The impact of continuous lenalidomide maintenance treatment on people living with multiple myeloma-a single-centre, qualitative service evaluation study.

PURPOSE: Continuous lenalidomide maintenance treatment after autologous stem cell transplantation delivers improvement in progression free and overall survival among newly diagnosed multiple myeloma patients and has been the standard of care in the UK since March 2021. However, there is scant information about its impact on patients' day-to-day lives. This service evaluation aimed to qualitatively assess patients receiving lenalidomide treatment at a cancer centre in London, in order that the service might better align with needs and expectations of patients. METHODS: We conducted 20 semi-structured interviews among myeloma patients who were on continuous lenalidomide maintenance treatment at a specialist cancer centre in London. Members of the clinical team identified potentially eligible participants to take part, and convenience sampling was used to select 10 male and 10 female patients, median age of 58 (range, 45-71). The median treatment duration was 11 months (range, 1-60 months). Participants were qualitatively interviewed following the same semi-structured interview guide, which was designed to explore patient experience and insights of lenalidomide. Reflexive thematic analysis was used for data analysis. RESULTS: Four overarching themes were as follows: (i) lenalidomide: understanding its role and rationale; (ii) reframing the loss of a treatment-free period to a return to normal life; (iii) the reality of being on lenalidomide: balancing hopes with hurdles; (iv) gratitude and grievances: exploring mixed perceptions of care and communication. Results will be used to enhance clinical services by tailoring communication to better meet patients' preferences when making treatment decisions. CONCLUSION: This study highlights that most patients feel gratitude for being offered continuous lenalidomide and perceive it as alleviating some fears concerning relapse. It reveals variations in side effects in different age groups; younger patients reported no/negligible side effects, whilst several older patients with comorbidities described significant symptom burden, occasionally leading to treatment discontinuation which caused distress at the perceived loss of prolonged remission. Future research should prioritise understanding the unique needs of younger patients living with multiple myeloma.

Onychocolone A produced by the fungus Onychocola sp. targets cancer stem cells and stops pancreatic cancer progression by inhibiting MEK2-dependent cell signaling.

Pancreatic cancer (PC) shows a high fatality rate that can only be faced with a combination of surgery and chemotherapy or palliative treatment in the case of advanced patients. Besides, PC tumors are enriched with subpopulations of cancer stem cells (CSCs) that are resistant to the existing chemotherapeutic agents, which raises an important need for the identification of new drugs. To fill this gap, we have tested the anti-tumoral activity of microbial extracts, which chemical diversity offers a broad spectrum of potential new bioactive compounds. Extracts derived from the fungus Onychocola sp. CF-107644 were assayed via high throughput screening followed by bioassay-guided fractionation and resulted in the identification and isolation of six benzophenone derivatives with antitumoral activity: onychocolones A-F (#1-6). The structures of the compounds were established by spectroscopic methods, including ESI-TOF MS, 1D and 2D NMR analyses and X-ray diffraction. Compounds #1-4 significantly inhibited the growth of the pancreas tumoral cell lines, with low-micromolar Median Effective Doses (ED50s). Compound #1 (onychocolone A) was prioritized for further profiling due to its pro-apoptotic effect, which was further validated on 3D spheroids and pancreatic CSCs. Protein expression assays showed that the effect was mechanistically linked to the inhibition of MEK onco-signaling pathway. The efficacy of onychocolone A was also demonstrated in vivo by the reduction of tumor growth in a pancreatic xenograft mouse model generated by CSCs. Altogether, the data support that onychocolone A is a promising new small molecule for hit-to-lead development of a new treatment for PC.

Drivers of business model innovation in family firms: A dataset analysis.

In recent years, both in the world of research and consulting, the concept of innovation in the business model has been gaining a lot of interest. As a result, an incipient number of scientific and popular publications are being generated, which try to delimit and explain this term, as well as work methodologies for its application in the business world. The family business field can benefit from the application of this approach. But, at the same time, it can also serve as an object of study since its special idiosyncrasy will allow to deepen the analysis of successful business models. To illustrate innovation in business models, data from 112 family firms representative of the regional economy are presented. The companies are also associated with the Murcian Association of Family Businesses (Amefmur). The collaboration with this organization has made it possible to obtain very valuable and representative information thanks to the support provided. The collection of information was carried out through an electronic survey. These data could be especially useful for establishing business recommendations for this type of companies and for analyzing other possible interrelationships of the variables available in the database.

A murine model for the del(GJB6-D13S1830) deletion recapitulating the phenotype of human DFNB1 hearing impairment: generation and functional and histopathological study.

Inherited hearing impairment is a remarkably heterogeneous monogenic condition, involving hundreds of genes, most of them with very small (< 1%) epidemiological contributions. The exception is GJB2, the gene encoding connexin-26 and underlying DFNB1, which is the most frequent type of autosomal recessive non-syndromic hearing impairment (ARNSHI) in most populations (up to 40% of ARNSHI cases). DFNB1 is caused by different types of pathogenic variants in GJB2, but also by large deletions that keep the gene intact but remove an upstream regulatory element that is essential for its expression. Such large deletions, found in most populations, behave as complete loss-of-function variants, usually associated with a profound hearing impairment. By using CRISPR-Cas9 genetic edition, we have generated a murine model (Dfnb1em274) that reproduces the most frequent of those deletions, del(GJB6-D13S1830). Dfnb1em274 homozygous mice are viable, bypassing the embryonic lethality of the Gjb2 knockout, and present a phenotype of profound hearing loss (> 90 dB SPL) that correlates with specific structural abnormalities in the cochlea. We show that Gjb2 expression is nearly abolished and its protein product, Cx26, is nearly absent all throughout the cochlea, unlike previous conditional knockouts in which Gjb2 ablation was not obtained in all cell types. The Dfnb1em274 model recapitulates the clinical presentation of patients harbouring the del(GJB6-D13S1830) variant and thus it is a valuable tool to study the pathological mechanisms of DFNB1 and to assay therapies for this most frequent type of human ARNSHI.

Metabolic trade-offs constrain the cell size ratio in a nitrogen-fixing symbiosis.

Biological dinitrogen (N2) fixation is a key metabolic process exclusively performed by prokaryotes, some of which are symbiotic with eukaryotes. Species of the marine haptophyte algae Braarudosphaera bigelowii harbor the N2-fixing endosymbiotic cyanobacteria UCYN-A, which might be evolving organelle-like characteristics. We found that the size ratio between UCYN-A and their hosts is strikingly conserved across sublineages/species, which is consistent with the size relationships of organelles in this symbiosis and other species. Metabolic modeling showed that this size relationship maximizes the coordinated growth rate based on trade-offs between resource acquisition and exchange. Our findings show that the size relationships of N2-fixing endosymbionts and organelles in unicellular eukaryotes are constrained by predictable metabolic underpinnings and that UCYN-A is, in many regards, functioning like a hypothetical N2-fixing organelle (or nitroplast).

Relationship between the Viral Load in Patients with Different COVID-19 Severities and SARS-CoV-2 Variants.

SARS-CoV-2 has spread throughout the world since 2019, changing in its genome and leading to the appearance of new variants. This gave it different evolutionary advantages, such as greater infectivity and/or a greater ability to avoid the immune response, which could lead to an increased severity of COVID-19 cases. There is no consistent information about the viral load that occurs in infection with the different SARS-CoV-2 variants, hence, in this study we quantify the viral load of more than 16,800 samples taken from the Mexican population with confirmed diagnosis of COVID-19 and we analyze the relation between different demographic and disease variables. We detected that the viral load caused by different variants differs only in the first two days after the onset of symptoms, being higher when infections are caused by the delta variant and lower when caused by omicron. Furthermore, the viral load appears to be higher in outpatients compared to hospitalized patients or in cases of death. On the other hand, no differences were found in the viral load produced in vaccinated and unvaccinated patients, nor did it differ between genders.

Marine picoplankton metagenomes and MAGs from eleven vertical profiles obtained by the Malaspina Expedition.

The Ocean microbiome has a crucial role in Earth's biogeochemical cycles. During the last decade, global cruises such as Tara Oceans and the Malaspina Expedition have expanded our understanding of the diversity and genetic repertoire of marine microbes. Nevertheless, there are still knowledge gaps regarding their diversity patterns throughout depth gradients ranging from the surface to the deep ocean. Here we present a dataset of 76 microbial metagenomes (MProfile) of the picoplankton size fraction (0.2-3.0 µm) collected in 11 vertical profiles covering contrasting ocean regions sampled during the Malaspina Expedition circumnavigation (7 depths, from surface to 4,000 m deep). The MProfile dataset produced 1.66 Tbp of raw DNA sequences from which we derived: 17.4 million genes clustered at 95% sequence similarity (M-GeneDB-VP), 2,672 metagenome-assembled genomes (MAGs) of Archaea and Bacteria (Malaspina-VP-MAGs), and over 100,000 viral genomic sequences. This dataset will be a valuable resource for exploring the functional and taxonomic connectivity between the photic and bathypelagic tropical and sub-tropical ocean, while increasing our general knowledge of the Ocean microbiome.

Discovery of bioactive natural products of microbial origin as inhibitors of the PD-1/PD-L1 protein-protein interaction.

The PD-1/PD-L1 protein-protein interaction (PPI) controls an adaptive immune resistance mechanism exerted by tumor cells to evade immune responses. The large-molecule nature of current commercial monoclonal antibodies against this PPI hampers their effectiveness by limiting tumor penetration and inducing severe immune-related side effects. Synthetic small-molecule inhibitors may overcome such limitations and have demonstrated promising clinical translation, but their design is challenging. Microbial natural products (NPs) are a source of small molecules with vast chemical diversity that have proved anti-tumoral activities, but which immunotherapeutic properties as PD-1/PD-L1 inhibitors had remained uncharacterized so far. Here, we have developed the first cell-based PD-1/PD-L1 blockade reporter assay to screen NPs libraries. In this study, 6000 microbial extracts of maximum biosynthetic diversity were screened. A secondary metabolite called alpha-cyclopiazonic acid (α-CPA) of a bioactive fungal extract was confirmed as a new PD-1/PD-L1 inhibitor with low micromolar range in the cellular assay and in an additional cell-free competitive assay. Thermal denaturation experiments with PD-1 confirmed that the mechanism of inhibition is based on its stabilization upon binding to α-CPA. The identification of α-CPA as a novel PD-1 stabilizer proves the unprecedented resolution of this methodology at capturing specific PD-1/PD-L1 PPI inhibitors from chemically diverse NP libraries.

Establishment of a screening platform based on human coronavirus OC43 for the identification of microbial natural products with antiviral activity.

IMPORTANCE: The COVID-19 pandemic has revealed the lack of effective treatments against betacoronaviruses and the urgent need for new broad-spectrum antivirals. Natural products are a valuable source of bioactive compounds with pharmaceutical potential that may lead to the discovery of new antiviral agents. Specifically, compared to conventional synthetic molecules, microbial natural extracts possess a unique and vast chemical diversity and are amenable to large-scale production. The implementation of a high-throughput screening platform using the betacoronavirus OC43 in a human cell line infection model has provided proof of concept of the approach and has allowed for the rapid and efficient evaluation of 1,280 microbial extracts. The identification of several active compounds validates the potential of the platform for the search for new compounds with antiviral capacity.

Tratamiento quirúrgico del pie reumático mediante artrodesis de la primera articulación metatarsofalángica y panresección metatarsal

Introducción: La artritis reumatoide resulta una enfermedad autoinmune, inflamatoria, crónica y progresiva, que afecta al aparato locomotor. Puede provocar deformidad, dolor y disminución de la función del pie. Su tratamiento puede ser conservador o quirúrgico. Objetivo: Demostrar la eficacia de la artrodesis de la primera articulación metatarsofalángica con la panresección metatarsal en el tratamiento quirúrgico del pie reumático. Presentación del caso: Se presentaron diez casos de pacientes con factor reumatoideo positivo, intervenidos mediante artrodesis de la primera articulación metatarsofalángica y panresección metatarsal. Se valoró el seguimiento posquirúrgico inmediato y al año de evolución. Tras la intervención se consiguió una media de satisfacción de la escala Likert de 9,3 y una media de la escala visual analógica de dolor de 2,0. Asimismo, disminuyeron considerablemente los ángulos hallux abductus valgus e intermetatarsal I-II. Conclusiones: La combinación de artrodesis de la primera articulación metatarsofalángica con la panresección metatarsal se aplica en este tipo de pacientes, ya que favorece la funcionabilidad del pie y aminora significativamente la sintomatología dolorosa.

Introduction: Rheumatoid arthritis is an autoimmune, inflammatory, chronic and progressive disease that affects the locomotor system. It can cause deformity, pain, and decreased function of the foot. The treatment can be conservative or surgical. Objective: To demonstrate the efficacy of arthrodesis of the first metatarsophalangeal joint with metatarsal panresection in the surgical treatment of the rheumatoid foot. Methods: Ten cases of patients with positive rheumatoid factor who underwent arthrodesis of the first metatarsophalangeal joint and metatarsal panresection were reported. Immediate post-surgical follow-up and one year of evolution were assessed. Results: After the intervention, a mean Likert scale satisfaction of 9.3 was achieved and a visual analogue pain scale mean of 2.0. Likewise, the hallux abductus valgus and intermetatarsal I-II angles decreased considerably. Conclusions: The combination of arthrodesis of the first metatarsophalangeal joint with metatarsal panresection is used in this type of patients, since it favors the functionality of the foot and significantly reduces painful symptoms.

[Telerehabilitación: evolución de la capacidad funcional, calidad de vida y salud mental en pacientes con covid-19 tras un programa de rehabilitación respiratoria.] / Telerehabilitation: Evolution of functional capacity, quality of life and mental health in COVID-19 patients after a Respiratory Rehabilitation program.

OBJECTIVE: The healthcare approach to rehabilitation has undergone important changes due to the COVID-19 pandemic. The objective of the study was to assess the role of a home respiratory telerehabilitation program based on exercises and education in patients admitted to COVID-19. METHODS: An observational cohort study of COVID-19 patients admitted to General Hospital La Mancha Centro from March to June 2020 was carried out, who were assessed and treated by the rehabilitation, physiotherapy and occupational therapy service. After hospital discharge, the functional capacity, quality of life, mental health and happiness of the patients were assessed by telephone consultation at two, fifteen and thirty days. A descriptive analysis was carried out and for follow-up the McNemar test was used for qualitative variables and Student's t or Wilcoxon paired samples test for quantitative variables. RESULTS: Thirty patients were included in the study. The mean age was 60.9 years, with 50% male and 50% female. 80% of the patients were admitted to the ICU, with a mean of thirty four days. 73.3% of the patients developed ICU-acquired weakness. There are statistically significant changes in functional capacity (Barthel from 57.5 to 90), quality of life (EQ-VAS from 60 to 70), mental health (MHI-5 from 23 to 27) and happiness (Lyubomirsky from 4 to 4.5) of patients at thirty days after discharge. CONCLUSIONS: Patients admitted for COVID-19 and included in the home respiratory rehabilitation program through telerehabilitation significantly improve their functional capacity, quality of life, mental health, and happiness during follow-up.

OBJECTIVE: El abordaje asistencial de la rehabilitación ha sufrido cambios importantes con motivo de la pandemia de la COVID-19. El objetivo del estudio fue valorar el papel de un programa de telerehabilitación respiratoria domiciliaria basada en ejercicios y educación en pacientes ingresados con COVID-19. METHODS: Se realizó un estudio observacional de una cohorte de pacientes con COVID-19 ingresados en el Hospital General La Mancha Centro desde marzo a junio de 2020, que fueron valorados y tratados por el servicio de rehabilitación, fisioterapia y terapia ocupacional. Tras el alta hospitalaria, se valoró mediante consulta telefónica a los dos, quince y treinta días, la capacidad funcional, la calidad de vida, la salud mental y la felicidad de los pacientes. Se realizó un análisis descriptivo y para el seguimiento se utilizó los test de McNemar para variables cualitativas y t de student o Wilcoxon de muestras apareados para las cuantitativas. RESULTS: Treinta pacientes fueron incluidos en el estudio. La edad media fue de 60,9 años, siendo un 50% hombres y un 50% mujeres. El 80% de los pacientes ingresaron en UCI, con una media de treinta y cuatro días. El 73,3% de los pacientes desarrollaron debilidad adquirida en UCI. Existen cambios estadísticamente significativos sobre capacidad funcional (Barthel de 57,5 a 90), calidad de vida (EVA de 60 a 70), salud mental (MHI5 de 23 a 27) y felicidad (Lyubomirsky de 4 a 4,5) de los pacientes a los treinta días tras el alta hospitalaria. CONCLUSIONS: Los pacientes ingresados por COVID-19 e incluidos en el programa de rehabilitación respiratoria domiciliaria mediante telerehabilitación mejoran de forma significativa su capacidad funcional, calidad de vida, salud mental y felicidad durante su seguimiento.

Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects.

Non-syndromic hearing impairment (NSHI) is a very heterogeneous genetic condition, involving over 130 genes. Mutations in GJB2, encoding connexin-26, are a major cause of NSHI (the DFNB1 type), but few other genes have significant epidemiological contributions. Mutations in the STRC gene result in the DFNB16 type of autosomal recessive NSHI, a common cause of moderate hearing loss. STRC is located in a tandem duplicated region that includes the STRCP1 pseudogene, and so it is prone to rearrangements causing structural variations. Firstly, we screened a cohort of 122 Spanish familial cases of non-DFNB1 NSHI with at least two affected siblings and unaffected parents, and with different degrees of hearing loss (mild to profound). Secondly, we screened a cohort of 64 Spanish sporadic non-DFNB1 cases, and a cohort of 35 Argentinean non-DFNB1 cases, all of them with moderate hearing loss. Amplification of marker D15S784, massively parallel DNA sequencing, multiplex ligation-dependent probe amplification and long-range gene-specific PCR followed by Sanger sequencing were used to search and confirm single-nucleotide variants (SNVs) and deletions involving STRC. Causative variants were found in 13 Spanish familial cases (10.7%), 5 Spanish simplex cases (7.8%) and 2 Argentinean cases (5.7%). In all, 34 deleted alleles and 6 SNVs, 5 of which are novel. All affected subjects had moderate hearing impairment. Our results further support this strong genotype-phenotype correlation and highlight the significant contribution of STRC mutations to moderate NSHI in the Spanish population.

Clinical Outcomes of Patients with Chronic Neuropathic Form of Gaucher Disease in the Spanish Real-World Setting: A Retrospective Study.

This was a retrospective, multicenter study that aimed to report the characteristics of type 3 Gaucher disease (GD3) patients in Spain, including the genotype, phenotype, therapeutic options, and treatment responses. A total of 19 patients with GD3 from 10 Spanish hospitals were enrolled in the study (14 men, 5 women). The median age at disease onset and diagnosis was 1 and 1.2 years, respectively, and the mean age at follow-up completion was 12.37 years (range: 1-25 years). Most patients exhibited splenomegaly (18/19) and hepatomegaly (17/19) at the time of diagnosis. The most frequent neurological abnormalities at onset were psychomotor retardation (14/19) and extrinsic muscle disorders (11/19), including oculomotor apraxia, supranuclear palsy, and strabismus. The L444P (c.1448T>C) allele was predominant, with the L444P (c.1448T>C) homozygous genotype mainly associated with visceral manifestations like hepatosplenomegaly, anemia, and thrombocytopenia. All patients received enzyme replacement therapy (ERT); other treatments included miglustat and the chaperone (ambroxol). Visceral manifestations, including hepatosplenomegaly and hematological and bone manifestations, were mostly controlled with ERT, except for kyphosis. The data from this study may help to increase the evidence base on this rare disease and contribute to improving the clinical management of GD3 patients.

Genotyping of the rs1800440 Polymorphism in CYP1B1 Gene and the rs9258883 Polymorphism in HLA-B Gene in a Spanish Cohort of 223 Patients with Frontal Fibrosing Alopecia.

The pathogenesis of frontal fibrosing alopecia has been linked to specific genetic variants. CYP1B1 codes for a component of the cytochrome p450 machinery that is involved in the metabolism of xenobiotic oestrogens. The study of the prevalence of polymorphisms in this gene may help to understand their role in the development of frontal fibrosing alopecia. The aim of this study is to describe the frequency of genetic variations in the alleles HLA-B*07:02 and CYP1B1 in patients with frontal fibrosing alopecia. A cross-sectional study was designed to evaluate blood samples from patients with frontal fibrosing alopecia who attended the Dermatology Department at University Hospital Ramón y Cajal (Madrid, Spain), in search of the polymorphisms rs9258883 and rs1800440 in the alleles HLA-B*07:02 and CYP1B1, respectively. A total of 223 patients were included in the study. Among the 83.8% of patients who carried the rs9258883 polymorphism in HLA-B*07:02, 58.7% were heterozygous for this variant and it was not present in 14.8% of the cases. The majority of patients with frontal fibrosing alopecia lacked the protective rs1800440 polymorphism in CYP1B1 (75.2%). This suggests a relevant role of this variant in development of frontal fibrosing alopecia. The genetic approach to this condition might influence patient prognosis and therapy options.

Sesamoidectomía peroneal por necrosis séptica

Introducción: Los sesamoideos del hallux son huesos constantes de pequeño tamaño y lentiformes. Se localizan en la región plantar de la cabeza del primer metatarsiano dentro de la cápsula de la primera articulación metatarsofalángica. El diagnóstico diferencial de metatarsalgia sobre el primer radio del pie, sin antecedente traumático, incluye patologías referidas a los sesamoideos y otras. Entre las primeras se encuentran principalmente la sesamoiditis, las fracturas de estrés y la necrosis avascular de los sesamoideos. Objetivo: Presentar un caso de sesamoiditis y su evolución después del tratamiento quirúrgico. Presentación del caso: Mujer de 25 años con un cuadro de fractura por estrés del sesamoideo peroneal. Tras infiltración seriada con corticoesteroides, desencadenó una necrosis séptica del sesamoideo. Se determinó realizar una sesamoidectomía por abordaje plantar. Conclusiones: La sesamoidectomía resulta una opción quirúrgica en procesos degenerativos de los sesamoideos, cuando los tratamientos conservadores son insuficientes. El abordaje plantar se considera adecuado para la extirpación del sesamoideo peroneal. Esta técnica requiere un adecuado seguimiento posoperatorio para optimizar la cicatrización plantar.

Introduction: The hallux sesamoid are constant bones of small size and lentiform. They are located in the plantar region of the first metatarsal head within the capsule of the first metatarsophalangeal joint. The differential diagnosis of metatarsalgia over the first radius of the foot, without traumatic history, includes pathologies related to the sesamoids and others. Among the former are mainly sesamoiditis, stress fractures and avascular necrosis of the sesamoids. Objective: To report a case of sesamoiditis and its evolution after surgical treatment. Case report: This the case of a 25-year-old woman with a stress fracture of the fibular sesamoid. After serial infiltration with corticosteroids, it triggered a septic sesamoid necrosis, it was decided to perform a sesamoidectomy by plantar approach. Conclusions: Sesamoidectomy is a surgical option in degenerative processes of the sesamoids, when conservative treatments are insufficient. The plantar approach is considered adequate for removal of the fibular sesamoid. This technique requires adequate postoperative follow-up to optimize plantar healing.

Intention to use mobile payment by early adopters from mobile phone user data.

The data comes from an empirical study conducted to determine the intention to use mobile devices as a means of payment. The data collection was conducted on a total of 463 students at a university, with 425 valid cases. These students were chosen because of their greater affinity with mobile devices, making them digital natives. The questionnaire was developed using scales recognized in the literature on aspects such as intention to use, learning costs or perceived functional value. The reliability and validity of all constructs showed that the questionnaire was proper for measurement. Data analysis was applied l to examine the validity of scales. But, what makes this data really interesting and singular is the collection of data in 2013 (265 respondents) and 2016 (160 respondents). This allows cross-sectional and longitudinal analyses to check the evolution of respondents' perceptions of mobile payments. Results imply that the data is suitable for conducting replication studies.

Primer design for the amplification of the ammonium transporter genes from the uncultured haptophyte algal species symbiotic with the marine nitrogen-fixing cyanobacterium UCYN-A1.

The multiple symbiotic partnerships between closely related species of the haptophyte algae Braarudosphaera bigelowii and the nitrogen-fixing cyanobacteria Candidatus Atelocyanobacterium thalassa (UCYN-A) contribute importantly to the nitrogen and carbon cycles in vast areas of the ocean. The diversity of the eukaryotic 18S rDNA phylogenetic gene marker has helped to identify some of these symbiotic haptophyte species, yet we still lack a genetic marker to assess its diversity at a finer scale. One of such genes is the ammonium transporter (amt) gene, which encodes the protein that might be involved in the uptake of ammonium from UCYN-A in these symbiotic haptophytes. Here, we designed three specific PCR primer sets targeting the amt gene of the haptophyte species (A1-Host) symbiotic with the open ocean UCYN-A1 sublineage, and tested them in samples collected from open ocean and near-shore environments. Regardless of the primer pair used at Station ALOHA, which is where UCYN-A1 is the pre-dominant UCYN-A sublineage, the most abundant amt amplicon sequence variant (ASV) was taxonomically classified as A1-Host. In addition, two out of the three PCR primer sets revealed the existence of closely-related divergent haptophyte amt ASVs (>95% nucleotide identity). These divergent amt ASVs had higher relative abundances than the haptophyte typically associated with UCYN-A1 in the Bering Sea, or co-occurred with the previously identified A1-Host in the Coral Sea, suggesting the presence of new diversity of closely-related A1-Hosts in polar and temperate waters. Therefore, our study reveals an overlooked diversity of haptophytes species with distinct biogeographic distributions partnering with UCYN-A, and provides new primers that will help to gain new knowledge of the UCYN-A/haptophyte symbiosis.

Non-cyanobacterial diazotrophs: global diversity, distribution, ecophysiology, and activity in marine waters.

Biological dinitrogen (N2) fixation supplies nitrogen to the oceans, supporting primary productivity, and is carried out by some bacteria and archaea referred to as diazotrophs. Cyanobacteria are conventionally considered to be the major contributors to marine N2 fixation, but non-cyanobacterial diazotrophs (NCDs) have been shown to be distributed throughout ocean ecosystems. However, the biogeochemical significance of marine NCDs has not been demonstrated. This review synthesizes multiple datasets, drawing from cultivation-independent molecular techniques and data from extensive oceanic expeditions, to provide a comprehensive view into the diversity, biogeography, ecophysiology, and activity of marine NCDs. A NCD nifH gene catalog was compiled containing sequences from both PCR-based and PCR-free methods, identifying taxa for future studies. NCD abundances from a novel database of NCD nifH-based abundances were colocalized with environmental data, unveiling distinct distributions and environmental drivers of individual taxa. Mechanisms that NCDs may use to fuel and regulate N2 fixation in response to oxygen and fixed nitrogen availability are discussed, based on a metabolic analysis of recently available Tara Oceans expedition data. The integration of multiple datasets provides a new perspective that enhances understanding of the biology, ecology, and biogeography of marine NCDs and provides tools and directions for future research.

Diazotrophs are overlooked contributors to carbon and nitrogen export to the deep ocean.

Diazotrophs are widespread microorganisms that alleviate nitrogen limitation in 60% of our oceans, thereby regulating marine productivity. Yet, the group-specific contribution of diazotrophs to organic matter export has not been quantified, which so far has impeded an accurate assessment of their impact on the biological carbon pump. Here, we examine the fate of five groups of globally-distributed diazotrophs by using an original combination of mesopelagic particle sampling devices across the subtropical South Pacific Ocean. We demonstrate that cyanobacterial and non-cyanobacterial diazotrophs are exported down to 1000 m depth. Surprisingly, group-specific export turnover rates point to a more efficient export of small unicellular cyanobacterial diazotrophs (UCYN) relative to the larger and filamentous Trichodesmium. Phycoerythrin-containing UCYN-B and UCYN-C-like cells were recurrently found embedded in large (>50 µm) organic aggregates or organized into clusters of tens to hundreds of cells linked by an extracellular matrix, presumably facilitating their export. Beyond the South Pacific, our data are supported by analysis of the Tara Oceans metagenomes collected in other ocean basins, extending the scope of our results globally. We show that, when diazotrophs are found in the euphotic zone, they are also systematically present in mesopelagic waters, suggesting their transport to the deep ocean. We thus conclude that diazotrophs are a significant part of the carbon sequestered in the deep ocean and, therefore, they need to be accounted in regional and global estimates of export.

Tecnologías de la información y comunicación, ansiedad y consumo de drogas lícitas en adolescentes / Information and communication technologies, anxiety and legal drug use in adolescents / Tecnologias de informação e comunicação, ansiedade e uso de drogas lícitas em adolescentes

Objetivo: identificar la relación entre el uso de las tecnologías de la información y comunicación (TIC ́s) y la ansiedad, el consumo de alcohol y tabaco en adolescentes de secundaria de Puebla, México.Método: estudio descriptivo correlacional, realizado con 301 adolescentes de una escuela pública en 2018. Se aplicó el Cuestionario de Detección de Nuevas Adicciones y Escala de Ansiedad de Hamilton. Para análisis estadístico, el coeficiente de KolmogorovSmirnov e Ude Mann Whitney, correlación de Spearman y regresión lineal múltiple. Resultados: el uso medio de las TIC ́s fue de 84,36 (DE = 15,1). Internet (M = 16.72, SD = 4.6) y teléfonos celulares (M = 15.52, SD = 5.0) fueron los más utilizados. El uso de las TIC ́s y la ansiedad fueron estadísticamente significativos (F=21.719, p=.001), donde internet y la televisión predijeron la ansiedad. Sobre el uso de TIC ́s y consumo de alcohol (F = 3.745, p =.001) indica que lo que predice esta condición es el uso de celulares. En el caso de las TIC ́s con el consumo de tabaco no hubo significación estadística. Conclusión: existe relación con el uso de las TIC ́s, la ansiedad y el consumo de alcohol en estudiantes de secundaria del estado de Puebla.

Objective: to identify the relationship between the use of information and communication technologies (ICTs) and anxiety, alcohol and tobacco consumption in highschool adolescents from Puebla, Mexico. Method: descriptive correlational study, carried out with 301 adolescents from a public school in 2018. The New Addictions Detection Questionnaire and Hamilton Anxiety Scale were applied. For statistical analysis, the Kolmogorov Smirnov coefficient and Mann Whitney U, Spearman correlation and multiple linear regression. Results: the mean use of ICTs was 84.36 (SD = 15.1). Internet (M = 16.72, SD = 4.6) and cell phones (M = 15.52, SD = 5.0) were the most used. The useof ICTs and anxiety were statistically significant (F=21.719, p=.001), where the Internet and television predicted anxiety. About the use of ICTs and alcohol consumption (F = 3.745, p =.001) indicates that what this condition predicts is the use of cell phones. In the case of ICTs with tobacco use, there was no statistical significance. Conclusion: there is a relationship with the use of ICTs, anxiety and alcohol consumption in high school students in the state of Puebla.

Objetivo:identificar a relação entre o uso de tecnologias de informação e comunicação (TIC) e ansiedade, consumo de álcool e tabaco em adolescentes do ensino médio de Puebla, México. Método: estudo descritivo correlacional, realizado com 301 adolescentes de uma escola pública no ano de 2018. Foram aplicados o New Addictions Detection Questionnaire e a Hamilton Anxiety Scale. Para análise estatística, o coeficiente de Kolmogorov Smirnov e Mann Whitney U, correlação de Spearman e regressão linear múltipla. Resultados: o uso médio de TIC foi de 84.36 (DP= 15.1). A internet (M = 16.72, DP = 4.6) e o celular (M= 15.52, DP= 5.0) foram os mais utilizados. O uso de TIC e ansiedade foi estatisticamente significativo (F = 21.719, p =.001), onde a internet e a televisão predizem a ansiedade. Sobre o uso de TIC e consumo de álcool (F = 3.745, p =.001) indica que quem prediz essa condição é o uso de celulares. No caso das TIC com uso de tabaco, não houve significância estatística. Conclusão: existe uma relação com o uso de TIC, ansiedade e consumo de álcool em estudantes do ensino médio no estado de Puebla.