Comparison of Sedation and Analgesia Requirements in Patients With SARS-CoV-2 Versus Non-SARS-CoV-2 Acute Respiratory Distress Syndrome on Veno-Venous ECMO.

BACKGROUND: Increased analgosedation requirements have been described in patients with acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO) support due to unique pharmacokinetic challenges. There is a paucity of data comparing sedation requirements in patients on ECMO for ARDS secondary to SARS-CoV-2 versus other etiologies of respiratory failure. OBJECTIVE: To compare sedation and analgesia requirements in adult patients with SARS-CoV-2 versus non-SARS-CoV-2 ARDS requiring veno-venous (VV) ECMO support. METHODS: We performed a retrospective cohort study of adult patients receiving sedation and analgesia on VV-ECMO support. Patients were excluded if cannulated at an outside hospital for greater than 24 hours, expired within 48 hours of ECMO cannulation, or received neuromuscular blocking agents for greater than 7 consecutive days following ECMO cannulation. RESULTS: We evaluated 108 patients on VV-ECMO support, including 44 with non-SARS-CoV-2 ARDS and 64 with SARS-CoV-2 ARDS. The median daily dexmedetomidine requirements were significantly higher in the SARS-CoV-2 cohort (16.7 vs 13.4 mcg/kg/day, P = 0.03), while the median propofol daily requirements were significantly higher in the non-SARS-CoV-2 cohort (40.3 vs 53.5 mg/kg/day, P < 0.01). There was no difference in daily requirements of opioids, benzodiazepines, and ketamine between groups. Use of adjunct agents to facilitate weaning was significantly higher in the SARS-CoV-2 cohort (78.1% vs 43.2%, P < 0.01). CONCLUSION AND RELEVANCE: Patients with ARDS on VV-ECMO support require multiple analgosedative agents with concomitant use of nonparenteral adjunct agents. Further studies are needed to evaluate optimal analgosedation strategies in patients on ECMO support.

Effectiveness of a group intervention using pain neuroscience education and exercise in women with fibromyalgia: a pragmatic controlled study in primary care.

BACKGROUND: Very positive effects have been described in the application of pain neuroscience education (PNE) to chronic pain and migraine. However, there are few data on the applicability of this therapeutic approach in actual clinical practice in a primary care (PC) setting. The aim of this study was to explore the efficacy in fibromyalgia (FM) of an intervention based on PNE and exercise compared to treatment as usual (TAU). METHODS: Pragmatic nonrandomised controlled trial set in 5 healthcare centres and one physiotherapy centre in PC. Fifty-three women with FM (2010 American College of Rheumatology Diagnostic Criteria for Fibromyalgia) were studied, 35 in the intervention group (IG) and 18 in the control group (CG). The women in the IG were interviewed individually and then received 6 weekly sessions plus one review session (1 month later): those in the CG received their TAU. The subject assignation to the CG or the IG was determined according to their availability to attend the sessions. They all filled in several questionnaires (prior to and 1 year after the intervention) to evaluate the impact of FM in their daily lives, catastrophism, anxiety and depression, severity and impact of pain in daily personal performance and functional capacity. RESULTS: The reductions (improvements) in the scores of all tests (baseline-final) were greater in the IG (p < 0.05) when adjusted for age and baseline values, with moderate or high effect size. After 1 year, 20% (CI - 1 to 42%) more women in the IG, compared to the CG, had a FIQ score < 39 (mild functional impairment). 17/38 (49%) women in the IG no longer met FM criteria at the end of follow-up. CONCLUSIONS: An intervention based on PNE and exercise in patients with FM is feasible and seems effective in PC. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov (Trial Registration NCT04539171 ), on 04/09/2020.

Endogenous indole-3-acetamide levels contribute to the crosstalk between auxin and abscisic acid, and trigger plant stress responses in Arabidopsis.

The evolutionary success of plants relies to a large extent on their extraordinary ability to adapt to changes in their environment. These adaptations require that plants balance their growth with their stress responses. Plant hormones are crucial mediators orchestrating the underlying adaptive processes. However, whether and how the growth-related hormone auxin and the stress-related hormones jasmonic acid, salicylic acid, and abscisic acid (ABA) are coordinated remains largely elusive. Here, we analyse the physiological role of AMIDASE 1 (AMI1) in Arabidopsis plant growth and its possible connection to plant adaptations to abiotic stresses. AMI1 contributes to cellular auxin homeostasis by catalysing the conversion of indole-acetamide into the major plant auxin indole-3-acetic acid. Functional impairment of AMI1 increases the plant's stress status rendering mutant plants more susceptible to abiotic stresses. Transcriptomic analysis of ami1 mutants disclosed the reprogramming of a considerable number of stress-related genes, including jasmonic acid and ABA biosynthesis genes. The ami1 mutants exhibit only moderately repressed growth but an enhanced ABA accumulation, which suggests a role for AMI1 in the crosstalk between auxin and ABA. Altogether, our results suggest that AMI1 is involved in coordinating the trade-off between plant growth and stress responses, balancing auxin and ABA homeostasis.

Diagnostic Accuracy of the Rome IV Criteria for the Diagnosis of Functional Gastrointestinal Disorders in Children.

ABSTRACT: The diagnosis of functional gastrointestinal disorders (FGIDs) centers on symptoms-based criteria (Rome criteria). The last edition of the criteria was published in 2016. Still, few data on its validity support its use in children. We conducted a study aimed at determining the diagnostic accuracy of the Rome IV criteria through the application of questionnaires (Questionnaire of Pediatric Gastrointestinal Symptoms-Rome IV QPGS-IV) to diagnose FGIDs in children. We hypothesized that the Rome IV criteria has adequate diagnostic accuracy supporting its use for diagnosing FGIDs in children. METHODS: School children ages 10 to 18 years from Cali (Colombia) completed the Spanish version of the QPGS-IV. Children with FGIDs were matched with a group of children without FGIDs. Both groups had a medical consultation with a blinded experienced pediatric gastroenterologist (criterion standard) who provided his diagnosis. The questionnaire-based diagnoses were compared with the consultation's diagnoses. RESULTS: Of 487 schoolchildren surveyed with the QPGS-IV, 97 (20.8%) had FGIDs. Eighty-nine with FGIDs were matched with 92 children without FGIDs (mean age 13.1 years [±1.3]). We found a higher prevalence of FGIDs during the medical visit than using the self-report QPGS-IV (66.3% vs 49.2%, P = 0.001), mainly in abdominal pain disorders (19.3% vs 10.5%, P = 0.013). The Rome IV diagnostic criteria using the QPGS-IV had a sensitivity of 75% (95% confidence interval, 59-79) and 90% specificity (95% confidence interval, 83-98). Positive predictive value is 85.8%, and negative predictive value is 79.9%. CONCLUSION: Our study suggests that the QPGS-IV has adequate diagnostic accuracy.

Influence of core extension and side chain nature in targeting G-quadruplex structures with perylene monoimide derivatives.

A structure-activity relationship (SAR) study in terms of G-quadruplex binding ability and antiproliferative activity of six fluorescent perylenemonoimide (PMIs) derivatives is reported. A positive charge seems to be the key to target G4. This study also reveals the importance of the element substitution in the potential biological activity of PMIs, being the polyethylene glycol (PEG) chains in the peri position responsible for their antiproliferative activity. Among them, the cationic PMI6 with two PEG chains is the most promising compound since its fluorescence is enhanced in the presence of G-quadruplex structures. Moreover, PMI6 binds to the human telomeric G-quadruplex hTelo with high affinity and displays a high antiproliferative potential towards HeLa (cervical adenocarcinoma), A549 (lung adenocarcinoma) and A2780 (ovarian adenocarcinoma) cells. Its fate can be followed inside cells thanks to its fluorescent properties: the compound is found to accumulate in the mitochondria.

Accumulation of the Auxin Precursor Indole-3-Acetamide Curtails Growth through the Repression of Ribosome-Biogenesis and Development-Related Transcriptional Networks.

The major auxin, indole-3-acetic acid (IAA), is associated with a plethora of growth and developmental processes including embryo development, expansion growth, cambial activity, and the induction of lateral root growth. Accumulation of the auxin precursor indole-3-acetamide (IAM) induces stress related processes by stimulating abscisic acid (ABA) biosynthesis. How IAM signaling is controlled is, at present, unclear. Here, we characterize the ami1rooty double mutant, that we initially generated to study the metabolic and phenotypic consequences of a simultaneous genetic blockade of the indole glucosinolate and IAM pathways in Arabidopsisthaliana. Our mass spectrometric analyses of the mutant revealed that the combination of the two mutations is not sufficient to fully prevent the conversion of IAM to IAA. The detected strong accumulation of IAM was, however, recognized to substantially impair seed development. We further show by genome-wide expression studies that the double mutant is broadly affected in its translational capacity, and that a small number of plant growth regulating transcriptional circuits are repressed by the high IAM content in the seed. In accordance with the previously described growth reduction in response to elevated IAM levels, our data support the hypothesis that IAM is a growth repressing counterpart to IAA.

Health-Related Lifestyles and Cancer-Preventive Behaviors of Medical and Nursing Students and Family Medicine Residents in Relation to the European Code Against Cancer.

Family medicine (FM) residents and medical and nursing students play an important role in the development of preventive and health-promoting activities. The objective was to evaluate the health-related lifestyles and cancer-preventive behaviors of medical and nursing students and FM residents in relation to the European Code Against Cancer (ECAC). This was a descriptive, cross-sectional study performed in Spain. Medical and nursing students and FM residents completed a self-administered questionnaire focused on health-related habits and clinical behaviors related to the ECAC. A total of 740 participants completed the questionnaire. About 12.2% (95% CI [9.8-14.5]) were smokers, and 77.3% (95% CI [74.3-80.3]) sporadically consumed alcohol; 34.2% (95% CI [30.8-37.6]) practiced physical activity 2-3 times a week, and 12.1% (95% CI [9.8-14.5]) were overweight or obese. About 54.2% (95% CI [50.6-57.8]) regularly consumed vegetables. Differences were detected in the completion of screening tests for colorectal cancer (p < 0.001), breast cancer (p = 0.023), cervical cancer (p = 0.006), and prostate-specific antigen determination (p < 0.001) in relation to the participants' academic profiles. Our results reveal heterogeneous practices between the participants in terms of health-related habits. Awareness about the risks of smoking and being overweight were high; however, the perception of the risks associated with solar exposure and alcohol consumption was poor. There was general agreement upon the importance of performing screening tests for breast, cervical, and colorectal cancer, but there were discrepancies related to the need to perform the prostate cancer screening test.

Awareness of the European Code Against Cancer of Family Medicine Residents and Nursing and Medicine Students in Spain.

Health professionals and students in training are key for early diagnosis of cancer. The objective of this study was to evaluate the awareness of Family Medicine (FM) residents and Medicine and Nursing undergraduate students in Spain regarding the European Code Against Cancer (ECAC). This was a descriptive, cross-sectional, and multicenter study. LOCATION: Teaching Units of FM of Cordoba and Ceuta and Schools of Medicine and Nursing of the Universities of Cordoba and Francisco de Vitoria of Madrid (Spain). PARTICIPANTS: residents of FM and Medicine and Nursing undergraduate Spanish students. INTERVENTION: self-administered questionnaire to assess the awareness about the ECAC. A total of 651 subjects participated (52.4% [95% CI 48.5-56.2] Nursing students, 34% [95% CI 30.3-37.6] Medicine students, and 13.6% [95% CI 11.0-16.3] FM residents). Of the total subjects participated, 74.8% were women. Mean age: 22.34 years (standard deviation, 4.68; range, 18-52; 95% CI, 21.98-22.70). A total of 76.8% (95% CI 73.5-80.1) declared to be unaware of the ECAC. Those referring to be aware of the ECAC mainly knew it through degree subjects (7.5% [95% CI 5.5.5-9.6]). Residents of FM (p < 0.001), older participants (p < 0.001), and those belonging to the Teaching Units (p = 0.002) showed a better awareness of the ECAC. Our findings reveal the unawareness on the ECAC in three out of four participants. The access to the advice described in the ECAC through the Medicine and Nursing Schools and FM Teaching Units is poor. The awareness of the ECAC of postgraduate residents is higher than that the awareness of the undergraduate students.

Synthesis of Fluorogenic Arylureas and Amides and Their Interaction with Amines: A Competition between Turn-on Fluorescence and Organic Radicals on the Way to a Smart Label for Fish Freshness.

We describe the synthesis of fluorogenic arylureas and amides and their interaction with primary or secondary amines under air and light in organic-aqueous mixtures to give rise to a new class of persistent organic radicals, described on the basis of their electron paramagnetic resonance (EPR), as well as UV-vis, fluorescence, NMR, and quantum mechanics calculations, and their prospective use as multi-signal reporters in a smart label for fish freshness.

[Effectiveness of pain neuroscience education in patients with fibromyalgia: Structured group intervention in Primary Care]. / Efecto de la educación en neurociencia del dolor en pacientes con fibromialgia: intervención grupal estructurada en atención primaria.

OBJECTIVE: To evaluate the effectiveness of a group intervention in Primary Care in patients with fibromyalgia (FM) based on pain neuroscience education (PNE). DESIGN: Pre-post study. LOCATION: Urban Primary Health Centre in Bilbao. PARTICIPANTS: Patients with FM (2010 American College of Rheumatology Diagnostic Criteria for fibromyalgia), ≥18 years. INTERVENTION: 5 weekly sessions (2hours each), and a reminder session one month later. MAIN MEASUREMENTS: Compliance with FM criteria, assessed using the WPI (Widespread Pain Index, number of pain areas) and the SS (severity of symptoms) questionnaires. An assessment was also made on the impact of FM on functional capacity (FIQ:≥20% and ≥50% reduction in the FIQ total score from baseline to after treatment, and proportion of patients with FIQ<39 at the end of the study). Assessments were made at baseline, one month following the 5th session, and during the 6- and 12-month follow-up. RESULTS: All the study evaluations were completed by 85/98 patients. A statistically significant improvement was observed in the 3 studied categories (WPI, SS, and FIQ) since the first visit, and was maintained until the final visit (12 months later). A total of 45 patients (53%, 95% CI: 42%-63%), more than those at baseline, scored FIQ<39 (no worse than mild functional impairment). One month following the 5th session there were 44 patients (52%, 95% CI: 41%-62%) that no longer met FM criteria and, at the end of follow-up, there were 56 patients (66%, 95% CI: 55%-75%). CONCLUSIONS: An intervention based on PNE has shown to be feasible in Primary Care, with results in the upper range of those published with other treatments for FM.

PRX2 and PRX25, peroxidases regulated by COG1, are involved in seed longevity in Arabidopsis.

Permeability is a crucial trait that affects seed longevity and is regulated by different polymers including proanthocyanidins, suberin, cutin and lignin located in the seed coat. By testing mutants in suberin transport and biosynthesis, we demonstrate the importance of this biopolymer to cope with seed deterioration. Transcriptomic analysis of cog1-2D, a gain-of-function mutant with increased seed longevity, revealed the upregulation of several peroxidase genes. Reverse genetics analysing seed longevity uncovered redundancy within the seed coat peroxidase gene family; however, after controlled deterioration treatment, seeds from the prx2 prx25 double and prx2 prx25 prx71 triple mutant plants presented lower germination than wild-type plants. Transmission electron microscopy analysis of the seed coat of these mutants showed a thinner palisade layer, but no changes were observed in proanthocyanidin accumulation or in the cuticle layer. Spectrophotometric quantification of acetyl bromide-soluble lignin components indicated changes in the amount of total polyphenolics derived from suberin and/or lignin in the mutant seeds. Finally, the increased seed coat permeability to tetrazolium salts observed in the prx2 prx25 and prx2 prx25 prx71 mutant lines suggested that the lower permeability of the seed coats caused by altered polyphenolics is likely to be the main reason explaining their reduced seed longevity.

Structural Characterization of Mono and Dihydroxylated Umbelliferone Derivatives.

Coumarin derivatives are a class of compounds with a pronounced wide range of applications, especially in biological activities, in the medicine, pharmacology, cosmetics, coatings and food industry. Their potential applications are highly dependent on the nature of the substituents attached to their nucleus. These substituents modulate their photochemical and photophysical properties, as well as their interactions in their crystalline form, which largely determines the final field of application. Therefore, in this work a series of mono and dihydroxylated coumarin derivatives with different chemical substituents were synthesized and characterized by UV-Visible spectroscopy, thermal analysis (differential scanning calorimetry (DSC) and TGA), 1H NMR and X-Ray Diffraction to identify limitations and possibilities as a function of the molecular structure for expanding their applications in polymer science.

[Knowledge, conduct and attitude before the European Code against Cancer by health professionals of primary care]. / Conocimiento, conducta y actitud ante el Código europeo contra el cáncer por parte de los profesionales sanitarios de atención primaria.

OBJECTIVE: To decide if Primary Care (PC) professionals know the European Code against Cancer (CECC) and if this relates to practice the recommendations with themselves and with their patients. DESIGN: descriptive, observational study. SETTING: Spanish Health Centers. PARTICIPANTS: Health professionals. INTERVENTIONS: self-administered questionnaire. MAIN MEASUREMENTS: cancer protective and risk factors, screening for colorectal, breast, cervix and prostate cancer, level of knowledge of the ECAC. RESULTS: 1734 participants (10.5%), mean age 47.4 years (SD: 8.6), 71.5% female. 50.0% do not know the CECC; tutors (OR=1.61), assigned to the PAPPS (OR=1.51) and who have been working in AP for more time (OR=2.62) are the ones who know it most. 7.2% smoke and 79.1% drink alcohol. 64.1% presented normal weight and 19% performed physical activity. They avoid exposing themselves to the sun 52.7% and use protectors 53.8%. 85.2% have never had a colorectal screening, 11% never had a cytology, and 12% had a mammogram. There is a relationship between knowing the CECC and smoking (P<.001), overweight/obesity (P=.024), physical activity (P=.003), meat intake (P<.001), mammography (P<.001), cytology (P=.022), PSA (P=.045), as well as the promotion of their advice among patients. CONCLUSIONS: The CECC is unknown by half of the AP professionals. The practice of its recommendations is uneven, with the prevalence of low smoking, and sun protection a little extended behavior. Those who know him are the ones who most practice his recommendations.

Pleural catheter placement and intrapleural fibrinolysis following lung transplantation.

BACKGROUND: This study aimed to investigate the characteristics of lung transplant recipients requiring additional pleural drainage catheters early post-lung transplantation and to determine the safety and efficacy of intrapleural fibrinolytics in these patients. METHODS: A retrospective review of lung transplant recipients at a single center was performed. Patient and transplant characteristics, placement of pleural drainage catheters within 90 days of transplant, and use of intrapleural fibrinolytics were determined. RESULTS: Out of 128 patients who underwent lung transplantation, 54 patients required 86 additional chest tubes, the majority of which were size 14 French or smaller. Pleural effusion was the most common indication for tube placement. Patients who required additional chest tubes were more likely to have chronic obstructive pulmonary disease than those who did not. Use of intrapleural fibrinolytics led to radiographic improvement in 77.8% of patients and was not associated with bleeding, pneumothorax, or mortality within 30 days. CONCLUSIONS: Use of small-bore chest tubes and intrapleural fibrinolytics can be safe and effective in lung transplant recipients with persistent pleural effusions.

Genome-Wide Estimation of the Spontaneous Mutation Rate of Human Adenovirus 5 by High-Fidelity Deep Sequencing.

Rates of spontaneous mutation determine the ability of viruses to evolve, infect new hosts, evade immunity and undergo drug resistance. Contrarily to RNA viruses, few mutation rate estimates have been obtained for DNA viruses, because their high replication fidelity implies that new mutations typically fall below the detection limits of Sanger and standard next-generation sequencing. Here, we have used a recently developed high-fidelity deep sequencing technique (Duplex Sequencing) to score spontaneous mutations in human adenovirus 5 under conditions of minimal selection. Based on >200 single-base spontaneous mutations detected throughout the entire viral genome, we infer an average mutation rate of 1.3 × 10-7 per base per cell infection cycle. This value is similar to those of other, large double-stranded DNA viruses, but an order of magnitude lower than those of single-stranded DNA viruses, consistent with the possible action of post-replicative repair. Although the mutation rate did not vary strongly along the adenovirus genome, we found several sources of mutation rate heterogeneity. First, two regions mapping to transcription units L3 and E1B-IVa2 were significantly depleted for mutations. Second, several point insertions/deletions located within low-complexity sequence contexts appeared recurrently, suggesting mutational hotspots. Third, mutation probability increased at GpC dinucleotides. Our findings suggest that host factors may influence the distribution of spontaneous mutations in human adenoviruses and potentially other nuclear DNA viruses.

Genetic cluster of fragile X syndrome in a Colombian district.

BACKGROUND: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and autism. The reported prevalence of the full mutation (FM) gene FMR1 in the general population is 0.2-0.4 per 1000 males and 0.125-0.4 per 1000 females. Population screening for FMR1 expanded alleles has been performed in newborns and in an adult population. However, it has never been carried out in an entire town. Ricaurte is a Colombian district with 1186 habitants, with a high prevalence of FXS, which was first described by cytogenetic techniques in 1999. METHODS: Using a PCR-based approach, screening for FXS was performed on blood spot samples obtained from 926 (502 males and 424 females) inhabitants from Ricaurte, accounting for 78% of total population. RESULTS: A high prevalence of carriers of the expanded allele was observed in all FXS mutation categories. Using the Bayesian methods the carrier frequency of FM was 48.2 (95% Credibility Region CR: 36.3-61.5) per 1000 males and 20.5 (95% CR:13.5-28.6) per 1000 females; the frequency of premutation carrier was 14.1 (95% RC: 8.0-21.7) per 1000 males (95% RC: 8.0-21.7 per 1000 males) and 35.9 (95% RC: 26.5-46.2) per 1000 for females (95% RC: 26.5-46.2 per 1000 females), and gray zone carrier was 13.4 (95% RC: 7.4-20.7) per 1000 males (95% RC: 7.4-20.7 per 1000 males) and 42.2 (95% RC: 32.2-53.8) per 1000 for females (95% RC: 32.2-53.8 per 1000 females). Differences in carrier frequencies were observed for premutation and FM alleles between natives and non-natives. CONCLUSIONS: This study shows that in Ricaurte the carrier frequencies of FMR1 expanded alleles (premutations and FMs) are higher than those reported in the literature, suggesting that Ricaurte constitutes a genetic cluster of FXS.

Strong Influence of the Ancillary Ligand over the Photodynamic Anticancer Properties of Neutral Biscyclometalated IrIII Complexes Bearing 2-Benzoazole-Phenolates.

In this paper, the synthesis, comprehensive characterization and biological and photocatalytic properties of two series of neutral IrIII biscyclometalated complexes of general formula [Ir(C^N)2 (N^O)], where the N^O ligands are 2-(benzimidazolyl)phenolate-N,O (L1, series a) and 2-(benzothiazolyl)phenolate-N,O (L2, series b), and the C^N ligands are 2-(phenyl)pyridinate or its derivatives, are described,. Complexes of types a and b exhibit dissimilar photophysical and biological properties. In vitro cytotoxicity tests conclusively prove that derivatives of series a are harmless in the dark against SW480 cancer cells (colon adenocarcinoma), but express enhanced cytotoxicity versus the same cells after stimulation with UV or blue light. In contrast, complexes of type b show a very high cytotoxic activity in the dark, but low photosensitizing ability. Thus, the ancillary N^O ligand is the main factor in terms of cytotoxic activity both in the dark and upon irradiation. However, the C^N ligands play a key role regarding cellular uptake. In particular, the complex of formula [Ir(dfppy)2 (L1)] (dfppy=2-(4,6-difluorophenyl)pyridinate) [3 a] has been identified as both an efficient photosensitizer for 1 O2 generation and a potential agent for photodynamic therapy. These capabilities are probably related to a combination of its notable cellular internalization, remarkable photostability, high photoluminescence quantum yield, and long triplet excited-state lifetime. Both types of complexes exhibit notable catalytic activity in the photooxidation of thioanisole and S-containing aminoacids with full selectivity.

Extremely High Mutation Rate of HIV-1 In Vivo.

Rates of spontaneous mutation critically determine the genetic diversity and evolution of RNA viruses. Although these rates have been characterized in vitro and in cell culture models, they have seldom been determined in vivo for human viruses. Here, we use the intrapatient frequency of premature stop codons to quantify the HIV-1 genome-wide rate of spontaneous mutation in DNA sequences from peripheral blood mononuclear cells. This reveals an extremely high mutation rate of (4.1 ± 1.7) × 10-3 per base per cell, the highest reported for any biological entity. Sequencing of plasma-derived sequences yielded a mutation frequency 44 times lower, indicating that a large fraction of viral genomes are lethally mutated and fail to reach plasma. We show that the HIV-1 reverse transcriptase contributes only 2% of mutations, whereas 98% result from editing by host cytidine deaminases of the A3 family. Hypermutated viral sequences are less abundant in patients showing rapid disease progression compared to normal progressors, highlighting the antiviral role of A3 proteins. However, the amount of A3-mediated editing varies broadly, and we find that low-edited sequences are more abundant among rapid progressors, suggesting that suboptimal A3 activity might enhance HIV-1 genetic diversity and pathogenesis.

Cationic Bis(cyclometalated) Ir(III) Complexes with Pyridine-Carbene Ligands. Photophysical Properties and Photocatalytic Hydrogen Production from Water.

Precursors of chelate pyridine-N-heterocyclic carbene (N^C:) ligands with methyl- or benzyl-substituted imidazolylidene fragments were synthesized. They were used to obtain 12 iridium bis-cyclometalated complexes of the type [Ir(C^N)2(N^C:)]+ (C^N = 2-(phenyl)pyridinato-C2,N, ppy, 2-(4,6-difluorophenyl)pyridinato-C2,N, dfppy). The ancillary N^C: ligands contain different structural modifications. The aim of the work was to analyze the effect that changes in the two types of ligands have on the photophysical and electrochemical properties and also on the behavior of these materials as photosensitizers. The X-ray crystal structures of five complexes were determined. The complexes emitted in the blue-green region. It was expected that the frontier orbitals and thus the photophysical and electrochemical properties would be controlled by the main C^N ligands, and it was demonstrated that the effect of the modifications in the N^C: ligand, especially the presence of a nitro group in the pyridine ring or the interruption of conjugation between the two rings, also affected these properties. The quenching with O2 and photostability studies were also performed. Density functional theory calculations were used to explain the behavior of some derivatives. The complexes and other previously reported compounds were employed as photosensitizers (PS) in preliminary studies on the production of H2 from water using [Co(bpy)3]Cl2 (bpy = 2,2'-bipyridine) as catalyst and triethanolamine (TEOA) as the sacrificial reductant. The absence of quenching of the PS with TEOA allowed us to propose an oxidative quenching mechanism.

Role of APOBEC3H in the Viral Control of HIV Elite Controller Patients.

Background APOBEC3H (A3H) gene presents variation at 2 positions (rs139297 and rs79323350) leading to a non-functional protein. So far, there is no information on the role played by A3H in spontaneous control of HIV. The aim of this study was to evaluate the A3H polymorphisms distribution in a well-characterized group of Elite Controller (EC) subjects. Methods We analyzed the genotype distribution of two different SNPs (rs139297 and rs79323350) of A3H in 30 EC patients and compared with 11 non-controller (NC) HIV patients. Genotyping was performed by PCR, cloning and Sanger sequencing. Both polymorphisms were analyzed jointly in order to adequately attribute the active or inactive status of A3H protein. Results EC subjects included in this study were able to maintain a long-term sustained spontaneous HIV-viral control and optimal CD4-T-cell counts; however, haplotypes leading to an active protein were very poorly represented in these patients. We found that the majority of EC subjects (23/30; 77%) presented allelic combinations leading to an inactive A3H protein, a frequency slightly lower than that observed for NC studied patients (10/11; 91%). Conclusions The high prevalence of non-functional protein coding-genotypes in EC subjects seems to indicate that other innate restriction factors different from APOBEC3H could be implicated in the replication control exhibited by these subjects.