Genomic Characterization of Two NDM-5-Producing Isolates of Klebsiella pneumoniae ST11 from a Single Patient.

Two metallo-ß-lactamase-producing Klebsiella pneumoniae (HA30 and HA31) were isolated in a hospital in Argentina during 2018. K. pneumoniae HA30 was isolated from a rectal swab during the epidemiological surveillance for carbapenemase-producing strains, while K. pneumoniae HA31 was collected from the same patient 4 days after hospitalization. The aim of the present study was to identify the clonal relationships and resistome of these two NDM-producing K. pneumoniae strains isolated from a patient with a fatal outcome. Whole-genome sequencing (WGS) was performed using Illumina MiSeq-I, and subsequent analysis involved genome assembly, annotation, antibiotic resistance gene identification, multilocus sequence typing (MLST), and plasmid characterization using bioinformatics tools. Conjugation assays to E. coli J53 was conducted as previously described. K. pneumoniae HA30 exhibited extensively drug-resistant phenotype, while HA31 was multidrug-resistant as defined by Magiorakos et al., including both resistance to carbapenems, aminoglycosides and ciprofloxacin with blaNDM-5, blaCTX-M-15 and rmtB genes found in both strains. MLST analysis showed that both strains belonged to ST11, differing by only 4 cgSNPs, indicating that K. pneumoniae HA30 and HA31 were the same strain. Conjugation assays revealed that K. pneumoniae HA31 strain possessed a transferable plasmid to E. coli J53. Bioinformatics studies identified that the same strain colonizing an inpatient during hospital admission subsequently caused the infection leading to a fatal outcome, being the first report of blaNDM-5, rmtB and blaCTX-M-15 genes in a K. pneumoniae ST11 strain from Latin America. Our results also highlighted the importance of focusing on epidemiological surveillance programs.

Structure optimization of lipopeptide assemblies for aldol reactions in an aqueous medium.

Four amphiphilic peptides were synthesized, characterized, and evaluated regarding their efficiency in the catalysis of direct aldol reactions in water. The lipopeptides differ by having a double lipid chain and a guanidinium pyrrole group functionalizing one Lys side chain. All the samples are composed of the amino acids l-proline (P), l-arginine (R), or l-lysine (K) functionalized with the cationic guanidiniocarbonyl pyrrole unit (GCP), l-tryptophan (W), and l-glycine (G), covalently linked to one or two long aliphatic chains, leading to surfactant-like designs with controlled proline protonation state and different stereoselectivity. Critical aggregation concentrations (cac) were higher in the presence of the GCP group, suggesting that self-assembly depends on charge distribution along the peptide backbone. Cryogenic Transmission Electron Microscopy (Cryo-TEM) and Small Angle X-ray Scattering (SAXS) showed a rich polymorphism including spherical, cylindrical, and bilayer structures. Molecular dynamics simulations performed to assess the lipopeptide polymorphs revealed an excellent agreement with core-shell arrangements derived from SAXS data and provided an atomistic view of the changes incurred by modifying head groups and lipid chains. The resulting nanostructures behaved as excellent catalysts for aldol condensation reactions, in which superior conversions (>99%), high diastereoselectivities (ds = 94 : 6), and enantioselectivities (ee = 92%) were obtained. Our findings contribute to elucidate the effect of nanoscale organization of lipopeptide assemblies in the catalysis of aldol reactions in an aqueous environment.

Implementation of a Diabetes Self-Management Education and Support Intervention in Rural Guatemala: A Mixed-Methods Evaluation Using the RE-AIM Framework.

INTRODUCTION: To address the global diabetes epidemic, lifestyle counseling on diet, physical activity, and weight loss is essential. This study assessed the implementation of a diabetes self-management education and support (DSMES) intervention using a mixed-methods evaluation framework. METHODS: We implemented a culturally adapted, home-based DSMES intervention in rural Indigenous Maya towns in Guatemala from 2018 through 2020. We used a pretest-posttest design and a mixed-methods evaluation approach guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Quantitative data included baseline characteristics, implementation metrics, effectiveness outcomes, and costs. Qualitative data consisted of semistructured interviews with 3 groups of stakeholders. RESULTS: Of 738 participants screened, 627 participants were enrolled, and 478 participants completed the study. Adjusted mean change in glycated hemoglobin A1c was -0.4% (95% CI, -0.6% to -0.3%; P < .001), change in systolic blood pressure was -5.0 mm Hg (95% CI, -6.4 to -3.7 mm Hg; P < .001), change in diastolic blood pressure was -2.6 mm Hg (95% CI, -3.4 to -1.9 mm Hg; P < .001), and change in body mass index was 0.5 (95% CI, 0.3 to 0.6; P < .001). We observed improvements in diabetes knowledge, distress, and most self-care activities. Key implementation factors included 1) recruitment barriers for men, 2) importance of patient-centered care, 3) role of research staff in catalyzing health worker involvement, 4) tradeoffs between home and telephone visits, and 5) sustainability challenges. CONCLUSION: A community health worker-led DSMES intervention was successfully implemented in the public health system in rural Guatemala and resulted in significant improvements in most clinical and psychometric outcomes. Scaling up sustainable DSMES in health systems in rural settings requires careful consideration of local barriers and facilitators.

Viral Infection Drives the Regulation of Feeding Behavior Related Genes in Salmo salar.

The feeding behavior in fish is a complex activity that relies on the ability of the brain to integrate multiple signals to produce appropriate responses in terms of food intake, energy expenditure, and metabolic activity. Upon stress cues including viral infection or mediators such as the proinflammatory cytokines, prostaglandins, and cortisol, both Pomc and Npy/Agrp neurons from the hypothalamus are stimulated, thus triggering a response that controls both energy storage and expenditure. However, how appetite modulators or neuro-immune cues link pathogenesis and energy homeostasis in fish remains poorly understood. Here, we provide the first evidence of a molecular linkage between inflammation and food intake in Salmon salar. We show that in vivo viral challenge with infectious pancreatic necrosis virus (IPNV) impacts food consumption by activating anorexic genes such as mc4r, crf, and pomcb and 5-HT in the brain of S. salar. At the molecular level, viral infection induces an overall reduction in lipid content in the liver, favoring the production of AA and EPA associated with the increment of elovl2 gene. In addition, infection upregulates leptin signaling and inhibits insulin signaling. These changes are accompanied by a robust inflammatory response represented by the increment of Il-1b, Il-6, Tnfa, and Pge2 as well as an increased cortisol level in vivo. Thus, we propose a model in which hypothalamic neurons respond to inflammatory cytokines and stress-related molecules and interact with appetite induction/inhibition. These findings provide evidence of crosstalk between pathogenesis-driven inflammation and hypothalamic-pituitary-adrenocortical axes in stress-induced food intake behavior in fish.

Behavioural Fever Promotes an Inflammatory Reflex Circuit in Ectotherms.

BACKGROUND: The communication between the brain and the immune system is a cornerstone in animal physiology. This interaction is mediated by immune factors acting in both health and pathogenesis, but it is unclear how these systems molecularly and mechanistically communicate under changing environmental conditions. Behavioural fever is a well-conserved immune response that promotes dramatic changes in gene expression patterns during ectotherms' thermoregulatory adaptation, including those orchestrating inflammation. However, the molecular regulators activating the inflammatory reflex in ectotherms remain unidentified. METHODS: We revisited behavioural fever by providing groups of fish a thermal gradient environment during infection. Our novel experimental setup created temperature ranges in which fish freely moved between different thermal gradients: (1) wide thermoregulatory range; T° = 6.4 °C; and (2) restricted thermoregulatory range; T° = 1.4 °C. The fish behaviour was investigated during 5-days post-viral infection. Blood, spleen, and brain samples were collected to determine plasmatic pro- and anti-inflammatory cytokine levels. To characterize genes' functioning during behavioural fever, we performed a transcriptomic profiling of the fish spleen. We also measured the activity of neurotransmitters such as norepinephrine and acetylcholine in brain and peripheral tissues. RESULTS: We describe the first set of the neural components that control inflammatory modulation during behavioural fever. We identified a neuro-immune crosstalk as a potential mechanism promoting the fine regulation of inflammation. The development of behavioural fever upon viral infection triggers a robust inflammatory response in vivo, establishing an activation threshold after infection in several organs, including the brain. Thus, temperature shifts strongly impact on neural tissue, specifically on the inflammatory reflex network activation. At the molecular level, behavioural fever causes a significant increase in cholinergic neurotransmitters and their receptors' activity and key anti-inflammatory factors such as cytokine Il10 and Tgfß in target tissues. CONCLUSION: These results reveal a cholinergic neuronal-based mechanism underlying anti-inflammatory responses under induced fever. We performed the first molecular characterization of the behavioural fever response and inflammatory reflex activation in mobile ectotherms, identifying the role of key regulators of these processes. These findings provide genetic entry points for functional studies of the neural-immune adaptation to infection and its protective relevance in ectotherm organisms.

Prevalence of mental disorder and impact on quality of life in inflammatory bowel disease.

INTRODUCTION: Different studies have described psychiatric comorbidities in inflammatory bowel disease (IBD) patients, but most of them focus mainly on depression and anxiety. Even though major mental disorders are considered one of the main factors that decrease quality of life (QoL), its role in IBD patients remains unclear. We sought to identify the prevalence of different mental disorders as well as its relationship with QoL. PATIENTS AND METHODS: Subjects were recruited from the IBD Clinic. IBD Questionnaire 32 and structured clinical interview (SCID) for DMS-IV Text Revision were applied. Demographic and clinical data were collected via self-report questionnaires and medical records. The correlation between mental disorders and QoL (IBDQ-32 score) was evaluated using the Spearman correlation test. RESULTS: In all, 104 patients were recruited, 12 with Crohn's disease, and 92 with ulcerative colitis. The prevalence of any major mental disorder was 56.7%: anxiety (44.2%), mood (27.9%), substance use (12.2%), and other psychiatric diagnoses (17.3%), and 29.8% of the patients presented three or more comorbid diagnoses. Mental Disorder (p=0.005), mood disorder (p=0.004), anxiety disorder (p=0.009), were found to be significantly associated with lower QoL. Substance use disorder was associated with lower Digestive QoL (p=0.01). Major depressive disorder (p=0.004), social phobia (p=0.03), PTSD (p=0.02), and Generalized Anxiety Disorder (p<0.001), were found to be significantly associated with lower QoL. CONCLUSIONS: IBD patients had important psychiatric comorbidity that significantly affects their QoL. These results warrant a systematic evaluation of psychiatric conditions in IBD patients.

Amyloid Peptide Mixtures: Self-Assembly, Hydrogelation, Nematic Ordering, and Catalysts in Aldol Reactions.

Morphological, spectroscopic, and scattering studies of the self-assembly and aggregation of mixtures of [RF]4 and P[RF]4 peptides (where R = arginine; F = phenylalanine; P = proline), in solution and as hydrogels, were performed to obtain information about polymorphism. CD data confirmed a ß-sheet secondary structure in aqueous solution, and TEM images revealed nanofibers with diameters of ∼10 nm and micrometer lengths. SAXS curves were fitted using a mass fractal-component and a long cylinder shell form factor for the liquid samples, and only a long cylinder shell form factor for the gels. Increasing the P[RF]4 content in the systems leads to a reduction in cylinder radius and core scattering density, suggesting an increase in packing of the peptide molecules; however, the opposite effect is observed for the gels, where the scattering density is higher in the shell for the systems containing higher P[RF]4 content. These compounds show potential as catalysts in the asymmetric aldol reactions, with cyclohexanone and p-nitrobenzaldehyde in aqueous media. A moderate conversion (36.9%) and a good stereoselectivity (69:31) were observed for the system containing only [RF]4. With increasing P[RF]4 content, a considerable decrease of the conversion was observed, suggesting differences in the self-assembly and packing factor. Rheological measurements were performed to determine the shear moduli for the soft gels.

Polymorphism of asymmetric catalysts based on amphiphilic lipopeptides in solution.

The self-assembly of model [P]RWG lipopeptides (P: l-proline, R: l-arginine, W: l-tryptophan, G: l-glycine), containing one or two aliphatic octadecyl (C18) chains in water and cyclohexanone/water solutions was examined. The self-assembly of mixtures of these RWG and PRWG lipopeptides was also investigated. These materials presented a similar critical aggregation concentration of ∼4.0 × 10-4 wt% and were characterized by unordered secondary structures with some ß-sheet content. TEM and cryo-TEM revealed the presence of mainly nanotape structures with micelles observed for systems rich in PRWG(C18H37). Analysis of detailed SAXS form factor measurements revealed the presence of bilayers 3-4 nm thick while the PRWG(C18H37) micelles have a core radius of approximately 3 nm, and a shell thickness of 2 nm. For the cyclohexanone/water systems polymorphs containing cluster aggregates (with radius of 0.25 nm to 0.50 nm) and some elongated structures (with radius of 5.7 nm to 26.1 nm) were seen. Longer structures were formed with the increase of the proline-containing lipopeptide content. The catalytic activity of these peptides was assessed using a model nitro-aldol reaction. The concentration of water in the reaction system influenced the conversion, higher content promoted better efficiency for the water systems, but the opposite was observed for the cyclohexanone/water samples.

Structure-activity relationship study of antitrypanosomal chalcone derivatives using multivariate analysis.

Chagas disease represents one of several neglected diseases with a reduced number of chemotherapeutical drugs including the highly toxic compounds benznidazole and nifurtimox. In this sense, natural products represent an import scaffold for the discovery of new biologically active compounds, in which chalcones are promising representatives due to their antitrypanosomal potential. In this work, a series of 36 chalcone derivatives were synthesized and tested against trypomastigotes of Trypanosoma cruzi. In addition, a detailed investigation on their molecular features was performed. The obtained results suggest that certain molecular features are fundamental for an efficient antitrypanosomal potential of chalcones, such as allylic groups, α,ß-unsaturated carbonyl system, and aromatic hydroxyl groups. These results were obtained based on the interpretation of machine-learning and multivariate statistical methods, which revealed the essential characteristics of chalcone prototypes against trypomastigotes of T. cruzi.

An interview with Rudolf Jaenisch.

Rudolf Jaenisch is a Professor of Biology at Massachusetts Institute of Technology, a founding member of the Whitehead Institute for Biomedical Research and the current president of the International Society for Stem Cell Research (ISSCR). His contributions to the stem cell field span from making the first transgenic mouse to seminal advances in the reprogramming field, and much more. In recognition of his pioneering research leading to induced pluripotency, he recently received the 2015 March of Dimes Prize in Developmental Biology. At the recent Keystone Meeting on 'Transcriptional and Epigenetic Influences on Stem Cell States' in Colorado, we had the opportunity to talk to him about his life and work.

The expression of TRPV channels, prostaglandin E2 and pro-inflammatory cytokines during behavioural fever in fish.

A fever, or increased body temperature, is a symptom of inflammation, which is a complex defence reaction of the organism to pathogenic infections. After pathogens enter the body, immune cells secrete a number of agents, the functions of which stimulate the body to develop a functional immune and fever response. In mammals it is known that PGE2 is the principal mediator of fever. The extent to which PGE2 and other pro-inflammatory cytokines such as TNF-α, IL-6, or IL-1ß could be involved in the induction of behavioural fever in fish remains to be clarified. Several members of the transient receptor potential (TRP) family of ion channels have been implicated as transducers of thermal stimuli, including TRPV1 and TRPV2, which are activated by heat. Here we show that members of the TRP family, TRPV1 and TRPV4, may participate in the coordination of temperature sensing during the behavioural fever. To examine the behavioral fever mechanism in Salmo salar an infection with IPNV, infectious pancreatic necrosis virus, was carried out by an immersion challenge with 10 × 105 PFU/mL-1 of IPNV. Behavioural fever impacted upon the expression levels of both TRPV1 and TRPV4 mRNAs after the viral challenge and revealed a juxtaposed regulation of TRPV channels. Our results suggest that an increase in the mRNA abundance of TRPV1 is tightly correlated with a significant elevation in the expression of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α and PGE2) in the Pre-Optic Area (POA) and cytokine release in plasma. Together, these data indicate that the reduction of TRPV4 expression during behavioural fever may contribute to the onset of behavioural fever influencing movement toward higher water temperatures. Our data also suggest an effect of TRPV channels in the regulation of behavioural fever through activation of EP3 receptors in the central nervous system by PGE2 induced by plasma-borne cytokines. These results highlight for first time in mobile ectotherms the key role of pro-inflammatory cytokines and TRPV channels in behavioural fever that likely involves a complex integration of prostaglandin induction, cytokine recognition and temperature sensing.

Hospital Anxiety and Depression Scale (HADS): Validation in Mexican Patients with Inflammatory Bowel Disease. / Escala de Ansiedad y Depresión Hospitalaria (HADS): Validación en pacientes mexicanos con enfermedad inflamatoria intestinal.

INTRODUCTION: The Hospital Anxiety and Depression Scale (HADS) is a self-administered instrument for outpatients, but its behaviour differs according to the clinical population to which it is applied. In Mexico it is not validated in patients with Inflammatory Bowel Disease (IBD). OBJECTIVES: To validate the HADS scale in the Mexican population with IBD. METHODS: 112 patients with IBD from the "Salvador Zubirán" National Institute of Medical Sciences and Nutrition were included, to whom the HADS was applied and some demographic and clinical characteristics of the disease were evaluated. An exploratory factor analysis was performed and factorial congruence was calculated to determine the construct validity of the HADS, while reliability was evaluated using Cronbach's alpha. RESULTS: The result of the varimax rotation of the 14 items of the HADS explained 50.1% of the variance, having two main factors. Ten items showed high factor loading for the dimensions originally proposed. The internal consistency of the HADS was high (alpha=0.88) with high values for the congruence coefficients. CONCLUSIONS: The HADS scale is a valid instrument to detect possible cases of Anxiety and Depression in Mexican patients with IBD. The validation of this instrument allows its routine use for the integral evaluation of the patient and their timely referral to mental health.

[Analysis of human cyst echinococcosis in a northern Chilean region from 2008 to 2012]. / Análisis de la hidatidosis humana en la Región de Coquimbo entre los años 2008 y 2012.

BACKGROUND: The Coquimbo Region in Chile has the highest incidence of hydatidosis in central and northern Chile. AIM: To analyze the incidence of human cystic echinococcosis (CE) in the Coquimbo Region between 2008 and 2012. MATERIAL AND METHODS: Official records of reported cases were analyzed. The association of the location, age and sex with the presence/absence of CE was analyzed by means of logistic regressions. The incidence was reported as cases per 100,000 inhabitants. RESULTS: The mean annual incidence was 2.6 cases per 100,000 inhabitants, which ranged from 3.1 (2010) to 1.9 (2012) cases. The districts with higher incidence were Punitaqui (21.2 cases), Paihuano (9 cases), Rio Hurtado (8 cases), Canela (8.1 cases), Monte Patria (7.9 cases), Vicuña (6.9 cases) and Combarbalá (6.9 cases). The incidence in these locations was significantly higher than elsewhere in the region. Males had a significantly higher incidence than females (3.3 and 1.8 respectively). Incidence increased significantly with age, notably increasing after 45 years of age. CONCLUSIONS: Rural locations had the highest incidences of CE in the Coquimbo Region. The disease was reported more commonly in adults and mainly in men.

Frequency, Clinical Features and Factors Associated with Pouchitis after Proctocolectomy with Ileo-Pouch-Anal Anastomosis in Patients with Ulcerative Colitis: A Latin-American Country Retrospective-Cohort Study.

BACKGROUND: Pouchitis is the most common complication of proctocolectomy with ileo-pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). No previous study in Mexico has evaluated this issue; our aim was to evaluate its frequency, clinical characteristics and factors associated with its presence in Mexican patients with UC and IPAA. METHODS: Retrospective-cohort study including 70 patients with histopathological diagnosis of UC and IPAA between 1983 and 2014 from inflammatory bowel disease clinic of a tertiary care center. The statistical analysis used descriptive statistics, chi-square and Fisher's exact test for categorical variables and Student's t test for numeric variables. Univariate analysis was performed to identify the factors associated. RESULTS: Patients presenting with pouchitis accounted for 48.6%. From the 34 cases, 12 (35.3%) had inactive pouchitis; 7 (20.6%) active acute pouchitis; 15 (44.1%) chronic active pouchitis. On average, pouchitis occurred 5.37 years after IPPA. Factors probably associated with its occurrence were the presence of autoimmune concomitant diseases (ACDs; p = 0.06, OR 4.40, 95% CI 0.84-22.9) and extra-intestinal manifestations (EIMs; p = 0.05, OR 2.53, 95% CI 0.96-6.64), which was also probably associated with chronic active pouchitis (p = 0.06, OR 0.31, 95% CI 0.07-1.31). CONCLUSIONS: The frequency of pouchitis is high in Mexican UC patients after IPAA. ACDs and EIMs were probably associated with its development.

Structure of the α-tubulin acetyltransferase, αTAT1, and implications for tubulin-specific acetylation.

Protein acetylation is an important posttranslational modification with the recent identification of new substrates and enzymes, new links to disease, and modulators of protein acetylation for therapy. α-Tubulin acetyltransferase (αTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes. Here, we present the X-ray crystal structure of the human αTAT1/acetyl-CoA complex. Together with structure-based mutagenesis, enzymatic analysis, and functional studies in cells, we elucidate the catalytic mechanism and mode of tubulin-specific acetylation. We find that αTAT1 has an overall fold similar to the Gcn5 histone acetyltransferase but contains a relatively wide substrate binding groove and unique structural elements that play important roles in α-tubulin-specific acetylation. Conserved aspartic acid and cysteine residues play important catalytic roles through a ternary complex mechanism. αTAT1 mutations have analogous effects on tubulin acetylation in vitro and in cells, demonstrating that it is the central determining factor of α-tubulin K40 acetylation levels in vivo. Together, these studies provide general insights into distinguishing features between histone and tubulin acetyltransferases, and they have specific implications for understanding the molecular basis of tubulin acetylation and for developing small molecule modulators of microtubule acetylation for therapy.

Analysis of human samples reveals impaired SHH-dependent cerebellar development in Joubert syndrome/Meckel syndrome.

Joubert syndrome (JS) and Meckel syndrome (MKS) are pleiotropic ciliopathies characterized by severe defects of the cerebellar vermis, ranging from hypoplasia to aplasia. Interestingly, ciliary conditional mutant mice have a hypoplastic cerebellum in which the proliferation of cerebellar granule cell progenitors (GCPs) in response to Sonic hedgehog (SHH) is severely reduced. This suggests that Shh signaling defects could contribute to the vermis hypoplasia observed in the human syndromes. As existing JS/MKS mutant mouse models suggest apparently contradictory hypotheses on JS/MKS etiology, we investigated Shh signaling directly on human fetal samples. First, in an examination of human cerebellar development, we linked the rates of GCP proliferation to the different levels and localizations of active Shh signaling and showed that the GCP possessed a primary cilium with CEP290 at its base. Second, we found that the proliferation of GCPs and their response to SHH were severely impaired in the cerebellum of subjects with JS/MKS and Jeune syndrome. Finally, we showed that the defect in GCP proliferation was similar in the cerebellar vermis and hemispheres in all patients with ciliopathy analyzed, suggesting that the specific cause of vermal hypo-/aplasia precedes this defect. Our results, obtained from the analysis of human samples, show that the hemispheres and the vermis are affected in JS/MKS and provide evidence of a defective cellular mechanism in these pathologic processes.

Intrinsic and environmental modulation of stereoselective aldol organocatalyzed reactions by proline-containing lipopeptides.

Proline, along with its derivatives, has been employed as an efficient organocatalyst for aldol reactions, with the ability to promote the creation of stereoselective C-C bonds. Even though the Houk-List transition state model is able to explain the stereoselectivity observed when proline is used as a catalyst, few studies investigate the role of microheterogeneous media in modulating the reaction outcome. In this work, molecular dynamics and electronic structure calculations were used to investigate the aldol reaction in the condensed phase. Our research focused on a lipopeptide compound incorporating the proline residue within the sequence PRWG-(C18H37), where P represents l-proline, R stands for l-arginine, W for l-tryptophan, and G for l-glycine. This sequence is covalently bonded to a hydrophobic segment formed by a long aliphatic chain, acting as an organocatalyst in an aqueous solution. This catalytic phase utilizes the complex chemical environment of the solution to achieve high selectivity. Our findings indicate a Houk-List-like mechanism, in which the amide acts as an H-bond donor, complemented by a mechanism in which the counter ion, trifluoracetic acid (TFA), acts as a proton shuttle. Both mechanisms demonstrated low energy barriers-12.23 and 1.42 kcal mol-1 for the (S,R) stereoisomer formation, computed using DLPNO-CCSD with def2-TZVPP basis set. Further, to explore the catalytic effect of the PRWG-(C18H37) lipopeptide in water, molecular dynamics simulations were conducted. It was observed that the micellar phase significantly enhances stereospecific encounters, favouring the experimentally observed ratio of (SR/SS) isomers, in contrast to reactions in a pure cyclohexanone medium. By quantifying the effects enabled by the supramolecular assembly, we were able to shed light on the factors that modify and enhance the stereoslectivity of the reaction.

Relationship between skin-to-skin contact during the first hour of life and duration of exclusive breastfeeding.

BACKGROUND: Exclusive breastfeeding (BF) has the greatest potential impact on child mortality of any preventive intervention. Skin-to-skin contact (SSC) during the first hour of life is beneficial for initiating BF; however, routine separation of mother and infant is still common. This work aimed to demonstrate that SSC during the first hour of life is associated with a greater frequency and duration of exclusive BF. METHODS: This is an observational case-control study. We reviewed the medical records of patients born between 2016 and 2022 classified as cases or controls based on the history of SSC in the first hour of life. Statistical analysis was performed using SPSS version 28. RESULTS: We included 362 medical records, of which 200 (55.2%) had SSC and were considered cases; the 162 (44.8%) who did not have SSC were considered controls. Those who received SSC were more likely to receive exclusive BF at 3 (163 [81.5%] vs. 94 [58%], p < 0.001) and 6 months of age (147 [73.5%] vs. 83 [51.2%], p < 0.001). CONCLUSIONS: Patients who received SSC in the first hour of life were more likely to receive exclusive BF at 3 and 6 months of age. Promoting and respecting this practice is essential to increase the possibility of a newborn to be exclusively breastfed for the first 6 months of life.

INTRODUCCIÓN: La lactancia materna exclusiva (LME) es la intervención preventiva con mayor impacto en mortalidad infantil. El contacto piel con piel (CPP) durante la primera hora de vida es un periodo crítico para establecer la lactancia; sin embargo, la separación rutinaria del recién nacido de su madre es frecuente. El objetivo de este trabajo fue demostrar que el CPP durante la primera hora se asocia con mayor frecuencia y duración de LME. MÉTODOS: Se llevó a cabo un estudio observacional de casos y controles. Se revisaron expedientes de pacientes de nuestra consulta pediátrica que nacieron entre 2016 y 2022. Se clasificaron como casos y controles de acuerdo con el antecedente de haber recibido CPP durante la primera hora de vida. Se realizó el análisis estadístico en SPSS version 28. RESULTADOS: Se incluyeron 362 expedientes, de los cuales 200 (55.2%) recibieron CPP en la primera hora de vida y fueron considerados casos; los 162 (44.8%) que no lo hicieron fueron considerados controles. Aquellos que recibieron CPP tuvieron con mayor frecuencia LME a los 3 (163 [81.5%] vs. 94 [58%], p < 0.001) y 6 meses de edad (147 [73.5%] vs. 83 [51.2%], p < 0.001). CONCLUSIONES: La frecuencia con la cual los pacientes lograron tener lactancia materna exclusiva a los 3 y 6 meses es mayor en aquellos en los que se respeta el CPP en la primera hora de vida. Promover y respetar esta práctica es fundamental para incrementar las probabilidades de que los lactantes reciban LME durante sus primeros 6 meses de vida.

Sporadic clone Escherichia coli ST615 as a vector and reservoir for dissemination of crucial antimicrobial resistance genes.

There is scarce information concerning the role of sporadic clones in the dissemination of antimicrobial resistance genes (ARGs) within the nosocomial niche. We confirmed that the clinical Escherichia coli M19736 ST615 strain, one of the first isolates of Latin America that harbors a plasmid with an mcr-1 gene, could receive crucial ARG by transformation and conjugation using as donors critical plasmids that harbor bla CTX-M-15, bla KPC-2, bla NDM-5, bla NDM-1, or aadB genes. Escherichia coli M19736 acquired bla CTX-M-15, bla KPC-2, bla NDM-5, bla NDM-1, and aadB genes, being only blaNDM-1 maintained at 100% on the 10th day of subculture. In addition, when the evolved MDR-E. coli M19736 acquired sequentially bla CTX-M-15 and bla NDM-1 genes, the maintenance pattern of the plasmids changed. In addition, when the evolved XDR-E. coli M19736 acquired in an ulterior step the paadB plasmid, a different pattern of the plasmid's maintenance was found. Interestingly, the evolved E. coli M19736 strains disseminated simultaneously the acquired conjugative plasmids in different combinations though selection was ceftazidime in all cases. Finally, we isolated and characterized the extracellular vesicles (EVs) from the native and evolved XDR-E. coli M19736 strains. Interestingly, EVs from the evolved XDR-E. coli M19736 harbored bla CTX-M-15 though the pDCAG1-CTX-M-15 was previously lost as shown by WGS and experiments, suggesting that EV could be a relevant reservoir of ARG for susceptible bacteria. These results evidenced the genetic plasticity of a sporadic clone of E. coli such as ST615 that could play a relevant transitional link in the clinical dynamics and evolution to multidrug/extensively/pandrug-resistant phenotypes of superbugs within the nosocomial niche by acting simultaneously as a vector and reservoir of multiple ARGs which later could be disseminated.

Impact of COVID-19 on diabetes care: mixed methods study in an Indigenous area of Guatemala.

INTRODUCTION: SARS-CoV-2 has impacted globally the care of chronic diseases. However, direct evidence from certain vulnerable communities, such as Indigenous communities in Latin America, is missing. We use observational data from a health district that primarily serves people of Maya K'iche' ethnicity to examine the care of type 2 diabetes in Guatemala during the pandemic. METHODS: We used a parallel convergent mixed methods design. Quantitative data (n=142 individuals with diabetes) included glycated haemoglobin (HbA1c), blood pressure, body mass index and questionnaires on diabetes knowledge, self-care and diabetes distress. Quantitative data was collected at two points, at baseline and after COVID restrictions were lifted. For quantitative outcomes, we constructed multilevel mixed effects models with multiple imputation for missing data. Qualitative data included interviews with providers, supervisors and individuals living with diabetes (n=20). We conducted thematic framework analysis using an inductive approach. RESULTS: Quantitative data was collected between June 2019 and February 2021, with a median of 487 days between data collection points. HbA1c worsened +0.54% (95% CI, 0.14 to 0.94) and knowledge about diabetes decreased -3.54 points (95% CI, -4.56 to -2.51). Qualitatively, the most important impact of the pandemic was interruption of the regular timing of home visits and peer group meetings which were the standard of care. CONCLUSIONS: The deterioration of diabetes care was primarily attributed to the loss of regular contact with healthcare workers. The results emphasize the vulnerability of rural and Indigenous populations in Latin America to the suspension of chronic disease care.