Bathymetric origin shapes the physiological responses of Pterygophora californica (Laminariales, Phaeophyceae) to deep marine heatwaves.

Kelp communities are experiencing exacerbated heat-related impacts from more intense, frequent, and deeper marine heatwaves (MHWs), imperiling the long-term survival of kelp forests in the climate change scenario. The occurrence of deep thermal anomalies is of critical importance, as elevated temperatures can impact kelp populations across their entire bathymetric range. This study evaluates the impact of MHWs on mature sporophytes of Pterygophora californica (walking kelp) from the bathymetric extremes (8-10 vs. 25-27 m) of a population situated in Baja California (Mexico). The location is near the southernmost point of the species's broad distribution (from Alaska to Mexico). The study investigated the ecophysiological responses (e.g., photobiology, nitrate uptake, oxidative stress) and growth of adult sporophytes through a two-phase experiment: warming simulating a MHW and a post-MHW phase without warming. Generally, the effects of warming differed depending on the bathymetric origin of the sporophytes. The MHW facilitated essential metabolic functions of deep-water sporophytes, including photosynthesis, and promoted their growth. In contrast, shallow-water sporophytes displayed metabolic stress, reduced growth, and oxidative damage. Upon the cessation of warming, certain responses, such as a decline in nitrate uptake and net productivity, became evident in shallow-water sporophytes, implying a delay in heat-stress response. This indicates that variation in temperatures can result in more prominent effects than warming alone. The greater heat tolerance of sporophytes in deeper waters shows convincing evidence that deep portions of P. californica populations have the potential to serve as refuges from the harmful impacts of MHWs on shallow reefs.

Molecular imprinting technology and poly (ionic liquid)s: Promising tools with industrial application for the removal of acrylamide and furanic compounds from coffee and other foods.

Coffee is one of the most consumed beverages in the world. Coffee provides to the consumer special sensorial characteristics, can help to prevent diseases, improves physical performance and increases focus. In contrast, coffee consumption supplies a significant source of substances with carcinogenic and genotoxic potential such as furan, hydroxymethylfurfural (HMF), furfural (F), and acrylamide (AA). The present review addresses the issues around the presence of such toxic substances formed in Maillard reaction (MR) during thermal treatments in food processing, from chemical and, toxicological perspectives, occurrences in coffee and other foods processed by heating. In addition, current strategies advantages and disadvantages are presented along with application of molecular imprinting technology (MIT) and poly (ionic liquid) s (PIL) as an alternative to reduce the furan, HMF, F and AA content in coffee and other foods.

Virulence and Metabolism Crosstalk: Impaired Activity of the Type Three Secretion System (T3SS) in a Pseudomonas aeruginosa Crc-Defective Mutant.

Pseudomonas aeruginosa is a ubiquitous nosocomial opportunistic pathogen that harbors many virulence determinants. Part of P. aeruginosa success colonizing a variety of habitats resides in its metabolic robustness and plasticity, which are the basis of its capability of adaptation to different nutrient sources and ecological conditions, including the infected host. Given this situation, it is conceivable that P. aeruginosa virulence might be, at least in part, under metabolic control, in such a way that virulence determinants are produced just when needed. Indeed, it has been shown that the catabolite repression control protein Crc, which together with the RNA chaperon Hfq regulates the P. aeruginosa utilization of carbon sources at the post-transcriptional level, also regulates, directly or indirectly, virulence-related processes in P. aeruginosa. Among them, Crc regulates P. aeruginosa cytotoxicity, likely by modulating the activity of the Type III Secretion System (T3SS), which directly injects toxins into eukaryotic host cells. The present work shows that the lack of Crc produces a Type III Secretion-defective phenotype in P. aeruginosa. The observed impairment is a consequence of a reduced expression of the genes encoding the T3SS, together with an impaired secretion of the proteins involved. Our results support that the impaired T3SS activity of the crc defective mutant is, at least partly, a consequence of a defective protein export, probably due to a reduced proton motive force. This work provides new information about the complex regulation of the expression and the activity of the T3SS in P. aeruginosa. Our results highlight the need of a robust bacterial metabolism, which is defective in the ∆crc mutant, to elicit complex and energetically costly virulence strategies, as that provided by the T3SS.

Rural treatment of COVID-19 patients with pirfenidone, nitazoxanide and colchicine. Case series.

Combined treatments against SARS-CoV-2 are emerging and some have taken into account the post-COVID-19 fibrosis. The aim of this survey was to report the experience of treating COVID-19 patients with pirfenidone, nitazoxanide (NTZ) and colchicine. It was a case series report of COVID-19 patients treated from December 2020 to March 2021, in a rural health center located in the State of Mexico, Mexico. 23 patients were included (mean age 44.5 ± 17.1 years), 12 women (mean age 45.9 ± 17.9 years) and 11 men (mean age 43 ± 16.9 years) with four deaths (17.39%). The evolution time was of 17.3 ± 6.7 days being the main symptoms fever (82.6%), myalgia (69.6%) and cough (65.2%). The main comorbidities were overweight/obesity 18 (78.26%), type 2 diabetes mellitus (T2DM) 4 (17.39%), Chronic obstructive pulmonary disease (COPD) 5 (21.73%) and systemic hypertension 2 (8.69%). Two patients were intubated and both died; in these cases, they refused to take NTZ until after three days the medical doctor had prescribed it for the first time. It can be concluded that implementing a mixed treatment with pirfenidone, NTZ and colchicine could improve the survival rate in ambulatory patients of low socioeconomic status.

Understanding the Effect of Solvent Environment on the Interaction of Hydronium Ion with Biomass Derived Species: A Molecular Dynamics and Metadynamics Investigation.

The addition of aprotic solvents results in higher reactivities and selectivities in many key aqueous phase biomass reactions, including the acid-catalyzed conversion of fructose to 5-hydroxyl methyl furfural (HMF). The addition of certain co-solvents inhibits the formation of humins via preferential solvation of key functional groups and can alter reaction kinetics. An important factor in this context is the relative stability of the hydronium ion (the catalyst) in the vicinity of the biomass moiety as compared to that in bulk, as it could determine its efficacy in the protonation step. Hence, in the present work, molecular dynamics (MD) simulations of HMF (the model product) and fructose (the model reactant) in acidic water and water-DMSO mixtures are performed to analyze their interaction with the hydronium ions. We show that the presence of DMSO favors the interaction of the hydronium ion with fructose, whereas it has a detrimental effect on the interaction of hydronium ion with HMF. Well-tempered metadynamics (WT-MTD) simulations are performed to determine the relative stability of the hydronium ion in the immediate vicinity of fructose and HMF, as compared to that in the bulk solvent phase, as a function of solvent composition. We find that DMSO improves the stabilization of the hydronium ions in the first solvation shell of fructose compared to that in the bulk solvent. On the other hand, hydronium ions become less stable in the immediate vicinity of HMF, as the concentration of DMSO increases.

Antinociceptive Activity of Compounds from the Aqueous Extract of Melampodium divaricatum.

A decoction prepared from the aerial parts of Melampodium divaricatum showed antinociceptive and antihyperalgesic responses when tested in the formalin model in mice. From the CH2 Cl2 fraction of the decoction, two non-previously reported secondary metabolites, 3-O-ß-D-glucopyranosyl-16α-hydroxy-ent-kaurane (1) and melampodiamide (2) [(2'R*,4'Z)-2'-hydroxy-N-[(2S*,3S*,4R*)-1,3,4-trihydroxyoctadec-2-yl]tetracos-4-enamide] were separated and characterized by spectroscopic, spectrometric, and computational techniques. The flavonoids isoquercitrin and hyperoside, which possessed noted antinociceptive properties, were obtained from the active AcOEt fraction of the decoction. The chemical composition of the essential oil of the plant was also analyzed by gas chromatography-mass spectrometry. The major constituents were (E)-caryophyllene, germacrene D, ß-elemene, δ-elemene, γ-patchoulene, and 7-epi-α-selinene. Headspace solid-phase microextraction analysis detected (E)-caryophyllene as the main volatile compound of the plant.

An Assessment of Ambient Water Quality and Challenges with Access to Water and Sanitation Services for Individuals Experiencing Homelessness in Riverine Encampments.

Individuals experiencing unsheltered homelessness face significant barriers to accessing water, sanitation, and hygiene services, but the risks associated with this lack of access and barriers to service provision have been largely understudied. We analyzed water samples upstream and downstream of three homeless encampments in the San Diego River watershed and interviewed service providers from public and nonprofit sectors to assess local perceptions about challenges and potential solutions for water and sanitation service provision in this context. Water upstream from encampments contained detectable levels of caffeine and sucralose. Escherichia coli concentrations downstream of the encampments were significantly greater than concentrations upstream, but there was no significant change in the concentrations of other pollutants, including caffeine and sucralose. The HF183 marker of Bacteroides was only detected in one sample upstream of an encampment and was not detected downstream. Overall, there was insufficient evidence to suggest that the encampments studied here were responsible for contributing pollution to the river. Nevertheless, the presence of caffeine, sucralose, and HF183 indicated that there are anthropogenic sources of contamination in the river during dry weather and potential risks associated with the use of this water by encampment residents. Interviews with service providers revealed perceptions that the provision of water and sanitation services for this population would be prohibitively expensive. Interviewees also reported perceptions that most riverbank residents avoided contact with service providers, which may present challenges for the provision of water and sanitation service unless trust is first built between service providers and residents of riverine encampments.

Congenital malaria by Plasmodium falciparum. / Malaria congénita por Plasmodium falciparum.

Introdution: Congenital malaria (CM) is a Plasmodium spp infection acquired in utero or during delivery with nonspecific clinical manifestations. Plasmodium falciparum can cause severe illness in pregnant wo men and newborns. OBJECTIVE: to describe two cases of CM caused by Plasmodium falciparum, di fferential diagnosis of sepsis in newborns of pregnant women who live in or have visited endemic malaria zones. CLINICAL CASES: Female neonates born in a non-endemic malaria area, diagnosed with neonatal sepsis and treated with antibiotics without clinical response. After the first week of life, the peripheral blood smear identified trophozoites of Plasmodium falciparum thus the newborns were treated with intravenous quinine, improving their condition. The mothers of the two newborns who had malaria in pregnancy, one of them received treatment and she was asymptomatic, and the other one had severe malaria at the time of delivery. CONCLUSIONS: CM can cause severe neonatal disease with non-specific, sepsis-like clinical manifestations in which early treatment decreases the risk of complicated malaria. It is a differential diagnosis in newborns of women with a history of malaria during pregnancy or pregnant women visiting or living in endemic malaria areas.

Enrichment of ATP Binding Proteins Unveils Proteomic Alterations in Human Macrophage Cell Death, Inflammatory Response, and Protein Synthesis after Interaction with Candida albicans.

Macrophages are involved in the primary human response to Candida albicans. After pathogen recognition, signaling pathways are activated, leading to the production of cytokines, chemokines, and antimicrobial peptides. ATP binding proteins are crucial for this regulation. Here, a quantitative proteomic and phosphoproteomic approach was carried out for the study of human macrophage ATP-binding proteins after interaction with C. albicans. From a total of 547 nonredundant quantified proteins, 137 were ATP binding proteins and 59 were detected as differentially abundant. From the differentially abundant ATP-binding proteins, 6 were kinases (MAP2K2, SYK, STK3, MAP3K2, NDKA, and SRPK1), most of them involved in signaling pathways. Furthermore, 85 phosphopeptides were quantified. Macrophage proteomic alterations including an increase of protein synthesis with a consistent decrease in proteolysis were observed. Besides, macrophages showed changes in proteins of endosomal trafficking together with mitochondrial proteins, including some involved in the response to oxidative stress. Regarding cell death mechanisms, an increase of antiapoptotic over pro-apoptotic signals is suggested. Furthermore, a high pro-inflammatory response was detected, together with no upregulation of key mi-RNAs involved in the negative feedback of this response. These findings illustrate a strategy to deepen the knowledge of the complex interactions between the host and the clinically important pathogen C. albicans.

Correlation of Vitamin D with Inflammatory Cytokines, Atherosclerotic Parameters, and Lifestyle Factors in the Setting of Heart Failure: A 12-Month Follow-Up Study.

Vitamin D deficiency is highly prevalent worldwide. It has been associated with heart failure (HF) given its immunoregulatory functions. In-vitro and animal models have shown protective roles through mechanisms involving procollagen-1, JNK2, calcineurin/NFAT, NF-κB, MAPK, Th1, Th2, Th17, cytokines, cholesterol-efflux, oxLDL, and GLUT4, among others. A 12-month follow-up in HF patients showed a high prevalence of vitamin D deficiency, with no seasonal variation (64.7-82.4%). A positive correlation between serum 25(OH)D concentration and dietary intake of vitamin D-rich foods was found. A significant inverse correlation with IL-1ß (R = -0.78), TNF-α (R = -0.53), IL-6 (R = -0.42), IL-8 (R = -0.41), IL-17A (R = -0.31), LDL-cholesterol (R = -0.51), Apo-B (R = -0.57), total-cholesterol (R = -0.48), and triglycerides (R = -0.32) was shown. Cluster analysis demonstrated that patients from cluster three, with the lowest 25(OH)D levels, presented the lowermost vitamin D intake, IL-10 (1.0 ± 0.9 pg/mL), and IL-12p70 (0.5 ± 0.4 pg/mL), but the highest TNF-α (9.1 ± 3.5 pg/mL), IL-8 (55.6 ± 117.1 pg/mL), IL-17A (3.5 ± 2.0 pg/mL), total-cholesterol (193.9 ± 61.4 mg/dL), LDL-cholesterol (127.7 ± 58.2 mg/dL), and Apo-B (101.4 ± 33.4 mg/dL) levels, compared with patients from cluster one. Although the role of vitamin D in the pathogenesis of HF in humans is still uncertain, we applied the molecular mechanisms of in-vitro and animal models to explain our findings. Vitamin D deficiency might contribute to inflammation, remodeling, fibrosis, and atherosclerosis in patients with HF.

Differential item functioning by language on the PROMIS® physical functioning items for children and adolescents.

PURPOSE: To assess the equivalence of self-reports of physical functioning between pediatric respondents to the English- and Spanish-language patient-reported outcomes measurement information system (PROMIS®) physical functioning item banks. METHODS: The PROMIS pediatric physical functioning item banks include 29 upper extremity items and 23 mobility items. A sample of 5091 children and adolescents (mean age = 12 years, range 8-17; 49% male) completed the English-language version of the items. A sample of 605 children and adolescents (mean age = 12 years, range 8-17; 55% male; 96% Hispanic) completed the Spanish-language version of the items. RESULTS: We found language (English versus Spanish) differential item functioning (DIF) for 4 upper extremity items and 7 mobility items. Product-moment correlations between estimated upper extremity and mobility scores using the English versus the equated Spanish item parameters for Spanish-language respondents were 0.98 and 0.99, respectively. After excluding cases with significant person misfit, we found DIF for the same 4 upper extremity items that had DIF in the full sample and for 12 mobility items (including the same 7 mobility items that had DIF in the full sample). The identification of DIF items between English- and Spanish-language respondents was affected slightly by excluding respondents displaying person misfit. CONCLUSIONS: The results of this study provide support for measurement equivalence of self-reports of physical functioning by children and adolescents who completed the English- and Spanish-language surveys. Future analyses are needed to replicate the results of this study in other samples.

[¿Azitromicina como tratamiento contra Chlamydia trachomatis?]

Azithromycin and doxycycline effectiveness has been demonstrated in the treatment of urogenital chlamydiasis, which has remained unchanged for a long time. Autoinoculation has been proposed as a method of reinfection and persistence of the disease in women and probably also owing to azithromycin pharmacokinetics in this tissue. With the new diagnostic methods and tests of cure, a difference has been demonstrated in favor of doxycycline in the treatment of rectal chlamydiasis Antimicrobial resistance has not played a relevant role since no treatment-resistant strains have been found in vivo. Nevertheless, azithromycin remains a first-choice drug, since it can be administered as a single dose, which favors therapeutic adherence.

Se ha demostrado la efectividad de la azitromicina y la doxiciclina en el tratamiento de la clamidiasis urogenital, lo que se ha mantenido sin cambios por mucho tiempo. Se ha propuesto la autoinoculación como método de reinfección y persistencia de la enfermedad en las mujeres y también debido a la farmacocinética de la azitromicina en este tejido. Con los nuevos métodos diagnósticos y las pruebas de curación se ha comprobado una diferencia a favor de la doxiciclina en el tratamiento de la clamidiasis rectal. La resistencia antimicrobiana no ha desempeñado un papel relevante porque no se han encontrado cepas resistentes in vivo al tratamiento. A pesar de ello, la azitromicina sigue siendo un fármaco de primera elección ya que puede administrarse como una dosis única, lo que favorece el apego terapéutico.

Candida albicans Modifies the Protein Composition and Size Distribution of THP-1 Macrophage-Derived Extracellular Vesicles.

The effectiveness of macrophages in the response to systemic candidiasis is crucial to an effective clearance of the pathogen. The secretion of proteins, mRNAs, noncoding RNAs and lipids through extracellular vesicles (EVs) is one of the mechanisms of communication between immune cells. EVs change their cargo to mediate different responses, and may play a role in the response against infections. Thus we have undertaken the first quantitative proteomic analysis on the protein composition of THP-1 macrophage-derived EVs during the interaction with Candida albicans. This study revealed changes in EVs sizes and in protein composition, and allowed the identification and quantification of 717 proteins. Of them, 133 proteins changed their abundance due to the interaction. The differentially abundant proteins were involved in functions relating to immune response, signaling, or cytoskeletal reorganization. THP-1-derived EVs, both from control and from Candida-infected macrophages, had similar effector functions on other THP-1-differenciated macrophages, activating ERK and p38 kinases, and increasing both the secretion of proinflammatory cytokines and the candidacidal activity; while in THP-1 nondifferenciated monocytes, only EVs from infected macrophages increased significantly the TNF-α secretion. Our findings provide new information on the role of macrophage-derived EVs in response to C. albicans infection and in macrophages communication.

Multidrug efflux pumps as main players in intrinsic and acquired resistance to antimicrobials.

Multidrug efflux pumps constitute a group of transporters that are ubiquitously found in any organism. In addition to other functions with relevance for the cell physiology, efflux pumps contribute to the resistance to compounds used for treating different diseases, including resistance to anticancer drugs, antibiotics or antifungal compounds. In the case of antimicrobials, efflux pumps are major players in both intrinsic and acquired resistance to drugs currently in use for the treatment of infectious diseases. One important aspect not fully explored of efflux pumps consists on the identification of effectors able to induce their expression. Indeed, whereas the analysis of clinical isolates have shown that mutants overexpressing these resistance elements are frequently found, less is known on the conditions that may trigger expression of efflux pumps, hence leading to transient induction of resistance in vivo, a situation that is barely detectable using classical susceptibility tests. In the current article we review the structure and mechanisms of regulation of the expression of bacterial and fungal efflux pumps, with a particular focus in those for which a role in clinically relevant resistance has been reported.

Seasonal Variation in Vitamin D in Association with Age, Inflammatory Cytokines, Anthropometric Parameters, and Lifestyle Factors in Older Adults.

Vitamin D deficiency is present even in sunny regions. Ageing decreases pre-vitamin D production in the skin and is associated with altered cytokine profile. We performed a multivariate analysis considering lifestyle factors, anthropometric, and inflammatory markers according to seasonal variation in Mexican healthy older adults. The same cohort was followed during 12 months. Vitamin D deficiency/insufficiency was found in 91.3% of the subjects despite living in appropriate latitude (25°40'0″N). 25(OH)D levels remained below <30 ng/mL through all seasons. Vitamin D deficiency did not correlate to sun exposure or dietary intake. Gender was the strongest associated factor, explaining a variance of 20%. Waist circumference (WC) greater than 88 cm was a risk factor for vitamin D deficiency. Age (>74 years) combined with WC (>88 cm) and BMI (>32.7) showed a high probability (90%) of vitamin D deficiency. Remarkably, an increase in one centimeter in WC decreased 25(OH)D by 0.176 ng/mL, while an increase in one point BMI decreased 25(OH)D by 0.534 ng/mL. A cutoff point of 74 years of age determined probability of vitamin D hipovitaminosis. Vitamin D deficiency was correlated with TNF-α serum levels, possibly increasing the susceptibility of older adults to a proinflammatory state and its related diseases.

Capacity of milk composition to identify the feeding system used to feed dairy cows.

This Research Paper addresses the hypothesis that is possible to identify the type of feed used for dairy cows by means of the analysis of milk composition and the fatty acid profile of milk fat. Sixteen dairy farms were monitored during 1 year with quarterly visits between summer 2014 and spring 2015. Rations varied throughout the year due to annual dynamic change of forage production, forage rotation, variation of nutrient requirements according to physiological state of the animal, etc. The ingredients of the rations were analysed by cluster identifying five feeding systems based on the main ingredient of the diet: grazing, maize silage, grass silage, dry forage and concentrate. Milk composition could explain up to 91·3% of the total variability among feeding systems, while fatty acid profile could explain only up to 61·2% of total variability. However, when the sum of types of fatty acids and their ratios are taken, up to 93·5% of total variability could be explained. The maize silage system had the greatest milk yield, protein, solid non-fat and urea proportions, as well as the highest proportion of saturated fatty acid and lowest concentration of trans11 18 : 1, cis9 18 : 1 and 18 : 3 n3. Principal component analysis distinguishes the maize silage system from other feeding systems, both from milk composition and milk fatty acid profile. Concentrate system overlapped partially with the grazing, grass silage and dry forage systems. The latter systems had the highest concentrations of cis9 18 : 1, trans11 18 : 1 and 18 : 3, but there was no clear differentiation among them.

Patients' perceptions of argentine physicians' empathy based on the jefferson scale of patient's perceptions of physician empathy: Psychometric data and demographic differences.

BACKGROUND: The aim of this study was to evaluate the validity of a modified Spanish version of the Jefferson Scale of Patient's Perceptions of Physician Empathy (JSPPPE) in Argentine patients and to explore how local demographic characteristics influence patients' perceptions of their physicians' empathy. METHODS: A survey was conducted in March 2013 among 400 Spanish-speaking outpatients attending three different public or private hospitals of Buenos Aires. A principal component analysis (PCA) was used to identify the JSPPPE factor structure, and a confirmatory factor analysis (CFA) was employed to evaluate its construct validity. Demographic variables including age, gender, geographic origin, education, health coverage, regular physician-established and patient-perceived health status were used to find what factors may influence empathy rating. RESULTS: The PCA yielded a one-factor model that accounted for 77.5% of the variance, and an adequate model fit was observed with CFA indices. Male and elderly patients, South American descendants, less educated people, and public hospital attendants were associated with a higher JSPPPE score. Patients perceived a lower interest of physicians in their daily problems and a poorer capacity "to stand in their shoes." DISCUSSION: The JSPPPE provides a valid score to measure patients' perceptions of physician empathy in Argentina. These findings afford insight into Argentine patients' awareness of their doctors' empathic concern; however, JSPPPE scores may be alternatively interpreted in terms of patients' satisfaction or likeability.

Apoptosis of Candida albicans during the Interaction with Murine Macrophages: Proteomics and Cell-Death Marker Monitoring.

Macrophages may induce fungal apoptosis to fight against C. albicans, as previously hypothesized by our group. To confirm this hypothesis, we analyzed proteins from C. albicans cells after 3 h of interaction with macrophages using two quantitative proteomic approaches. A total of 51 and 97 proteins were identified as differentially expressed by DIGE and iTRAQ, respectively. The proteins identified and quantified were different, with only seven in common, but classified in the same functional categories. The analyses of their functions indicated that an increase in the metabolism of amino acids and purine nucleotides were taking place, while the glycolysis and translation levels dropped after 3 h of interaction. Also, the response to oxidative stress and protein translation were reduced. In addition, seven substrates of metacaspase (Mca1) were identified (Cdc48, Fba1, Gpm1, Pmm1, Rct1, Ssb1, and Tal1) as decreased in abundance, plus 12 proteins previously described as related to apoptosis. Besides, the monitoring of apoptotic markers along 24 h of interaction (caspase-like activity, TUNEL assay, and the measurement of ROS and cell examination by transmission electron microscopy) revealed that apoptotic processes took place for 30% of the fungal cells, thus supporting the proteomic results and the hypothesis of macrophages killing C. albicans by apoptosis.