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Climate change induced drying and flooding may alter the redox conditions of organic matter decomposition in peat soils. The seasonal and intermittent changes in pore water solutes (NDue to image rights restrictions, multiple line equation(s) cannot be graphically displayed. , Fe2+, SODue to image rights restrictions, multiple line equation(s) cannot be graphically displayed. , H2S, acetate) and dissolved soil gases (CO2, O2, CH4, H2) under natural water table fluctuations were compared to the response under a reinforced drying and flooding in fen peats. Oxygen penetration during dryings led to CO2 and CH4 degassing and to a regeneration of dissolved electron acceptors (NODue to image rights restrictions, multiple line equation(s) cannot be graphically displayed., Fe3+ and SODue to image rights restrictions, multiple line equation(s) cannot be graphically displayed. ). Drying intensity controlled the extent of the electron acceptor regeneration. Iron was rapidly reduced and sulfate pools ∼1mmol L-1 depleted upon rewetting and CH4 did not substantially accumulate until sulfate levels declined to ∼100 µmol l-1. The post-rewetting recovery of soil methane concentrations to levels ∼80 µmol l-1 needed 40-50 days after natural drought. This recovery was prolonged after experimentally reinforced drought. A greater regeneration of electron acceptors during drying was not related to prolonged methanogenesis suppression after rewetting. Peat compaction, solid phase content of reactive iron and total reduced inorganic sulfur and organic matter content controlled oxygen penetration, the regeneration of electron acceptors and the recovery of CH4 production, respectively. Methane production was maintained despite moderate water table decline of 20 cm in denser peats. Flooding led to accumulation of acetate and H2, promoted CH4 production and strengthened the co-occurrence of iron and sulfate reduction and methanogenesis. Mass balances during drying and flooding indicated that an important fraction of the electron flow must have been used for the generation and consumption of electron acceptors in the solid phase or other mechanisms. In contrast to flooding, dry-wet cycles negatively affect methane production on a seasonal scale but this impact might strongly depend on drying intensity and on the peat matrix, whose structure and physical properties influence moisture content. [ABSTRACT FROM AUTHOR]

Permafrost thaw in northern peatlands causes collapse of permafrost peat plateaus and thermokarst bog development, with potential impacts on atmospheric greenhouse gas exchange. Here, we measured methane and carbon dioxide fluxes over 3 years (including winters) using static chambers along two permafrost thaw transects in northwestern Canada, spanning young (~30 years since thaw), intermediate and mature thermokarst bogs (~200 years since thaw). Young bogs were wetter, warmer and had more hydrophilic vegetation than mature bogs. Methane emissions increased with wetness and soil temperature (40 cm depth) and modelled annual estimates were greatest in the young bog during the warmest year and lowest in the mature bog during the coolest year (21 and 7 g C-CH 4  m -2  year -1 , respectively). The dominant control on net ecosystem exchange (NEE) in the mature bog (between +20 and -54 g C-CO 2 m -2  year -1 ) was soil temperature (5 cm), causing net CO 2 loss due to higher ecosystem respiration (ER) in warmer years. In contrast, wetness controlled NEE in the young and intermediate bogs (between +55 and -95 g C-CO 2 m -2  year -1 ), where years with periodic inundation at the beginning of the growing season caused greater reduction in gross primary productivity than in ER leading to CO 2 loss. Winter fluxes (November-April) represented 16% of annual ER and 38% of annual CH 4 emissions. Our study found NEE of thermokarst bogs to be close to neutral and rules out large CO 2 losses under current conditions. However, high CH 4 emissions after thaw caused a positive net radiative forcing effect. While wet conditions favouring high CH 4 emissions only persist for the initial young bog period, we showed that continued climate warming with increased ER, and thus, CO 2 losses from the mature bog can cause net positive radiative forcing which would last for centuries after permafrost thaw., (© 2024 The Author(s). Global Change Biology published by John Wiley & Sons Ltd.)

Tramadol is an important minor opioid prescribed for pain management. In this study, we analyzed the well-known impact of CYP2D6 genetic variation and 60 additional variants in eight candidate genes (i.e., ABCG2, SLCO1B1, CYP2D6, CYP2B6, CYP2C19, CYP2C9, CYP3A5, and CYP3A4) on tramadol efficacy and safety. Some 108 patients with pain after surgery admitted to a post-anesthesia care unit (PACU) and prescribed tramadol were recruited. They were genotyped, and tramadol M1/M2 metabolite concentrations were determined by a newly validated HPLC-MS/MS method. CYP2D6 intermediate (IM) and poor (PM) metabolizers showed lower M1 concentrations adjusted for dose/weight at 30 and 120 min compared to ultrarapid (UM) and normal (NM) metabolizers (univariate p < 0.001 and 0.020, multivariate p < 0.001 and 0.001, unstandardized β coefficients = 0.386 and 0.346, R 2  = 0.146 and 0.120, respectively). CYP2B6 PMs (n = 10) were significantly related to a higher reduction in pain 30 min after tramadol intake (univariate p = 0.038, multivariate p = 0.016, unstandardized β coefficient = 0.224, R 2  = 0.178), to lower PACU admission time (p = 0.007), and to lower incidence of adverse drug reactions (p = 0.038) compared to the other phenotypes. CYP3A4 IMs and PMs showed a higher prevalence of drowsiness and dizziness (p = 0.028 and 0.005, respectively). Our results suggest that the interaction of CYP2B6 and CYP2D6 phenotypes may be clinically relevant, pending validation of these results in large, independent cohorts. Additional research is required to clarify the impact of CYP3A4 genetic variation on tramadol response., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Resistance to cucumber mosaic virus (CMV) in melon (Cucumis melo L.) has been described in several exotic accessions and is controlled by a recessive resistance gene, cmv1, that encodes a vacuolar protein sorting 41 (CmVPS41). cmv1 prevents systemic infection by restricting the virus to the bundle sheath cells, preventing viral phloem entry. CmVPS41 from different resistant accessions carries two causal mutations, either a G85E change, found in Pat-81 and Freeman's cucumber, or L348R, found in PI161375, cultivar Songwhan Charmi (SC). Here, we analyzed the subcellular localization of CmVPS41 in Nicotiana benthamiana and found differential structures in resistant and susceptible accessions. Susceptible accessions showed nuclear and membrane spots and many transvacuolar strands, whereas the resistant accessions showed many intravacuolar invaginations. These specific structures colocalized with late endosomes. Artificial CmVPS41 carrying individual mutations causing resistance in the genetic background of CmVPS41 from the susceptible variety Piel de Sapo (PS) revealed that the structure most correlated with resistance was the absence of transvacuolar strands. Coexpression of CmVPS41 with viral movement proteins, the determinant of virulence, did not change these localizations; however, infiltration of CmVPS41 from either SC or PS accessions in CMV-infected N. benthamiana leaves showed a localization pattern closer to each other, with up to 30% cells showing some membrane spots in the CmVPS41SC and fewer transvacuolar strands (reduced from a mean of 4 to 1-2) with CmVPS41PS. Our results suggest that the distribution of CmVPS41PS in late endosomes includes transvacuolar strands that facilitate CMV infection and that CmVPS41 re-localizes during viral infection., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Vast stores of millennial-aged soil carbon (MSC) in permafrost peatlands risk leaching into the contemporary carbon cycle after thaw caused by climate warming or increased wildfire activity. Here we tracked the export and downstream fate of MSC from two peatland-dominated catchments in subarctic Canada, one of which was recently affected by wildfire. We tested whether thermokarst bog expansion and deepening of seasonally thawed soils due to wildfire increased the contributions of MSC to downstream waters. Despite being available for lateral transport, MSC accounted for ≤6% of dissolved organic carbon (DOC) pools at catchment outlets. Assimilation of MSC into the aquatic food web could not explain its absence at the outlets. Using δ 13 C-Δ 14 C-δ 15 N-δ 2 H measurements, we estimated only 7% of consumer biomass came from MSC by direct assimilation and algal recycling of heterotrophic respiration. Recent wildfire that caused seasonally thawed soils to reach twice as deep in one catchment did not change these results. In contrast to many other Arctic ecosystems undergoing climate warming, we suggest waterlogged peatlands will protect against downstream delivery and transformation of MSC after climate- and wildfire-induced permafrost thaw., (© 2021 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Despite occupying a small fraction of the landscape, fluvial networks are disproportionately large emitters of CO 2 and CH 4 , with the potential to offset terrestrial carbon sinks. Yet the extent of this offset remains uncertain, because current estimates of fluvial emissions often do not integrate beyond individual river reaches and over the entire fluvial network in complex landscapes. Here we studied broad patterns of concentrations and isotopic signatures of CO 2 and CH 4 in 50 streams in the western boreal biome of Canada, across an area of 250,000 km 2 . Our study watersheds differ starkly in their geology (sedimentary and shield), permafrost extent (sporadic to extensive discontinuous) and land cover (large variability in lake and wetland extents). We also investigated the effect of wildfire, as half of our study streams drained watersheds affected by megafires that occurred 3 years prior. Similar to other boreal regions, we found that stream CO 2 concentrations were primarily associated with greater terrestrial productivity and warmer climates, and decreased downstream within the fluvial network. No effects of recent wildfire, bedrock geology or land cover composition were found. The isotopic signatures suggested dominance of biogenic CO 2 sources, despite dominant carbonate bedrock in parts of the study region. Fluvial CH 4 concentrations had a high variability which could not be explained by any landscape factors. Estimated fluvial CO 2 emissions were 0.63 (0.09-6.06, 95% CI) and 0.29 (0.17-0.44, 95% CI) g C m -2  year -1 at the landscape scale using a stream network modelling and a mass balance approach, respectively, a small but potentially important component of the landscape C balance. These fluvial CO 2 emissions are lower than in other northern regions, likely due to a drier climate. Overall, our study suggests that fluvial CO 2 emissions are unlikely to be sensitive to altered fire regimes, but that warming and permafrost thaw will increase emissions significantly., (© 2019 John Wiley & Sons Ltd.)

Carbon release from thawing permafrost soils could significantly exacerbate global warming as the active-layer deepens, exposing more carbon to decay. Plant community and soil properties provide a major control on this by influencing the maximum depth of thaw each summer (active-layer thickness; ALT), but a quantitative understanding of the relative importance of plant and soil characteristics, and their interactions in determine ALTs, is currently lacking. To address this, we undertook an extensive survey of multiple vegetation and edaphic characteristics and ALTs across multiple plots in four field sites within boreal forest in the discontinuous permafrost zone (NWT, Canada). Our sites included mature black spruce, burned black spruce and paper birch, allowing us to determine vegetation and edaphic drivers that emerge as the most important and broadly applicable across these key vegetation and disturbance gradients, as well as providing insight into site-specific differences. Across sites, the most important vegetation characteristics limiting thaw (shallower ALTs) were tree leaf area index (LAI), moss layer thickness and understory LAI in that order. Thicker soil organic layers also reduced ALTs, though were less influential than moss thickness. Surface moisture (0-6 cm) promoted increased ALTs, whereas deeper soil moisture (11-16 cm) acted to modify the impact of the vegetation, in particular increasing the importance of understory or tree canopy shading in reducing thaw. These direct and indirect effects of moisture indicate that future changes in precipitation and evapotranspiration may have large influences on ALTs. Our work also suggests that forest fires cause greater ALTs by simultaneously decreasing multiple ecosystem characteristics which otherwise protect permafrost. Given that vegetation and edaphic characteristics have such clear and large influences on ALTs, our data provide a key benchmark against which to evaluate process models used to predict future impacts of climate warming on permafrost degradation and subsequent feedback to climate., (© 2016 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.)

Cucumber mosaic virus (CMV) has the broadest host range among plant viruses, causing enormous losses in agriculture. In melon, strains of subgroup II are unable to establish a systemic infection in the near-isogenic line SC12-1-99, which carries the recessive resistance gene cmv1 from the accession PI 161375, cultivar 'Songwhan Charmi'. Strains of subgroup I overcome cmv1 resistance in a manner dependent on the movement protein. We characterized the resistance conferred by cmv1 and established that CMV-LS (subgroup II) can move from cell to cell up to the veins in the inoculated leaf, but cannot enter the phloem. Immunogold labelling at transmission electron microscopy level showed that CMV-LS remains restricted to the bundle sheath (BS) cells in the resistant line, and does not invade vascular parenchyma or intermediary cells, whereas, in the susceptible line 'Piel de Sapo' (PS), the virus invades all vein cell types. These observations indicate that the resistant allele of cmv1 restricts systemic infection in a virus strain- and cell type-specific manner by acting as an important gatekeeper for virus progression from BS cells to phloem cells. Graft inoculation experiments showed that CMV-LS cannot move from the infected PS stock into the resistant cmv1 scion, thus suggesting an additional role for cmv1 related to CMV transport within or exit from the phloem. The characterization of this new form of recessive resistance, based on a restriction of virus systemic movement, opens up the possibility to design alternative approaches for breeding strategies in melon., (© 2015 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

The quantitative impact of intense drought and rewetting on gas exchange in ombrotrophic bogs is still uncertain. In particular, we lack studies investigating multitudes of sites with different soil properties and nitrogen (N) and sulfur (S) deposition under consistent environmental conditions. We explored the timing and magnitude of change in CO2 (Respiration, Gross Primary Production - GPP, and Net Exchange - NE) and CH4 fluxes during an initial wet, a prolonged dry (~100 days), and a subsequent wet period (~230 days) at 12 °C in 14 Sphagnum peat mesocosms collected in hollows from bogs in the UK, Ireland, Poland, and Slovakia. The relationship of N and S deposition with GPP, respiration, and CH4 exchange was investigated. Nitrogen deposition increased CO2 fluxes and GPP more than respiration, at least up to about 15 kg N ha(-1)  yr(-1) . All mesocosms became CO2 sources during drying and most of them when the entire annual period was considered. Response of GPP to drying was faster than that of respiration and contributed more to the change in NE; the effect was persistent and few sites recovered "predry" GPP by the end of the wet phase. Respiration was higher during the dry phase, but did not keep increasing as WT kept falling and peaked within the initial 33 days of drying; the change was larger when differences in humification with depth were small. CH4 fluxes strongly peaked during early drought and water table decline. After rewetting, methanogenesis recovered faster in dense peats, but CH4 fluxes remained low for several months, especially in peats with higher inorganic reduced sulfur content, where sulfate was generated and methanogenesis remained suppressed. Based on a range of European sites, the results support the idea that N and S deposition and intense drought can substantially affect greenhouse gas exchange on the annual scale., (© 2016 John Wiley & Sons Ltd.)

The resistance to a set of strains of Cucumber mosaic virus (CMV) in the melon accession PI 161375, cultivar 'Songwhan Charmi', is dependent on one recessive gene, cmv1, which confers total resistance, whereas a second set of strains is able to overcome it. We tested 11 strains of CMV subgroups I and II in the melon line SC12-1-99, which carries the gene cmv1, and showed that this gene confers resistance to strains of subgroup II only and that restriction is not related to either viral replication or cell-to-cell movement. This is the first time that a resistant trait has been correlated with CMV subgroups. Using infectious clones of the CMV strains LS (subgroup II) and FNY (subgroup I), we generated rearrangements and viral chimaeras between both strains and established that the determinant of virulence against the gene cmv1 resides in the first 209 amino acids of the movement protein, as this region from FNY is sufficient to confer virulence to the LS clone in the line SC12-1-99. A comparison of the sequences of the strains of both subgroups in this region shows that there are five main positions shared by all strains of subgroup II, which are different from those of subgroup I. Site-directed mutagenesis of the CMV-LS clone to substitute these residues for those of CMV-FNY revealed that a combination of four of these changes [the group 64-68 (SNNLL to HGRIA), and the point mutations R81C, G171T and A195I] was required for a complete gain of function of the LS MP in the resistant melon plant., (© 2014 BSPP AND JOHN WILEY & SONS LTD.)

Peroxiredoxins (Prx) catalyse the reduction of hydrogen peroxide (H2O2) and, in association with catalases and other peroxidases, may participate in signal transduction by regulating intercellular H2O2 concentration that in turn can control gene transcription and cell signaling. Using virus-induced-gene-silencing (VIGS), 2-Cys Peroxiredoxin (2CysPrx) family and type-II Peroxiredoxin B (PrxIIB) gene were silenced in Nicotiana benthamiana, to study the impact that the loss of function of each Prx would have in the antioxidant system under control (22 °C) and severe heat stress conditions (48 °C). The results showed that both Prxs, although in different organelles, influence the regeneration of ascorbate to a significant extent, but with different purposes. 2CysPrx affects abscisic acid (ABA) biosynthesis through ascorbate, while PrxIIB does it probably through the xanthophyll cycle. Moreover, 2CysPrx is key in H2O2 scavenging and in consequence in the regulation of ABA signaling downstream of reactive oxygen species and PrxIIB provides an important assistance for H2O2 peroxisome scavenges., (© 2014 Institute of Botany, Chinese Academy of Sciences.)

Introduction: Emergence of HIV-1 drug resistance may limit the sustained benefits of antiretroviral therapy (ART) in settings with limited laboratory monitoring and drug options. The objective is to implement the surveillance of drug resistance and subtypes in HIV-1 patients failing ART in Cuba., Methods: This study compiled clinical and genotypic drug resistance data 588 ART-experienced HIV-1 patients attending a clinical center in Havana in 2009-2013. Drug resistance testing was performed as part of routine clinical care. Drug resistance mutations and levels were determined using Rega version 8.0.2., Results: Eighty-three percent received solely ART containing at least three drugs. Patients from 2009 to 2010 were longer treated (median: 4.9 vs 2.7 years) and exposed to more ART regimens (median: 4 vs 2 regimens) compared to patients from 2011-2013. Nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside RTI (NNRTI) and PI mutations were present in 83.5, 77.4 and 52.0%. Full-class resistance (FCR) to NRTI, NNRTI, PI and multidrug resistance (MDR) were detected in 25.0, 33.7, 11.4 and 6.3%. FCR to NRTI, NNRTI, PI and MDR were present in 12.8, 28.7, 0 and 0% after first-line failure (164 patients) and in 23.1, 34.6, 3.8 and 3.1% after second-line failure (130 patients). Subtype B (32.5%), BG recombinants (19.6%) and CRF19&#95;cpx (16.2%) were the most prevalent genetic forms. Subtype distribution did not change significantly between 2009-2010 and 2011-2013, except for BG recombinants that increased from 12.2 to 21.3% (p=0.002)., Conclusions: Our study found a high prevalence of drug resistance and supports the need for appropriate laboratory monitoring in clinical practice and access to drug options in case of virological failure.

Introduction: Aortic valve replacement in patients with severe aortic stenosis may be complicated by complete atrioventricular block (CAVB), requiring a permanent pacemaker (PPM) implantation. Predicting this complication could help to plan the surgical., Objective: Determine whether electrocardiography and echocardiography are useful methods for predicting the need for PPM., Material and Methods: A retrospective, observational and transversal study was performed. An echocardiography based semi-quantitative classification was implemented to graduate the extent of calcification of the aortic valve., Results: We included 95 patients; 10 of them required PPM implantation (10.52%). In the pre-surgical basal electrocardiogram we observed that 90% of patients that required PPM had conduction abnormalities as opposed to only 24.7% in the other group, p = 0.001. A 1st and 2nd degree AV block (AVB 1 and 2) was identified in 8 patients that subsequently needed PPM (80%) vs. 5 patients (5.9%), in the group that did not required it, p = 0.001.OR 41.7, IC 95% 6.5-68. We found a grade 3 calcification extent in 80% of patients who required PPM implant compared with only 17.6% of patients in the other group, p = 0.04, OR 4.8, IC 95% 0.76-29. The AVB 1 and 2 were the single predictor in multivariate analysis but the calcification 3 + AVB 1 and 2, increased sensibility., Concluison: In patients with aortic stenosis in whom aortic valve replacement was performed, identifying AVB 1 and 2 on the basal electrocardiogram is a useful tool in order to identify requirement of PPM. The grade 3 of calcification extent increased the sensibility of this prediction.

In Cuba, antiretroviral therapy rollout started in 2001 and antiretroviral therapy coverage has reached almost 40% since then. The objectives of this study were therefore to analyze subtype distribution, and level and patterns of drug resistance in therapy-naive HIV-1 patients. Four hundred and one plasma samples were collected from HIV-1 therapy-naive patients in 2003 and in 2007-2011. HIV-1 drug resistance genotyping was performed in the pol gene and drug resistance was interpreted according to the WHO surveillance drug-resistance mutations list, version 2009. Potential impact on first-line therapy response was estimated using genotypic drug resistance interpretation systems HIVdb version 6.2.0 and Rega version 8.0.2. Phylogenetic analysis was performed using Neighbor-Joining. The majority of patients were male (84.5%), men who have sex with men (78.1%) and from Havana City (73.6%). Subtype B was the most prevalent subtype (39.3%), followed by CRF20-23-24&#95;BG (19.5%), CRF19&#95;cpx (18.0%) and CRF18&#95;cpx (10.3%). Overall, 29 patients (7.2%) had evidence of drug resistance, with 4.0% (CI 1.6%-4.8%) in 2003 versus 12.5% (CI 7.2%-14.5%) in 2007-2011. A significant increase in drug resistance was observed in recently HIV-1 diagnosed patients, i.e. 14.8% (CI 8.0%-17.0%) in 2007-2011 versus 3.8% (CI 0.9%-4.7%) in 2003 (OR 3.9, CI 1.5-17.0, p=0.02). The majority of drug resistance was restricted to a single drug class (75.8%), with 55.2% patients displaying nucleoside reverse transcriptase inhibitor (NRTI), 10.3% non-NRTI (NNRTI) and 10.3% protease inhibitor (PI) resistance mutations. Respectively, 20.7% and 3.4% patients carried viruses containing drug resistance mutations against NRTI+NNRTI and NRTI+NNRTI+PI. The first cases of resistance towards other drug classes than NRTI were only detected from 2008 onwards. The most frequent resistance mutations were T215Y/rev (44.8%), M41L (31.0%), M184V (17.2%) and K103N (13.8%). The median genotypic susceptibility score for the commonly prescribed first-line therapies was 2.5. This analysis emphasizes the need to perform additional surveillance studies to accurately assess the level of transmitted drug resistance in Cuba, as the extent of drug resistance might jeopardize effectiveness of first-line regimens prescribed in Cuba and might necessitate the implementation of baseline drug resistance testing., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Emergence of HIV-1 drug resistance may limit the sustained benefits of antiretroviral therapy (ART) in settings with limited laboratory monitoring and drug options., Objectives: Surveillance of drug resistance and subtypes in HIV-1 patients failing ART in Cuba., Study Design: This study compiled data of ART-experienced HIV-1 patients attending a clinical center in Havana in 2003 and 2009-2011. The first period included results of a cross-sectional study, whereas in the second period genotyping was performed as part of routine care. Drug resistance mutations and levels were determined using HIVdb version 6.0.9., Results: Seventy-six percent received solely ART containing at least 3 drugs, of which 79.1% ever receiving unboosted protease inhibitors (PI). Patients from 2009 to 2011 were longer treated and exposed to more ART regimens. Subtype B (39%) and CRF19&#95;cpx (18%) were the most prevalent genetic forms. Subtype distribution did not change significantly between both periods, except for BG recombinants that increased from 6% to 14%. Nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside RTI (NNRTI) and PI mutations were present in 69.5%, 54.8% and 44.4%. Full-class resistance (FCR) to NRTI, NNRTI, PI and multidrug resistance (MDR) were detected in 31.8%, 37.9%, 18.5% and 15.4%. FCR to NRTI, NNRTI, PI and MDR were present in 9.8%, 14.1%, 0%, 0% after first-line failure and in 19.8%, 20.8%, 2.9% and 2.9% after second-line failure., Conclusions: Our study found a high prevalence of drug resistance and supports the need for appropriate laboratory monitoring in clinical practice and access to drug options in case of virological failure., (Copyright © 2012 Elsevier B.V. All rights reserved.)

AIDS is a major cause of death in the Caribbean, a region with a high prevalence of HIV. However, prevalence in Cuba's population aged 15 to 49 years, despite a slight increase in recent years, is considered extremely low (0.1%). At the close of 2010, 5692 Cuban patients were receiving antiretroviral therapy. SIDATRAT, an informatics system, was developed at the Pedro Kourí Tropical Medicine Institute in Havana to ensure proper monitoring and followup of drug administration. Functioning on a web platform utilizing an Apache server, PHP and MySQL, it records patients' general information, CD4 counts, viral load and data from other laboratory tests, as well as endoscopic and imaging studies. It also compiles information on their AIDS classification, opportunistic infections, HIV subtype and resistance studies, followup consultations, drug regimen, adverse reactions to medications, changes in drug combinations, and survival; and tracks total number of individuals under treatment. SIDATRAT follows the client-server philosophy and enables access by authorized users throughout Cuba via the health informatics network. SIDATRAT has been found effective in supporting quality care for persons living with HIV/AIDS and universal access to antiretroviral therapy, compiling most of the information needed for decisionmaking on patient health and therapies. SIDATRAT has been offered to the UNDP office in Havana for sharing with other developing countries that may wish to adapt or implement it.

To characterize the possible role of glutamate in the interaction between Hypothalamic Defense Area (HDA) and Parabrachial complex (PBc) nuclei, cardiorespiratory changes were analyzed in response to electrical stimulation of the HDA (1 ms pulses, 30-50 μA given at 100 Hz for 5s) before and after the microinjection of the nonspecific glutamate receptor antagonist kynurenic acid (50 nl, 5 nmol), NMDA receptor antagonist MK-801 (50 nl, 50 nmol), non-NMDA receptor antagonist CNQX (50 nl, 50 nmol) or metabotropic glutamate receptor antagonist MCPG (50 nl, 5 nmol) within the PBc. HDA stimulation evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (p<0.001) due to a decrease in expiratory time (p<0.01). The respiratory response was accompanied by a pressor (p<0.001) and a tachycardic response (p<0.001). Kynurenic acid within the lateral parabrachial region (lPB) abolished the tachycardia (p<0.001) and decreased the magnitude of blood pressure response (p<0.001) to HDA stimulation. Similarly, the magnitude of the tachycardia and the pressor response was decreased after the microinjection of MK-801 (p<0.01 and p<0.001, respectively) and CNQX (p<0.05 in both cases) into the lPB. Kynurenic acid microinjection in this region produced an inhibition of the tachypnea (p<0.001) to HDA stimulation but the respiratory response persisted unchanged after MK-801 or CNQX microinjection into the lPB. Kynurenic acid within the medial parabrachial region (mPB) abolished the tachycardia (p<0.01) and decreased the magnitude of the pressor response (p<0.001) to HDA stimulation. MK-801 and CNQX microinjection in this region decreased the magnitude of the tachycardia (p<0.05, in both cases) and pressor response (p<0.05, in both cases). The respiratory response evoked by HDA stimulation was not changed after the microinjection of kynurenic acid, MK-801 or CNQX within the mPB. No changes were observed in the cardiorespiratory response evoked to HDA stimulation after MCPG microinjection within lPB and mPB. These results indicate that glutamate PBc receptors are involved in the cardiorespiratory response evoked from the HDA. The possible mechanisms involved in these interactions are discussed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A laboratory experiment was conducted to identify key hydrocarbon degraders from a marine oil spill sample (Prestige fuel oil), to ascertain their role in the degradation of different hydrocarbons, and to assess their biodegradation potential for this complex heavy oil. After a 17-month enrichment in weathered fuel, the bacterial community, initially consisting mainly of Methylophaga species, underwent a major selective pressure in favor of obligate hydrocarbonoclastic microorganisms, such as Alcanivorax and Marinobacter spp. and other hydrocarbon-degrading taxa (Thalassospira and Alcaligenes), and showed strong biodegradation potential. This ranged from >99% for all low- and medium-molecular-weight alkanes (C(15)-C(27)) and polycyclic aromatic hydrocarbons (C(0)- to C(2)- naphthalene, anthracene, phenanthrene, dibenzothiophene, and carbazole), to 75-98% for higher molecular-weight alkanes (C(28)-C(40)) and to 55-80% for the C(3) derivatives of tricyclic and tetracyclic polycyclic aromatic hydrocarbons (PAHs) (e.g., C(3)-chrysenes), in 60 days. The numbers of total heterotrophs and of n-alkane-, aliphatic-, and PAH degraders, as well as the structures of these populations, were monitored throughout the biodegradation process. The salinity of the counting medium affects the counts of PAH degraders, while the carbon source (n-hexadecane vs. a mixture of aliphatic hydrocarbons) is a key factor when counting aliphatic degraders. These limitations notwithstanding, some bacterial genera associated with hydrocarbon degradation (mainly belonging to α- and γ-Proteobacteria, including the hydrocarbonoclastic Alcanivorax and Marinobacter) were identified. We conclude that Thalassospira and Roseobacter contribute to the degradation of aliphatic hydrocarbons, whereas Mesorhizobium and Muricauda participate in the degradation of PAHs.

INTRODUCTION Cuba has an HIV prevalence of 0.1% in the population aged 15 to 49 years, very low despite increased incidence in recent years. In 2001, domestically-produced generic antiretroviral therapy was introduced and there has been complete coverage since 2003. In 2006, 1986 people with HIV/AIDS were receiving ART; by 2009, that figure reached 5034. Adherence to antiretroviral therapy is fundamental: nonadherence leads to treatment failure, development of resistance, progression to AIDS, and death. OBJECTIVE Measure levels of treatment adherence and its predictive factors in persons with HIV/AIDS receiving antiretroviral therapy in 2006 in Cuba. METHODS A cross-sectional study was carried out in 2006 of Cuban HIV-positive individuals receiving antiretroviral therapy. A sample size of 876 was calculated using two-stage sampling (first by strata, and then by simple random sampling in each stratum). An anonymous structured questionnaire was administered to participants. Reporting of doses taken on each of the three days and in the week preceding the survey was recoded into five categories. Participants were considered highly adherent if they reported taking ≥95.0% of their medication as prescribed. Reasons for nonadherence were described and logistic regression modeling used to develop hypotheses on associations between high adherence and its predictive factors. RESULTS Interviews were obtained with 847 individuals, 70.6% of whom self reported high adherence. There were no significant differences between highly adherent and less adherent patients with regard to sex, place of residence, treatment setting, time of diagnosis, or length of treatment. Variables associated with high adherence were communication with the specialist physician, change in treatment, memory, self-efficacy, as well as commitment to and opinions about treatment. CONCLUSIONS In Cuba, where treatment is free of charge to patients, adherence is good. Treatment adherence might be improved by achieving a closer doctor-patient relationship; taking measures to motivate patients and promote self-efficacy and commitment to treatment; publicizing treatment outcomes; and providing assistance to patients to help them remember their medication schedule. Further studies are required to determine current adherence levels; and longitudinal research to determine adherence over time.

As long as there is no cure for AIDS, the only effective means of containing its spread is prevention, primarily through public education. Cuba's AIDS Prevention Group is a community-based organization whose main purpose is to support the National HIV/AIDS Program's prevention and education efforts. The Group's Memorias Project uses the creation and display of memorial quilts to put a human face on AIDS statistics and stimulate public reflection on issues related to the disease and society.

BG intersubtype recombinants represented 11.6% of HIV-1 isolates in a recent survey in Cuba based on pol sequences, most of them forming a single clade further subdivided into 3 subclades. Here, we analyze 8 near full-length genomes and 1 gag-pol sequence from epidemiologically unlinked Cuban BG recombinants from these 3 subclades (3 from each). Near full-length sequences were also obtained from 3 subtype G and 2 subtype B Cuban viruses. Phylogenetic relationships were estimated via maximum likelihood, and mosaic structures of the recombinants were inferred with the bootscanning, MaxChi, Genconv, and GARD methods. For the near full-length genomes, all recombinants formed a strongly supported clade further subdivided into the same subclades previously defined in pol. Mosaic structures were identical within each subclade and different among subclades, although 5 breakpoints were coincident among all recombinants. Individual phylogenetic trees for nonrecombinant fragments (concatenated B and G subtype segments) indicated a common ancestry for the parental viruses and their relationships to local subtype B and G strains. These results allow us to identify 3 new BG intersubtype circulating recombinant forms in Cuba derived from a common recombinant ancestor, which originated from B and G subtype parental strains circulating in Cuba.

The main objective of this study is to evaluate the prevalence of resistance-associated mutations to reverse transcriptase (RT) and protease (PR) inhibitors (I) 2 years after the introduction of antiretroviral treatment in Cuba, analyzing the mutations corresponding to different HIV-1 genetic forms circulating in Cuba. A total of 425 plasma samples were collected in 2003, corresponding to 175 (41.2%) subtype B and 250 (58.8%) non-B genetic forms, including 56 (22.4 %) non-B subtypes, 112 (44.8%) circulating recombinant forms (CRFs), and 82 (32.8%) unique RFs (URFs). Of these, 175 (41.2%) patients were under highly active antiretroviral therapy (HAART) and 250 (58.8%) were treatment-naive. The presence of RT and PR resistance-associated mutations was established by sequencing. Levels of resistance were evaluated according to the Stanford Database program (http://hivdb.stanford.edu). The prevalence of resistance to RTI was 52.2% among RTI-treated patients, 51.5% for subtype B, and 53.2% for non-B genetic forms, including CRF18&#95;cpx, CRF19&#95;cpx, subtype C, and BG URF. In treatment-naive patients it was 6.4% in subtype B and 4.2% in non-B subtypes and RFs. The prevalence of resistance to PRI was 30% among PRI-treated patients, 28% in subtype B and 31% in non-B genetic forms, and 3.2% among treatment-naive subjects, mostly BG recombinants. In conclusion, significant differences in the prevalence of resistance to RTI and PRI were not detected among the most frequent genetic forms from treated patients, suggesting that the genetic diversity of HIV-1 in Cuba does not play a main role in the development of resistance to antiretroviral drugs. The presence of transmitted resistance mutations supports the study of resistance at baseline of treatment.

Highly diverse HIV-1 genetic forms are circulating in Cuba, including subtypes B and G and two recombinant forms of African origin (CRF18&#95;cpx and CRF19&#95;cpx). Here we phylogenetically analyze pol sequences from a large collection of recent samples from Cuba, corresponding to 425 individuals from all Cuban provinces, which represents approximately 12% of prevalent infections in the country. RNA from plasma was used to amplify a pol segment by reverse transcription-polymerase chain reaction; phylogenetic analyses were performed with neighbour-joining trees and bootscanning. The distribution of genetic forms was subtype B, 41.2%; CRF19&#95;cpx, 18.4%; BG recombinants, 11.6%; CRF18&#95;cpx, 7.1%; subtype C, 6.1%; subtype G, 3.8%; B/CRF18 recombinants, 2.6%; subtype H, 2.1%; B/CRF19 recombinants, 1.7%; and others, 5.4%. Seventy-five (17.6%) viruses were recombinant between genetic forms circulating in Cuba. In logistic regression analyses, adjusting by gender and region, subtype B was more prevalent (OR 5.0, 95% CI 2.0-12.3) and subtype G less prevalent (OR 0.1, 95% CI 0.0-0.5) among men who have sex with men (MSM) than among heterosexuals. Within the main genetic forms of Cuba there were phylogenetic subclusters, several of which correlated with risk exposure or region. BG recombinants formed three phylogenetically related subclusters, corresponding to three different mosaic structures; most of these recombinants were from MSM from Havana City, among whom they have expanded recently, reaching 31% HIV-1 infections diagnosed in 2003. This study confirms the high HIV-1 diversity and frequent recombination in Cuba and reveals the recent expansion of diverse related BG recombinant forms in this country.