Background Acute pancreatitis is a common complication of ERCP. Several randomized, controlled trials (RCTs) have evaluated the use of pancreatic stents in the prevention of post-ERCP pancreatitis ...with varying results. Objective We conducted a meta-analysis and systematic review to assess the role of prophylactic pancreatic stents for prevention of post-ERCP pancreatitis. Design MEDLINE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, PubMed, and recent abstracts from major conference proceedings were searched. RCTs and retrospective or prospective, nonrandomized studies comparing prophylactic stent with placebo or no stent for post-ERCP pancreatitis were included for the meta-analysis and systematic review. Standard forms were used to extract data by 2 independent reviewers. The effect of stents (for RCTs) was analyzed by calculating pooled estimates of post-ERCP pancreatitis, hyperamylasemia, and grade of pancreatitis. Separate analyses were performed for each outcome by using the odds ratio (OR) or weighted mean difference. Random- or fixed-effects models were used. Publication bias was assessed by funnel plots. Heterogeneity among studies was assessed by calculating I2 measure of inconsistency. Setting Systematic review and meta-analysis of patients undergoing pancreatic stent placement for prophylaxis against post-ERCP pancreatitis. Patients Adult patients undergoing ERCP. Interventions Pancreatic stent placement for the prevention of post-ERCP pancreatitis. Main Outcome Measurements Post-ERCP pancreatitis, hyperamylasemia, and complications after pancreatic stent placement. Results Eight RCTs (656 subjects) and 10 nonrandomized studies met the inclusion criteria (4904 subjects). Meta-analysis of the RCTs showed that prophylactic pancreatic stents decreased the odds of post-ERCP pancreatitis (odds ratio, 0.22; 95% CI, 0.12-0.38; P < .01). The absolute risk difference was 13.3% (95% CI, 8.8%-17.8%). The number needed to treat was 8 (95% CI, 6-11). Stents also decreased the level of hyperamylasemia (WMD, −309.22; 95% CI, −350.95 to −267.49; P ≤ .01). Similar findings were also noted from the nonrandomized studies. Limitations Small sample size of some trials, different types of stents used, inclusion of low-risk patients in some studies, and lack of adequate study of long-term complications of pancreatic stent placement. Conclusions Pancreatic stent placement decreases the risk of post-ERCP pancreatitis and hyperamylasemia in high-risk patients.
We consider finite-temperature
SU
(2) gauge theory in the continuum formulation, which necessitates the choice of a gauge fixing. Choosing the Landau gauge, the existing gauge copies are taken into ...account by means of the Gribov–Zwanziger quantization scheme, which entails the introduction of a dynamical mass scale (Gribov mass) directly influencing the Green functions of the theory. Here, we determine simultaneously the Polyakov loop (vacuum expectation value) and Gribov mass in terms of temperature, by minimizing the vacuum energy w.r.t. the Polyakov-loop parameter and solving the Gribov gap equation. Inspired by the Casimir energy-style of computation, we illustrate the usage of Zeta function regularization in finite-temperature calculations. Our main result is that the Gribov mass directly feels the deconfinement transition, visible from a cusp occurring at the same temperature where the Polyakov loop becomes nonzero. In this exploratory work we mainly restrict ourselves to the original Gribov–Zwanziger quantization procedure in order to illustrate the approach and the potential direct link between the vacuum structure of the theory (dynamical mass scales) and (de)confinement. We also present a first look at the critical temperature obtained from the refined Gribov–Zwanziger approach. Finally, a particular problem for the pressure at low temperatures is reported.
The understanding of acclimation strategies to low temperature and water availability is decisive to ensure coffee crop sustainability, since these environmental conditions determine the suitability ...of cultivation areas. In this context, the impacts of single and combined exposure to drought and cold were evaluated in three genotypes of the two major cropped species, Coffea arabica cv. Icatu, Coffea canephora cv. Apoatã, and the hybrid Obatã. Crucial traits of plant resilience to environmental stresses have been examined: photosynthesis, lipoperoxidation and the antioxidant response. Drought and/or cold promoted leaf dehydration, which was accompanied by stomatal and mesophyll limitations that impaired leaf C-assimilation in all genotypes. However, Icatu showed a lower impact upon stress exposure and a faster and complete photosynthetic recovery. Although lipoperoxidation was increased by drought (Icatu) and cold (all genotypes), it was greatly reduced by stress interaction, especially in Icatu. In fact, although the antioxidative system was reinforced under single drought and cold exposure (e.g., activity of enzymes as Cu,Zn-superoxide dismutase, ascorbate peroxidase, APX, glutathione reductase and catalase, CAT), the stronger increases were observed upon the simultaneous exposure to both stresses, which was accompanied with a transcriptional response of some genes, namely related to APX. Complementary, non-enzyme antioxidant molecules were promoted mostly by cold and the stress interaction, including α-tocopherol (in C. arabica plants), ascorbate (ASC), zeaxanthin, and phenolic compounds (all genotypes). In general, drought promoted antioxidant enzymes activity, whereas cold enhanced the synthesis of both enzyme and non-enzyme antioxidants, the latter likely related to a higher need of antioxidative capability when enzyme reactions were probably quite repressed by low temperature. Icatu showed the wider antioxidative capability, with the triggering of all studied antioxidative molecules by drought (except CAT), cold, and, particularly, stress interaction (except ASC), revealing a clear stress cross-tolerance. This justified the lower impacts on membrane lipoperoxidation and photosynthetic capacity under stress interaction conditions, related to a better ROS control. These findings are also relevant to coffee water management, showing that watering in the cold season should be largely avoided.
Anthrax is an infectious disease caused by Bacillus anthracis, a bioterrorism agent that develops resistance to clinically used antibiotics. Therefore, alternative mechanisms of action remain a ...challenge. Herein, we disclose deoxy glycosides responsible for specific carbohydrate-phospholipid interactions, causing phosphatidylethanolamine lamellar-to-inverted hexagonal phase transition and acting over B. anthracis and Bacillus cereus as potent and selective bactericides. Biological studies of the synthesized compound series differing in the anomeric atom, glycone configuration and deoxygenation pattern show that the latter is indeed a key modulator of efficacy and selectivity. Biomolecular simulations show no tendency to pore formation, whereas differential metabolomics and genomics rule out proteins as targets. Complete bacteria cell death in 10 min and cellular envelope disruption corroborate an effect over lipid polymorphism. Biophysical approaches show monolayer and bilayer reorganization with fast and high permeabilizing activity toward phosphatidylethanolamine membranes. Absence of bacterial resistance further supports this mechanism, triggering innovation on membrane-targeting antimicrobials.
Along with population growth, global climate change represents a critical threat to agricultural production, compromising the goal of achieving food and nutrition security for all. It is urgent to ...create sustainable and resilient agri-food systems capable of feeding the world without debilitating the planet. The Food and Agriculture Organization of the United Nations (FAO) refers to pulses as a superfood, as one of the most nutritious crops with high health benefits. Considered to be low-cost, many can be produced in arid lands and have an extended shelf-life. Their cultivation helps reduce greenhouse gases and increases carbon sequestration, also improving soil fertility. Cowpea,
(L.) Walp. is particularly drought tolerant, with a wide diversity of landraces adapted to different environments. Considering the importance of knowing and valuing the genetic variability of this species in Portugal, this study assessed the impact of drought on four landraces of cowpea (L1 to L4) from different regions of the country and a national commercial variety (CV) as a reference. The development and evaluation of morphological characteristics were monitored in response to terminal drought (imposed during the reproductive phase), and its effects were evaluated on the yield and quality of the produced grain, namely the weight of 100 grains, color, protein content, and soluble sugars. Under drought conditions, the landraces L1 and L2 showed early maturation as a strategy to avoid water deficit. Morphological alteration of the aerial part of the plants was evident in all genotypes, with a rapid reduction in the number of leaves and a reduction in the number of flowers and pods by between 44 and 72%. The parameters of grain quality, the weight of 100 grains, color, protein, and soluble sugars did not vary significantly, except for sugars of the raffinose family that is associated with the adaptive mechanisms of plants to drought. The performance and maintenance of the evaluated characteristics reflect the adaptation acquired in the past by exposure to the Mediterranean climate, highlighting the potential agronomic and genetic value, still little exploited, that could contribute to production stability, preserved nutritional value, and food safety under water stress.
Bread wheat (Triticum aestivum L.) is a major staple crop, and more adapted varieties are needed to ensure productivity under unpredictable stress scenarios resulting from climate changes. In the ...development of new genotypes, root system traits are essential since roots have a key function in water and nutrient uptake, and root architecture determines the plant’s ability to spatially explore the soil resources. Genetic variation in wheat root system may be assessed at the early stages of development. This study evaluates in vitro and at the seedling stage, the genetic diversity of root growth angle (RGA), seminal root number (SRN), and radicle length (RadL) in 30 bread wheat genotypes from different origins and belonging to distinct evolutive or breeding groups. SRN and RadL were analyzed at 1, 2, 3 and 6 days after sowing (DAS) and RGA was measured through the angle between the first pair of seminal roots. A large variability was found in RGA values that ranged from 63° to 122°. Although differences were found between genotypes within the same groups, the narrower angles tended to occur among landraces, while the higher RGA values were observed in advanced lines and Australian varieties. Differences were also observed as regards the SRN (1.0–3.0, 2.7–4.7, 3.2–5.0 and 4.4–6.3 at 1, 2, 3 and 6 DAS, respectively) and RadL (0.1–1.5, 2.1–5.0, 4.0–7.5 and 5.1–13.7 cm at 1, 2, 3 and 6 DAS, respectively). Genetic variability in root traits at seedling stage allows more rapid selection of genotypes better adapted to environmental and soil constraints, necessary to Portuguese Wheat Breeding Program. It will also contribute to the definition of wheat ideotypes with improved performance under Mediterranean climate conditions.
Tuberculosis (TB) is a disease that plagues the frailest members of society. We have developed a family of
-alkyl nitrobenzamides that exhibit promising antitubercular activities and can be ...considered a structural simplification of known inhibitors of decaprenylphosphoryl-β-D-ribofuranose 2'-oxidase (DprE1), an essential
(Mtb) enzyme and an emergent antitubercular target. Hereby, we report the development of these compounds via a simple synthetic methodology as well as their stability, cytotoxicity, and antitubercular activity. Studying their
activity revealed that the 3,5-dinitro and the 3-nitro-5-trifluoromethyl derivatives were the most active, and within these, the derivatives with intermediate lipophilicities presented the best activities (MIC of 16 ng/mL). Additionally, in an
macrophage model of infection, the derivatives with chain lengths of six and twelve carbon atoms presented the best results, exhibiting activity profiles comparable to isoniazid. Although the proof is not definite, the assessment of susceptibility over multiple mycobacterial species, together with the structure similarities with known inhibitors of this enzyme, support DprE1 as a likely target of action for the compounds. This idea is also reinforced by the docking studies, where the fit of our more active compounds to the DprE1 binding pocket is very similar to what was observed for known inhibitors like DNB1.
Tuberculosis (TB) continues to be a major global health challenge and a leading cause of death from infectious diseases. Inspired by the results from a previous work by our group on antimycobacterial
...-alkylnitrobenzamides, which are structurally related to the nitrobenzamide family of decaprenylphosphoryl-β-d-ribose oxidase (DprE1) inhibitors, the present study explored a broad array of substituted benzamides. We particularly focused on previously unexplored 3,5-dinitrobenzamide derivatives. Starting with 3,5-dinitrobenzoic acid, we synthesized a diverse library of amides, incorporating both linear and cyclic amine moieties and also assessed the impact of terminal aromatic groups connected through ether, ester, or amide bonds on the bioactivity of the compounds. The synthesis primarily utilized nucleophilic addition/elimination, S
2, and Mitsunobu reactions. The activity was impacted mainly by two structural features, the addition of an aromatic moiety as a terminal group and the type of linker. The most interesting compounds (
,
, and
, MIC = 0.031 μg/mL) exhibited activities against
(Mtb) H37Rv comparable to isoniazid. Complementary computational studies helped elucidate potential interactions with DprE1, enhancing our understanding of the molecular basis of their action. Our findings suggest that the most active compounds provide a promising foundation for the continued development of new antimycobacterial agents.
This study unveils the single and combined drought and heat impacts on the photosynthetic performance of
cv. Icatu and
cv. Conilon Clone 153 (CL153). Well-watered (WW) potted plants were gradually ...submitted to severe water deficit (SWD) along 20 days under adequate temperature (25/20°C, day/night), and thereafter exposed to a gradual temperature rise up to 42/30°C, followed by a 14-day water and temperature recovery. Single drought affected all gas exchanges (including
) and most fluorescence parameters in both genotypes. However, Icatu maintained
and RuBisCO activity, and reinforced electron transport rates, carrier contents, and proton gradient regulation (PGR5) and chloroplast NADH dehydrogenase-like (NDH) complex proteins abundance. This suggested negligible non-stomatal limitations of photosynthesis that were accompanied by a triggering of protective cyclic electron transport (CEF) involving both photosystems (PSs). These findings contrasted with declines in RuBisCO and PSs activities, and cytochromes (
,
,
) contents in CL153. Remarkable heat tolerance in potential photosynthetic functioning was detected in WW plants of both genotypes (up to 37/28°C or 39/30°C), likely associated with CEF in Icatu. Yet, at 42/30°C the tolerance limit was exceeded. Reduced
and increased
values reflected non-stomatal limitations of photosynthesis, agreeing with impairments in energy capture (
rise), PSII photochemical efficiency, and RuBisCO and Ru5PK activities. In contrast to PSs activities and electron carrier contents, enzyme activities were highly heat sensitive. Until 37/28°C, stresses interaction was largely absent, and drought played the major role in constraining photosynthesis functioning. Harsher conditions (SWD, 42/30°C) exacerbated impairments to PSs, enzymes, and electron carriers, but uncontrolled energy dissipation was mitigated by photoprotective mechanisms. Most parameters recovered fully between 4 and 14 days after stress relief in both genotypes, although some aftereffects persisted in SWD plants. Icatu was more drought tolerant, with WW and SWD plants usually showing a faster and/or greater recovery than CL153. Heat affected both genotypes mostly at 42/30°C, especially in SWD and Icatu plants. Overall, photochemical components were highly tolerant to heat and to stress interaction in contrast to enzymes that deserve special attention by breeding programs to increase coffee sustainability in climate change scenarios.
One interesting approach to fight tuberculosis is the use of prodrugs that often have shown improved biological activities over drugs with poor absorption or difficulty to cross membranes. Previous ...studies demonstrate that weak acids such as benzoic acid, present antimycobacterial activity. Moreover, esters of those acids revealed to be a viable alternative since they may diffuse more easily through the cell membranes. Previously we showed that mycobacteria can easily activate benzoic acid esters by conversion to the corresponding acid. Since Zhang postulated that the activity of the acids can be dependent on their pKa, we set up to synthesize a library of benzoates with different electron withdrawing groups (4-chloro, 2,6-dichloro, 3,5-dichloro, 4-nitro, and 3,5 dinitro), to modulate pKa of the liberated acid and different alkoxy substituents (propyl, hexyl, and phenyl) to modulate their lipophilicity, and tested the activity of the esters and the corresponding free acids against mycobacteria. We also studied the activation of the esters by mycobacterial enzymes and the stability of the compounds in buffer and plasma. We concluded that all the benzoates in our study can be activated by mycobacterial enzymes and that the phenyl and hexyl esters presented higher activity than the corresponding free acids, with the nitrobenzoates, and especially the dinitrobenzoates, showing very interesting antitubercular activity that deserve further exploration. Our results did not show a correlation between the activity and the pKa of the acids.
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