, Gar, Agrio, Camp, Corum (pH 4.5-6); (4) Herr, Diq I, Diq II (pH 6-7). The obtained results confirmed the response of benthic diatom communities to changes in the physico-chemical characteristics of surface water, and helped to understand the role of diatoms as indicators of the degree of AMD contamination in those 23 dams. Special attention was given to those that have an acidophilic or acid-tolerant profile (pH 2-3 and pH 3-4.5) such as Pinnularia aljustrelica, Pinnularia acidophila, Pinnularia acoricola and Eunotia exigua, which are the two groups found in the most AMD contaminated dams.

The UNESCO national biosphere reserve (Marismas del Odiel, SW Spain): an area of 18,875 ha affected by mining waste.

At the mouth of the Odiel River, within the Natural Area "Marismas del Odiel", there has been for years a collection of waste from different mining sites. In the present work, an approach has been made to the problem that this supposes, quantifying the pollutants that are poured into the estuary from the mineral collection located on the banks of the river. The study carried out has been able to determine high metal concentrations, comparable with any rubble from the upstream mines, with pH value of 1.66, lower than many other areas affected by acid mine drainage in the same river, and even with concentrations of Fe and As higher than those provided by the rest of the mining facilities of the Odiel basin. This can make us understand the serious situation of the Natural Park, where a great variety of birds and plants of special ecological interest are located.

Integrating CRISPR-Cas9 Technology into Undergraduate Courses: Perspectives from a National Science Foundation (NSF) Workshop for Undergraduate Faculty, June 2018.

As CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 technology becomes more mainstream in life science research, it becomes critical for undergraduate instructors to devise engaging ways to bring the technology into their classrooms. To help meet this challenge, the National Science Foundation sponsored a workshop for undergraduate instructors in June 2018 at The Ohio State University in conjunction with the annual Association of Biology Laboratory Educators meeting based on a workflow developed by the workshop's facilitators. Over the course of two and a half days, participants worked through a modular workflow for the use of CRISPR-Cas9 in a course-based (undergraduate) research experience (CURE) setting while discussing the barriers each of their institutions had to implementing such work, and how such barriers could be overcome. The result of the workshop was a team with newfound energy and confidence to implement CRISPR-Cas9 technology in their courses and the development of a community of undergraduate educators dedicated to supporting each other in the implementation of the workflow either in a CURE or modular format. In this article, we review the activities and discussions from the workshop that helped each participant devise their own tailored approaches of how best to bring this exciting new technology into their classes.

Biogeochemical characterization of surface waters in the Aljustrel mining area (South Portugal).

Aljustrel mining area (South Portugal) is a part of the Iberian Pyrite Belt and encloses six sulfide mineral masses. This mine is classified of high environmental risk due to the large tailings' volume and acid mine drainage (AMD)-affected waters generated by sulfides' oxidation. The use of biological indicators (e.g., diatoms) revealed to be an important tool to address the degree of AMD contamination in waters. Multivariate analysis has been used as a relevant approach for the characterization of AMD processes. Cluster analysis was used to integrate the significant amount and diversity of variables (physicochemical and biological), discriminating the different types of waters, characterized by the high complexity occurring in this region. The distinction of two main marked phenomena was achieved: (1) the circumneutral-Na-Cl water type (sites DA, PF, BX, BF, RO, CB), expressing the geological contributions of the Cenozoic sediments of Sado river basin, with high diatom diversity (predominating brackish diatoms as Entomoneis alata); and (2) the acid-metal-sulfated water type (sites BM, JU, RJ, AA, MR, BE, PC, AF), reflecting both the AMD contamination and the dissolution of minerals (e.g., silicates) from the hosting rocks, potentiated by the extremely low pH. This last group of sites showed lower diatom diversity but with typical diatoms from acid- and metal-contaminated waters (e.g., Pinnularia aljustrelica). In addition to these two water types, this hierarchical classification method also allowed to distinguish individual cases in subclusters, for example, treated dams (DC, DD), with alkaline substances (lime/limestone), that changed the physicochemical dynamics of the contaminated waters.

Negative pH values in an open-air radical environment affected by acid mine drainage. Characterization and proposal of a hydrogeochemical model.

This paper presents the finding of a singular environment polluted by acid mine drainage in the Iberian Pyrite Belt. This situation is regulated by particular conditions, thus the analysed values can be considered as extreme, not only because of the high concentrations of toxic elements, but also due to the extreme low pH, reaching an average negative pH of -1.56, never found before in open-air environments contaminated by acid mine drainage. Concentrations up to 59 g/L of Fe, 2.4 g/L of Al, 740 mg/L of As, 4.3 mg/L of Co, 5.3 mg/L of Ge, 4.8 mg/L of Sb, inter alia, can be found dissolved in these polluted waters. The main aims of the present work are the physicochemical characterization and the toxicity assessment of these radical polluted waters. In addition, a hydrogeochemical model of the system will be proposed, which justifies the extreme pH value and the extraordinarily high concentrations of toxic elements, even for acid mine drainage polluted environments. Extreme acidity and metal and sulphate concentrations in the Radical Environment are due to several processes of different nature, mainly driven by the geochemistry of the minerals presents in the endorheic character of the basin. The extremely acidic nature of these waters control the Fe species present in them, being FeHSO4+ the mainly Fe specie representing 94% of total. High toxicity of these waters has been detected due to the absence of any diatoms species.

Histone H2A.Z acid patch residues required for deposition and function.

The incorporation of histone variants is one mechanism used by the eukaryotic cell to alter the generally repressive chromatin template. However, the exact molecular mechanisms that direct this incorporation are not well understood. The SWR1 chromatin remodeling complex that binds to and directs incorporation of histone variant H2A.Z into chromatin has been characterized, but significantly less information is available concerning the requirements on the H2A.Z target molecule. We performed an unbiased mutagenic screen designed to elucidate the function of H2A.Z in Saccharomyces cerevisiae. The screen identified residues within the conserved acidic patch of H2A.Z as being important for the function of the variant. We characterized single point mutations in the patch that are phenotypically sensitive to a variety of growth conditions and are expressed at lower protein levels, but are functionally defective (htz1-D99A, htz1-D99K, and htz1-E101K). The mutants were significantly less detectable by chromatin immunoprecipitation at PHO5, a gene previously described to be enriched for H2A.Z. These results identify acidic patch residues of H2A.Z that are critical for mediating deposition and function in chromatin, and represent potential candidates for the interaction of H2A.Z with its deposition and/or targeting machinery.

Histone variant H2A.Z and RNA polymerase II transcription elongation.

Nucleosomes containing histone variant H2A.Z (Htz1) serve to poise quiescent genes for activation and transcriptional initiation. However, little is known about their role in transcription elongation. Here we show that dominant mutations in the elongation genes SPT5 and SPT16 suppress the hypersensitivity of htz1Δ strains to drugs that inhibit elongation, indicating that Htz1 functions at the level of transcription elongation. Direct kinetic measurements of RNA polymerase II (Pol II) movement across the 9.5-kb GAL10p-VPS13 gene revealed that the elongation rate of polymerase is 24% slower in the absence of Htz1. We provide evidence for two nonexclusive mechanisms. First, we observed that both the phospho-Ser2 levels in the elongating isoform of Pol II and the loading of Spt5 and Elongator over the GAL1 open reading frame (ORF) depend on Htz1. Second, in the absence of Htz1, the density of nucleosome occupancy is increased over the GAL10p-VPS13 ORF and the chromatin is refractory to remodeling during active transcription. These results establish a mechanistic role for Htz1 in transcription elongation and suggest that Htz1-containing nucleosomes facilitate Pol II passage by affecting the correct assembly and modification status of Pol II elongation complexes and by favoring efficient nucleosome remodeling over the gene.

Envejecimiento cutáneo / Cutaneous photoaging

El envejecimiento cutáneo es un proceso biológico complejo, progresivo e irreversible, condicionado por determinantes genéticos individuales y el acúmulo de diversas agresiones ambientales. Comprende dos procesos clínico-biológicos interdependientes que se desarrollan simultáneamente: 1) Envejecimiento entrínseco o cronológico: determinado genéticamente, afecta la piel y a todos los demás órganos a través de un deterioro tisular lento e irreversible. Respecto a la piel, representa el conjunto de alteraciones fisiopatológicas cutáneas que se producen como consecuencia del paso del tiempo. Se manifiesta por laxitud, sequedad, palidez, atrofia variable, arrugas y diversas neoformaciones benignas o malignas (tumores benignos). 2) Fotoenvejecimiento: la dermatosis fotoinducida por excelencia. Es la demostración clínica que el daño por radiación ultravioleta (UVB y UVA) es acumulativo e irreversible. Se manifiesta por modificaciones funcionales y estructurales en zonas expuestas como la cara, cuello, antebrazos, dorso de manos y escote. El grado de fotoenvejecimiento depende de factores genéticos, del fototipo y la calidad de reparación de los mecanismos del ADN. Deben incluirse aquí también diversas reacciones de fototoxicidad por medicamentos con secuelas de fotoenvejecimiento. En este trabajo se realiza una revisión de los mecanismos biológicos, bioquímicos y moleculares, la clínica, las pautas de diagnósticos y los tratamientos para el envejecimiento cutáneo. Se agregan comentarios basados en la experiencia y opinión de los autores

Envejecimiento cutáneo / Cutaneous photoaging

El envejecimiento cutáneo es un proceso biológico complejo, progresivo e irreversible, condicionado por determinantes genéticos individuales y el acúmulo de diversas agresiones ambientales. Comprende dos procesos clínico-biológicos interdependientes que se desarrollan simultáneamente: 1) Envejecimiento entrínseco o cronológico: determinado genéticamente, afecta la piel y a todos los demás órganos a través de un deterioro tisular lento e irreversible. Respecto a la piel, representa el conjunto de alteraciones fisiopatológicas cutáneas que se producen como consecuencia del paso del tiempo. Se manifiesta por laxitud, sequedad, palidez, atrofia variable, arrugas y diversas neoformaciones benignas o malignas (tumores benignos). 2) Fotoenvejecimiento: la dermatosis fotoinducida por excelencia. Es la demostración clínica que el daño por radiación ultravioleta (UVB y UVA) es acumulativo e irreversible. Se manifiesta por modificaciones funcionales y estructurales en zonas expuestas como la cara, cuello, antebrazos, dorso de manos y escote. El grado de fotoenvejecimiento depende de factores genéticos, del fototipo y la calidad de reparación de los mecanismos del ADN. Deben incluirse aquí también diversas reacciones de fototoxicidad por medicamentos con secuelas de fotoenvejecimiento. En este trabajo se realiza una revisión de los mecanismos biológicos, bioquímicos y moleculares, la clínica, las pautas de diagnósticos y los tratamientos para el envejecimiento cutáneo. Se agregan comentarios basados en la experiencia y opinión de los autores (AU)