Characterising the genetic architecture of changes in adiposity during adulthood using electronic health records.

Obesity is a heritable disease, characterised by excess adiposity that is measured by body mass index (BMI). While over 1,000 genetic loci are associated with BMI, less is known about the genetic contribution to adiposity trajectories over adulthood. We derive adiposity-change phenotypes from 24.5 million primary-care health records in over 740,000 individuals in the UK Biobank, Million Veteran Program USA, and Estonian Biobank, to discover and validate the genetic architecture of adiposity trajectories. Using multiple BMI measurements over time increases power to identify genetic factors affecting baseline BMI by 14%. In the largest reported genome-wide study of adiposity-change in adulthood, we identify novel associations with BMI-change at six independent loci, including rs429358 (APOE missense variant). The SNP-based heritability of BMI-change (1.98%) is 9-fold lower than that of BMI. The modest genetic correlation between BMI-change and BMI (45.2%) indicates that genetic studies of longitudinal trajectories could uncover novel biology of quantitative traits in adulthood.

Updated HIV-1 Consensus Sequences Change but Stay Within Similar Distance From Worldwide Samples.

HIV consensus sequences are used in various bioinformatic, evolutionary, and vaccine related research. Since the previous HIV-1 subtype and CRF consensus sequences were constructed in 2002, the number of publicly available HIV-1 sequences have grown exponentially, especially from non-EU and US countries. Here, we reconstruct 90 new HIV-1 subtype and CRF consensus sequences from 3,470 high-quality, representative, full genome sequences in the LANL HIV database. While subtypes and CRFs are unevenly spread across the world, in total 89 countries were represented. For consensus sequences that were based on at least 20 genomes, we found that on average 2.3% (range 0.8-10%) of the consensus genome site states changed from 2002 to 2021, of which about half were nucleotide state differences and the rest insertions and deletions. Interestingly, the 2021 consensus sequences were shorter than in 2002, and compared to 4,674 HIV-1 worldwide genome sequences, the 2021 consensuses were somewhat closer to the worldwide genome sequences, i.e., showing on average fewer nucleotide state differences. Some subtypes/CRFs have had limited geographical spread, and thus sampling of subtypes/CRFs is uneven, at least in part, due to the epidemiological dynamics. Thus, taken as a whole, the 2021 consensus sequences likely are good representations of the typical subtype/CRF genome nucleotide states. The new consensus sequences are available at the LANL HIV database.

Características epidemiológicas de la tuberculosis en un hospital de referencia / Determinants of Smoking in Pregnant Women treated in Public Institutions in the Province of Tucumán, Argentina

Introducción: En la actualidad, la tuberculosis es la novena causa de muerte y la primera por enfermedades infecciosas. Según estimaciones hay 10 millones de nuevos casos de enfermos por año en todo el mundo con más de un millón de muertes anuales. El objetivo del presente trabajo es caracterizar los pacientes diagnosticados de tuberculosis y tratados en el Hospital Transito Cáceres de Allende de la Ciudad de Córdoba. Material y métodos: Se realizó un estudio retrospectivo, observacional, descriptivo, de corte transversal. Resultados: Se incluyeron 69 pacientes, 57,9% fueron hombres. El grupo etario más afectado fue entre los 26 y 65 años. El 35% no tenía trabajo, y de los que si tenían, una gran parte no tenía estabilidad laboral. Ocho pacientes tenían algún grado de inmunocompromiso, presentando solo 1 infección por HIV. No hubo casos de pacientes con resistencia a drogas antituberculosas. Conclusiones: Las características epidemiológicas de nuestros pacientes son similares a otras publicaciones de la región. Conocerlas nos permite tomar decisiones de manejo diario, tanto en diagnóstico y tratamiento, como en la prevención y control de foco para limitar la propagación de la misma.

Epidemiological Characteristics of Tuberculosis in a Reference Hospital

Introduction: At present, tuberculosis is the ninth cause of death, the first from infectious diseases. According to some estimates, there are 10 million new cases of ill people with tuberculosis per year throughout the world, with more than one million annual deaths. The objective of this study was to characterize patients diagnosed with tuberculosis who were treated in the Hospital Transito Cáceres de Allende of the city of Córdoba. Materials and Methods: We conducted a retrospective, observational, descriptive, cross-sectional study. Results: 57.9% of the 69 patients included in the study were male. The most affected age group was between 26 and 65 years. 35% did not have a job, and a large part of those who were employed did not have job stability. Eight patients were partially immunocompromised and there was only 1 case of HIV infection. There were no cases of antituberculous drug-resistant patients. Conclusions: The epidemiological characteristics of our patients are similar to other publications of the area. Knowing about them allows us to make decisions regarding daily management, both in terms of diagnosis and treatment, and also prevention and outbreakcontrol, in order to limit disease propagation.

Trastornos respiratorios del sueño: más allá del índice apneas e hipopneas / Sleep-Disordered Breathing: Looking Beyond the Apnea/Hypopnea Index

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Effect of peristaltic-like movement on bioengineered intestinal tube.

The intestine is a highly heterogeneous hollow organ with biological, mechanical and chemical differences between lumen and wall. A functional human intestine model able to recreate the in vivo dynamic nature as well as the native tissue morphology is demanded for disease research and â€‹drug discovery. Here, we present a system, which combines an engineered three-dimensional (3D) tubular-shaped intestine model (3D In-tube) with a custom-made microbioreactor to impart the key aspects of the in vivo microenvironment of the human intestine, mimicking the rhythmic peristaltic movement. We adapted a previously established bottom-up tissue engineering approach, to produce the 3D tubular-shaped lamina propria and designed a glass microbioreactor to induce the air-liquid interface â€‹condition and peristaltic-like motion. Our results demonstrate the production of a villi-like protrusion and a correct spatial differentiation of the intestinal epithelial cells in enterocyte-like as well as mucus-producing-like cells on the lumen side of the 3D In-tube. This dynamic platform offers a proof-of-concept model of the human intestine.

Amiloidosis pulmonar alveolo septal calcificada como manifestación inicial de mieloma múltiple / Calcified Alveolar Septal Pulmonary Amyloidosis as an Initial Manifestation of Multiple Myeloma

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The phylogeny of extant starfish (Asteroidea: Echinodermata) including Xyloplax, based on comparative transcriptomics.

Multi-locus phylogenetic studies of echinoderms based on Sanger and RNA-seq technologies and the fossil record have provided evidence for the Asterozoa-Echinozoa hypothesis. This hypothesis posits a sister relationship between asterozoan classes (Asteroidea and Ophiuroidea) and a similar relationship between echinozoan classes (Echinoidea and Holothuroidea). Despite this consensus around Asterozoa-Echinozoa, phylogenetic relationships within the class Asteroidea (sea stars or starfish) have been controversial for over a century. Open questions include relationships within asteroids and the status of the enigmatic taxon Xyloplax. Xyloplax is thought by some to represent a newly discovered sixth class of echinoderms - and by others to be an asteroid. To address these questions, we applied a novel workflow to a large RNA-seq dataset that encompassed a broad taxonomic and genomic sample. This study included 15 species sampled from all extant orders and 13 families, plus four ophiuroid species as an outgroup. To expand the taxonomic coverage, the study also incorporated five previously published transcriptomes and one previously published expressed sequence tags (EST) dataset. We developed and applied methods that used a range of alignment parameters with increasing permissiveness in terms of gap characters present within an alignment. This procedure facilitated the selection of phylogenomic data subsets from large amounts of transcriptome data. The results included 19 nested data subsets that ranged from 37 to 4,281loci. Tree searches on all data subsets reconstructed Xyloplax as a velatid asteroid rather than a new class. This result implies that asteroid morphology remains labile well beyond the establishment of the body plan of the group. In the phylogenetic tree with the highest average asteroid nodal support several monophyletic groups were recovered. In this tree, Forcipulatida and Velatida are monophyletic and form a clade that includes Brisingida as sister to Forcipulatida. Xyloplax is consistently recovered as sister to Pteraster. Paxillosida and Spinulosida are each monophyletic, with Notomyotida as sister to the Paxillosida. Valvatida is recovered as paraphyletic. The results from other data subsets are largely consistent with these results. Our results support the hypothesis that the earliest divergence event among extant asteroids separated Velatida and Forcipulatacea from Valvatacea and Spinulosida.

EchinoDB, an application for comparative transcriptomics of deeply-sampled clades of echinoderms.

BACKGROUND: One of our goals for the echinoderm tree of life project (http://echinotol.org) is to identify orthologs suitable for phylogenetic analysis from next-generation transcriptome data. The current dataset is the largest assembled for echinoderm phylogeny and transcriptomics. We used RNA-Seq to profile adult tissues from 42 echinoderm specimens from 24 orders and 37 families. In order to achieve sampling members of clades that span key evolutionary divergence, many of our exemplars were collected from deep and polar seas. DESCRIPTION: A small fraction of the transcriptome data we produced is being used for phylogenetic reconstruction. Thus to make a larger dataset available to researchers with a wide variety of interests, we made a web-based application, EchinoDB (http://echinodb.uncc.edu). EchinoDB is a repository of orthologous transcripts from echinoderms that is searchable via keywords and sequence similarity. CONCLUSIONS: From transcripts we identified 749,397 clusters of orthologous loci. We have developed the information technology to manage and search the loci their annotations with respect to the Sea Urchin (Strongylocentrotus purpuratus) genome. Several users have already taken advantage of these data for spin-off projects in developmental biology, gene family studies, and neuroscience. We hope others will search EchinoDB to discover datasets relevant to a variety of additional questions in comparative biology.

Association between RAD 51 rs1801320 and susceptibility to glioblastoma.

Glioblastoma is the most common and aggressive malignant primary brain tumor. Despite decades of research and the advent of new therapies, patients with glioblastoma continue to have a very poor prognosis. Radiation therapy has a major role as adjuvant treatment for glioblastoma following surgical resection. Many studies have shown that polymorphisms of genes involved in pathways of DNA repair may affect the sensitivity of the cells to treatment. Although the role of these polymorphisms has been investigated in relation to response to radiotherapy, their role as predisposing factors to glioblastoma has not been clarified yet. In the present study, we evaluated the association between polymorphisms in DNA repair genes, namely: XRCC1 rs25487, XRCC3 rs861539 and RAD51 rs1801320, with the susceptibility to develop glioblastoma. Eighty-five glioblastoma patients and 70 matched controls were recruited for this study. Data from the 1000 Genomes Project (98 Tuscans) were also downloaded and used for the association analysis. Subjects carrying RAD51 rs1801320 GC genotype showed an increased risk of glioblastoma (GC vs GG, χ(2) = 10.75; OR 3.0087; p = 0.0010). The C allele was also significantly associated to glioblastoma (χ(2) = 8.66; OR 2.5674; p = 0.0032). Moreover, RAD51 rs1801320 C allele increased the risk to develop glioblastoma also when combined to XRCC1 rs25487 G allele and XRCC3 rs861539 C allele (χ(2) = 6.558; p = 0.0053).

Phylotranscriptomic analysis uncovers a wealth of tissue inhibitor of metalloproteinases variants in echinoderms.

Tissue inhibitors of metalloproteinases (TIMPs) help regulate the extracellular matrix (ECM) in animals, mostly by inhibiting matrix metalloproteinases (MMPs). They are important activators of mutable collagenous tissue (MCT), which have been extensively studied in echinoderms, and the four TIMP copies in humans have been studied for their role in cancer. To understand the evolution of TIMPs, we combined 405 TIMPs from an echinoderm transcriptome dataset built from 41 specimens representing all five classes of echinoderms with variants from protostomes and chordates. We used multiple sequence alignment with various stringencies of alignment quality to cull highly divergent sequences and then conducted phylogenetic analyses using both nucleotide and amino acid sequences. Phylogenetic hypotheses consistently recovered TIMPs as diversifying in the ancestral deuterostome and these early lineages continuing to diversify in echinoderms. The four vertebrate TIMPs diversified from a single copy in the ancestral chordate, all other copies being lost. Consistent with greater MCT needs owing to body wall liquefaction, evisceration, autotomy and reproduction by fission, holothuroids had significantly more TIMPs and higher read depths per contig. Ten cysteine residues, an HPQ binding site and several other residues were conserved in at least 70% of all TIMPs. The conservation of binding sites and the placement of echinoderm TIMPs involved in MCT modification suggest that ECM regulation remains the primary function of TIMP genes, although within this role there are a large number of specialized copies.

Antinociceptive activity of Syzygium cumini leaves ethanol extract on orofacial nociception protocols in rodents.

CONTEXT: Syzygium cumini (L.) Skeels (Myrtaceae) is a tree with dark purple fruits, popularly known as "jambolão" or "jambolan". In folk medicine, this plant is used for the treatment of diabetes and inflammatory conditions. OBJECTIVE: We investigated the antinociceptive effect of ethanol extract (EE) from S. cumini leaves on orofacial nociception. MATERIAL AND METHODS: The antinociceptive effects of the EE obtained from the leaves of S. cumini were evaluated in mice using formalin- and glutamate-induced orofacial nociception. RESULTS: ESI-MS/MS analyses demonstrated that major constituents in the analyzed samples coincided with the mass of the phenolic acids and flavonoids. In pharmacological approach, pre-treatment with EE (100, 200, or 400 mg/kg, p.o.) significantly reduced (p<0.05 or p<0.01) the percentage of paw licks time during phase 2 (43.2, 47.1, and 57.4%, respectively) of a formalin pain test when compared to control group animals. This effect was prevented by pretreatment with glibenclamide and N(G)-nitro-l-arginine (l-NOARG). The extract, all doses, also caused a marked inhibition (p<0.01 or p<0.001) of glutamate-induced orofacial nociception (38.8, 51.7, and 54.7%) when compared with the control group. No effect was observed with the rota-rod model. CONCLUSIONS: We can suggest that the antinociceptive effect of the EE is mediated by peripheral mechanisms, possibly involving KATP channels and the nitric oxide pathways. These effects appear to be related to the presence of flavonoids compounds, such as quercetin.

[Quality of life in patients with COPD and long term oxygen therapy]. / Calidad de vida en pacientes EPOC con oxigeno terapia domiciliaria.

UNLABELLED: Chronic Obstructive Pulmonary Disease (COPD) leads to disability, being long-term oxygen therapy (LTOT) fundamental in final stages. It is important to assess its impact on patient's daily life. OBJECTIVES: To describe factors that determine the quality of life in COPD patients with LTOT, taking into account demographic variables: age and sex, Physiological: POST BD FEV1, BMI, hours of use of OCD and SpO2, Psychological: Dyspnea: St. George's questionnaire (SGRQ ) and Hospital Anxiety and depression Scale. MATERIAL AND METHODS: Observational, cross. 26 patients were included without associated comorbidities. RESULTS: 73.07% male, age: 61.73 ± 1.48 years, the average hours of use of LTOT was equal to 18.88 ± 0.77 hours, the average post-BD FEV 1 was 34.23 ± 2.63%. More anxiety and depression were observed among females. Age had an inverse correlation with the lung function but it had positive lineal correlation with the perception of dyspnea. There was less perception of dyspnea with more hours of use of LTOT. Statistical significance was achieved for the perception of dyspnea and post BD FEV1 as well as with perception of dyspnea and anxiety /depression (p< 0.05). CONCLUSIONS: Anxiety and depression are highly prevalent symptoms in patients with severe COPD that also use LTOT, being higher in women. We stress the importance of using validated scales of quality of life and mental health status, to assess the overall impact of disease and optimize the treatment.

Effects of toluidine blue-mediated photodynamic therapy on periopathogens and periodontal biofilm: in vitro evaluation.

Photodynamic therapy (PDT) is a selective modality of killing targeted cells, mostly known for its application in neoplasms. PDT can be considered to be an alternative method for the elimination of periodontal bacteria from the pocket without harms for the resident tissues. Therefore, PDT may replace systemic antibiotics and enhance the effect of mechanical treatments of periodontal defects. This effort focused on the in vitro sensitization of periopathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia ) Toluidine Blue mediated and on the use of a Diode laser emitting source. The objective of this research was to evaluate the bactericidal in vitro effect of laser diodes 830 nm (as the light source) after photosensitization with Toluidine Blue (TBO) on the following periopathogenic bacteria: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia. After evaluating the effect on the single bacterial strain, the ability of Diode Laser to disrupt the structure of biofilms produced by A. actinomycetemcomitans after photosensitization with TBO was also analyzed. The study suggests that the association of TBO and diode laser light 830 nm is effective for the killing of bacteria strains and determines the photoinactivation of Aggregatibacter biofilms. In summary, photodynamic therapy has effectively shown its capabilities and, therefore, it can be considered a valid alternative approach to antimicrobial therapy of periodontitis.

Inhibition of HSV-1 replication by laser diode-irradiation: possible mechanism of action.

Herpes labialis are the most frequent clinical manifestations of HSV-1 infection. Epithelial cells are able to respond to HSV-1 presence inducing the expression of IL-6, IL-1, TNF-α and IL-8. These proinflammatory cytokines have a function in the acute-phase response mediation, chemotaxis, inflammatory cell activation and antigen-presenting cells. In the human epithelial cell models, it has been demonstrated that, after an early induction of proinflammatory host response, HSV-1 down-modulates the proinflammatory cytokine production through the accumulation of two viral proteins, ICP4 and ICP27, whose transcription is induced by tegument protein VP16. These viral proteins, through the decreasing of stabilizing the mRNAs of proinflammatory genes, delay cytokine production to an extent that allows the virus to replicate. Moreover, viral transactivating proteins, ICP-0 and VP-16 induce IL-10 expression. The conventional treatment of herpes labialis involves the topical and systemic use of antiviral drugs but it is necessary to find new therapies that can act in a selective and non-cytotoxic manner in viral infection. Laser diode therapy has been considered as a non-invasive alternative treatment to the conventional treatment of herpes labialis in pain therapy, in modulation of inflammation and in wound healing. This study aims to report a possible mechanism of action of laser diode irradiation in prevention and reduction of severity of labial manifestations of herpes labialis virus. We investigated, in an in vitro model of epithelial cells HaCat, the laser-effect on HSV-1 replication and we evaluated the modulation of expression of certain proinflammatory cytokines (TNF-α, IL-1ß and IL-6), antimicrobial peptide HBD2, chemokine IL-8 and the immunosuppressive cytokine, IL-10. Our results lead us to hypothesize that LD-irradiation acts in the final stage of HSV-1 replication by limiting viral spread from cell to cell and that laser therapy acts also on the host immune response unblocking the suppression of proinflammatory mediators induced by accumulation of progeny virus in infected epithelial cells.

Nuclear and cytoplasmic interaction of pRb2/p130 and ER-beta in MCF-7 breast cancer cells.

Estrogens exhibit important biological functions and influence several pathological processes of hormone-dependent diseases. The biological actions of estrogens require their interaction with two estrogen receptors (ER-alpha and ER-beta), which are ligand-dependent transcription factors. ER-alpha and ER-beta exhibit distinct tissue expression patterns as well as show different patterns of gene regulation. In addition, it has been suggested that ER-beta works as a counter partner of ER-alpha through inhibition of the transactivating functions of ER-alpha. For instance, ER-beta seems to play a different role in breast tumorigenesis than ER-alpha, as ER-beta decreased expression in breast cancer has been correlated with bad prognosis. Biological activities of ER-alpha and ER-beta could be controlled by a number of interacting proteins such as activators/inhibitors, ligand binding and kinases. We have previously reported that pRb2/p130, retinoblastoma related protein, could be involved in the silencing of ER-alpha gene during breast tumorigenesis. Here, we report that ER-beta and pRb2/p130 proteins co-immunoprecipitate in both nucleus and cytoplasm of MCF-7 breast cancer cells. Our hypothesis is that the interaction of pRb2/130 with ER-beta may have a functional significance in regulating ER-beta activity.

Dicationic electrophiles from olefinic amines in superacid.

This paper describes the superacid-catalyzed chemistry of olefinic amines and related compounds. A variety of olefinic amines are found to react with benzene in CF(3)SO(3)H (triflic acid) to give addition products in good yields (75-99%), including the pharmaceutical agents fenpiprane and prozapine. A general mechanism is proposed that invokes the formation of reactive, dicationic electrophiles and the direct observation of a diprotonated species is reported from low-temperature NMR experiments. This chemistry is also used to conveniently prepare functionalized polystyrene beads having pendant amine groups.