Corrosion Risk to Metal-Based Artefacts in a Scientific and Technical Museum: An Assessment of Environmental and Exhibition Conditions.

Materials such as wood, textiles, or plastics that are part of the exhibition system in museums are known to emit pollutants such as organic acids. Scientific and technical objects that include these materials in their composition can themselves be a potential source of emissions, which, together with inappropriate humidity and temperature conditions, can lead to corrosion of the metallic parts. In this work, we have studied the corrosivity of different locations in two venues of the Spanish National Museum of Science and Technology (MUNCYT). Coupons of the most representative metals from the collection were placed in different showcases and rooms for 9 months. The corrosion of the coupons has been evaluated in terms of the rate of mass gain, colour changes and characterisation of the corrosion products. The results were correlated to the relative humidity and concentration of gaseous pollutants to determine which metals are most susceptible to corrosion. The results show that metal artefacts exposed in showcases have a higher risk of corrosion than those exposed directly in the room, and that some pollutants are emitted by the artefacts. The corrosivity of the museum environment is low for copper, brass, and aluminium in most locations; however, some placements present a higher aggressivity for steel and lead, due to the high humidity and the presence of organic acids.

Leukocyte Nuclear Morphology Alterations in Dilated Cardiomyopathy Caused by a Lamin AC Truncating Mutation (LMNA/Ser431*) Are Modified by the Presence of a LAP2 Missense Polymorphism (TMPO/Arg690Cys).

The clinical phenotype of LMNA-associated dilated cardiomyopathy (DCM) varies even among individuals who share the same mutation. LMNA encodes lamin AC, which interacts with the lamin-associated protein 2 alpha (LAP2α) encoded by the TMPO gene. The LAP2α/Arg690Cys polymorphism is frequent in Latin America and was previously found to disrupt LAP2α-Lamin AC interactions in vitro. We identified a DCM patient heterozygous for both a lamin AC truncating mutation (Ser431*) and the LAP2α/Arg690Cys polymorphism. We performed protein modeling and docking experiments, and used confocal microscopy to compare leukocyte nuclear morphology among family members with different genotype combinations (wild type, LAP2α Arg690Cys heterozygous, lamin AC/Ser431* heterozygous, and LAP2α Arg690Cys/lamin AC Ser431* double heterozygous). Protein modeling predicted that 690Cys destabilizes the LAP2α homodimer and impairs lamin AC-LAP2α docking. Lamin AC-deficient nuclei (Ser431* heterozygous) showed characteristic blebs and invaginations, significantly decreased nuclear area, and increased elongation, while LAP2α/Arg690Cys heterozygous nuclei showed a lower perimeter and higher circularity than wild-type nuclei. LAP2α Arg690Cys apparently attenuated the effect of LMNA Ser431* on the nuclear area and fully compensated for its effect on nuclear circularity. Altogether, the data suggest that LAP2α/Arg690Cys may be one of the many factors contributing to phenotype variation of LMNA-associated DCM.

Midazolam/fentanyl vs. propofol/remifentanil in immediate postoperative with short-term mechanical ventilation.

OBJECTIVES: To compare between 2 sedoanalgesia regimes, the time from withdrawal of the medication until the patient wakes up and until extubation. METHODOLOGY: Observational study on pediatric patients after elective surgery that needed mechanical ventilation for a period maximum to 72 h. We compared two independent groups of patients: group A: patients collected prospectively who received sedoanalgesia with propofof-remifentanil and group B: patients who received midazolam-fentanyl collected retrospectively by reviewing medical records and database of the unit. The main variables studied were: Age, weight, sex, interventions type, sedoanalgesia scales, drugs dosages, time from withdrawal of medication to awakening and extubation, and adverse effects. RESULTS: We collected 82 patients, 43 in group A and 39 in group B. Age (arithmetical mean ±â€¯standard deviation of patients were 49 ±â€¯65 months, weight 17 ±â€¯16 kg. Mechanical ventilation medium time was 22 h (3-72), wake-up time from withdrawal after removing sedoanalgesia was of 11,8 ±â€¯10,6 min group A and 137,3 ±â€¯45 min group B (P < 0.001), extubation time after removing sedoanalgesia was of 24 ±â€¯21 min group A and 230 ±â€¯102 min group B (P < 0.001). Adverse effects were found in 10.5% of patients group A (7.9% agitation, 2.6% bradycardia), and 13% of patients group B (respiratrory depression after extubation) P = 0,572. CONCLUSIONS: Patients treated with propofol-remifentanil have significantly shorter times to wake up, extubation and withdrawal from mechanical ventilation after stopping the medication. In the midazolam-fentanyl group, respiratory depression was more frequent, although the percentage of adverse effects were similar in both groups. Both the combination of propofol-remifentanil and midazolam-fentanyl appear to be effective as a sedative-analgesic regimen for patients undergoing mechanical ventilation after surgery.

Fanconi Anemia Patients from an Indigenous Community in Mexico Carry a New Founder Pathogenic Variant in FANCG.

Fanconi anemia (FA) is a rare genetic disorder caused by pathogenic variants (PV) in at least 22 genes, which cooperate in the Fanconi anemia/Breast Cancer (FA/BRCA) pathway to maintain genome stability. PV in FANCA, FANCC, and FANCG account for most cases (~90%). This study evaluated the chromosomal, molecular, and physical phenotypic findings of a novel founder FANCG PV, identified in three patients with FA from the Mixe community of Oaxaca, Mexico. All patients presented chromosomal instability and a homozygous PV, FANCG: c.511-3_511-2delCA, identified by next-generation sequencing analysis. Bioinformatic predictions suggest that this deletion disrupts a splice acceptor site promoting the exon 5 skipping. Analysis of Cytoscan 750 K arrays for haplotyping and global ancestry supported the Mexican origin and founder effect of the variant, reaffirming the high frequency of founder PV in FANCG. The degree of bone marrow failure and physical findings (described through the acronyms VACTERL-H and PHENOS) were used to depict the phenotype of the patients. Despite having a similar frequency of chromosomal aberrations and genetic constitution, the phenotype showed a wide spectrum of severity. The identification of a founder PV could help for a systematic and accurate genetic screening of patients with FA suspicion in this population.

Pediatric Emergency Department Management of C1 Inhibitor Deficiency.

INTRODUCTION: C1 inhibitor deficiency is a rare, potentially life-threatening syndrome. Acute attacks of angioedema may occur at any time, so the emergency department (ED) constitutes an indispensable component of its care. AIM: To describe the reasons for consultation by children with C1 inhibitor deficiency at the ED, as well as its management and complications. PATIENTS AND METHODS: This is a longitudinal retrospective study conducted in a pediatric ED of a tertiary care hospital in Madrid. The study includes children with C1 inhibitor deficiency, aged 0 to 16 years, who had consulted the ED for whatever reason, over a span of 9 years (2011-2020). Analyzed data include the following: age, sex, type of disease, reason for query, complementary examinations, established diagnosis, treatment, number of visits to the ED, length of ED stay, and admissions. RESULTS: Sixteen patients, amounting a total of 83 ED visits, were analyzed. Fifty-six percent were boys, and the median age was 6.9 years (5 months to 15.9 years). The median and mean of number of visits to the ED per patient was 2 (1-22) and 5.2 ± 6.11, respectively. There were 85.5% of the ED visits initially attributed to acute angioedema attacks. Additional tests were conducted in 30.1%, and 31.3% required C1 inhibitor concentrate. Three episodes required hospital admission (3.6%), and there were no complications. The stay in the ED was longer for patients who needed specific intravenous treatment. CONCLUSIONS: C1 inhibitor deficiency is a rare disease that may require ED care. The main reasons for ED visits were respiratory problems, and the main location of the acute attacks of angioedema were abdominal and cutaneous. Almost one third of the ED visits needed specific treatment, resulting in longer stays. A proper management in the ED and the specific treatment with C1 inhibitor concentrate were effective in 96.2% of the acute attacks of angioedema. Knowledge of this disease in the ED is key to prevent complications.

Guía clínica chilena para el estudio y tratamiento de hidradenitis supurativa. Resumen ejecutivo

Hidradenitis suppurativa is a chronic inflammatory disease of the hair follicle characterized by recurrent painful and inflamed lesions, predominantly affecting intertriginous regions. Due to its physical sequelae and impact on quality of life, we should be familiarized with this disease to make an appropriate diagnosis and implement an early treatment. This executive summary of the clinical guideline, elaborated by the hidradenitis suppurativa workgroup of the Chilean Society of Dermatology and Venereology (SOCHIDERM), reviews its definition, epidemiology, pathophysiology, risk factors, comorbidities, psycho-emotional impact, clinical presentation, diagnosis, classifications, ultrasonographic evaluation, and its medical and surgical treatments. Finally, a therapeutic approach algorithm is proposed.

The Effect of Arabinoxylan and Wheat Bran Incorporation on Dough Rheology and Thermal Processing of Rotary-Moulded Biscuits.

Wheat bran incorporation into biscuits may increase their nutritional value, however, it may affect dough rheology and baking performance, due to the effect of bran particles on dough structure and an increase in water absorption. This study analyzed the enrichment effect of wheat bran and arabinoxylans, the most important non-starch polysaccharides found in whole wheat flour, on dough rheology and thermal behaviour during processing of rotary-moulded biscuits. The objective was to understand the contribution of arabinoxylans during biscuit-making and their impact when incorporated as wheat bran. Refined flour was replaced at 25, 50, 75, or 100% by whole flour with different bran particle sizes (fine: 4% > 500 µm; coarse: 72% > 500 µm). The isolated effect of arabinoxylans was examined by preparing model flours, where refined flour was enriched with water-extractable and water-unextractable arabinoxylans. Wheat bran had the greatest impact on dough firmness and arabinoxylans had the greatest impact on the elastic response. The degree of starch gelatinization increased from 24 to 36% in biscuits enriched with arabinoxylans or whole flour and coarse bran. The microstructural analysis (SEM, micro-CT) suggested that fibre micropores may retain water inside their capillaries which can be released in a controlled manner during baking.

Interaction of HLA Class II rs9272219 and TMPO rs17028450 (Arg690Cys) Variants Affects Neuromyelitis Optica Spectrum Disorder Susceptibility in an Admixed Mexican Population.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a demyelinating autoimmune disease of the central nervous system, more prevalent in individuals of non-European ancestry. Few studies have analyzed genetic risk factors in NMOSD, and HLA class II gene variation has been associated NMOSD risk in various populations including Mexicans. Thymopoietin (TMPO) has not been tested as a candidate gene for NMOSD or other autoimmune disease, however, experimental evidence suggests this gene may be involved in negative selection of autoreactive T cells and autoimmunity. We thus investigated whether the missense TMPO variant rs17028450 (Arg630Cys, frequent in Latin America) is associated with NMOSD, and whether this variant shows an interaction with HLA-class II rs9272219, previously associated with NMOSD risk. A total of 119 Mexican NMOSD patients, 1208 controls and 357 Native Mexican individuals were included. The HLA rs9272219 "T" risk allele frequency ranged from 21 to 68%, while the rs17028450 "T" minor allele frequency was as high as 18% in Native Mexican groups. Both rs9272219 and rs17028450 were significantly associated with NMOSD risk under additive models (OR = 2.48; p = 8 × 10-10 and OR = 1.59; p = 0.0075, respectively), and a significant interaction between both variants was identified with logistic regression models (p = 0.048). Individuals bearing both risk alleles had an estimated 3.9-fold increased risk of NMOSD. To our knowledge, this is the first study reporting an association of TMPO gene variation with an autoimmune disorder and the interaction of specific susceptibility gene variants, that may contribute to the genetic architecture of NMOSD in admixed Latin American populations.

[Midazolam/fentanyl vs propofol/remifentanil in immediate postoperative with short-term mechanical ventilation]. / Sedoanalgesia con midazolam/fentanilo vs. propofol/remifentanilo en postoperatorio inmediato con ventilación mecánica de corta duración.

OBJECTIVES: Compare between 2sedoanalgesia regimes, the time from withdrawal of the medication until the patient wakes up and until extubation. METHODOLOGY: Observational study on pediatric patients after elective surgery that needed mechanical ventilation for a period maximum to 72hours. We compared 2independent groups of patients: group A: patients collected prospectively who received sedoanalgesia with propofof-remifentanil and group B: patients who received midazolam-fentanyl collected retrospectively by reviewing medical records and database of the unit. The main variables studied were: Age, weight, sex, interventions type, sedoanalgesia scales, drugs dosages, time from withdrawal of medication to awakening and extubation, and adverse effects. RESULTS: We collected 82 patients, 43 in group A and 39 in group B. Age (arithmetical mean±standard deviation of patients were 49±65 months, weight 17±16kg. Mechanical ventilation time medium was 22hours (3-72), wake-up time from withdrawal after removing sedoanalgesia was of 11,8±10,6minutes group A and 137,3±45minutes group B (P<.001), extubation time after removing sedoanalgesia was of 24±21minutes group A and 230±102minutes group B (P<.001). Adverse effects were found in 10.5% of patients group A (7.9% agitation, 2.6% bradycardia), and 13% of patients group B (respiratrory depression after extubation), P=.572. CONCLUSIONS: Patients treated with propofol-remifentanil have significantly shorter times to wake up, extubation and withdrawal from mechanical ventilation after stopping the medication. In the midazolam-fentanyl group, respiratory depression was more frequent, although the percentage of adverse effects were similar in both groups. Both the combination of propofol-remifentanil and midazolam-fentanyl appear to be effective as a sedative-analgesic regimen for patients undergoing mechanical ventilation after surgery.

[Chilean clinical guideline for the management of hidradenitis suppurativa - executive summary]. / Guía clínica chilena para el estudio y tratamiento de hidradenitis supurativa. Resumen ejecutivo.

Hidradenitis suppurativa is a chronic inflammatory disease of the hair follicle characterized by recurrent painful and inflamed lesions, predominantly affecting intertriginous regions. Due to its physical sequelae and impact on quality of life, we should be familiarized with this disease to make an appropriate diagnosis and implement an early treatment. This executive summary of the clinical guideline, elaborated by the hidradenitis suppurativa workgroup of the Chilean Society of Dermatology and Venereology (SOCHIDERM), reviews its definition, epidemiology, pathophysiology, risk factors, comorbidities, psycho-emotional impact, clinical presentation, diagnosis, classifications, ultrasonographic evaluation, and its medical and surgical treatments. Finally, a therapeutic approach algorithm is proposed.

Genomic study of dilated cardiomyopathy in a group of Mexican patients using site-directed next generation sequencing.

BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of nonischemic heart failure and death in young adults. Next generation sequencing (NGS) has become part of the diagnostic workup in idiopathic and familial DCM. More than 50 DCM genes have been identified, revealing great molecular heterogeneity and variable diagnostic yield. Interpretation of variant pathogenicity is challenging particularly in underrepresented populations, as pathogenic variant databases include studies mainly from European/Caucasian populations. To date, no studies on genomic diagnosis of DCM have been conducted in Mexico. METHODS: We recruited 55 unrelated DCM patients, 22 familial (F-DCM), and 33 idiopathic (I-DCM), and performed site-directed NGS seeking causal mutations. Diagnostic yield was defined as the proportion of individuals with at least one pathogenic (P) or likely pathogenic (LP) variant in DCM genes. RESULTS: Overall diagnostic yield was 47.3%, and higher in F-DCM (63.6%) than in I-DCM (36.4%, p = 0.047). Overall, NGS disclosed 41 variants of clinical interest (61.0% novel), 27 were classified as P/LP and 14 of unknown clinical significance. Of P/LP variants, 10 were A-band region TTN truncating variants, five were found in DSP (18.5%), five in MYH7 (18.5%), two in LMNA (7.4%), and one in RBM20, ABCC9, FKTN, ACTA1, and TNNT2. NGS findings suggested autosomal recessive inheritance in three families, two with DSP loss of function mutations in affected individuals. The increasing number of mutation reports in DCM, increasing knowledge on the functional consequences of mutations, mutational hotspots and functional domains of DCM-related proteins, the recent refinement ACMG/ClinGen Guidelines, and co-segregation analysis in DCM families helped increase the diagnostic yield. CONCLUSION: This is the first NGS study performed in a group of Mexican DCM patients, contributing to understand the mutational spectrum and complexity of DCM molecular diagnosis.

Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population.

Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10-6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10-10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.

Sex-specific gene expression differences in reproducing Syllis prolifera and Nudisyllis pulligera (Annelida, Syllidae).

Syllidae is an annelid family characterized by its complex life cycles involving some of the most outstanding annelid reproductive strategies. Syllid reproductive modes sometimes imply the modification of the posterior body to form independent reproductive units (schizogamy) or the development of swimming adults (epigamy). These modes of sexual reproduction have been studied for more than 150 years, and yet, little is known regarding their molecular background. Notably, while several studies during the last three decades have revealed details about molecular mechanisms involved in the reproduction of some few model annelids, studies focusing on syllids remain limited. Thus, we performed differential gene expression analyses of female, male, and non-reproducing individuals of Syllis prolifera (schizogamic) and Nudisyllis pulligera (epigamic), as representatives of two different reproductive strategies. For that, transcriptomes from specimens of three conditions (non-reproducing, male, female) were de novo assembled and annotated for S. prolifera and N. pulligera. We found rather similar gene expression profiles for female and non-reproducing individuals, while male gene expression is clearly different. Although previous studies have suggested that femininity in syllids might require additional signalling, our analyses support a scenario, where masculinity may also involve several specific genetic processes.

Guía clínica chilena para el manejo de hidradenitis supurativa / Chilean clinical guidelines for the management of hidradenitis suppurativa

La hidradenitis supurativa es una enfermedad inflamatoria crónica del folículo piloso que se caracteriza por la aparición recurrente de lesiones inflamatorias dolorosas y profundas predominantemente en pliegues. Debido a sus secuelas físicas y en la calidad de vida, debemos estar familiarizados con esta enfermedad, a fin de poder realizar un diagnóstico oportuno e implementar un tratamiento precoz. Esta guía clínica, elaborada por el grupo de trabajo de hidradenitis supurativa de la Sociedad Chilena de Dermatología y Venereología (SOCHIDERM), revisa su definición, epidemiología, fisiopatogenia, factores de riesgo, comorbilidades, impacto psicoemocional, presentación clínica, diagnóstico, clasificaciones, evaluación ecográfica, y tratamientos médico y quirúrgico. Finalmente se propone un algoritmo de enfrentamiento terapéutico.

Hidradenitis suppurativa is a chronic inflammatory disease of the hair follicle characterized by recurrent painful and inflamed lesions, predominantly affecting intertriginous regions. Due to its physical sequelae and impact on life quality, we should be familiarized with this disease to make an appropriate diagnosis and implement an early treatment. This clinical guideline, elaborated by the hidradenitis suppurativa workgroup of the Chilean Society of Dermatology and Venereology (SOCHIDERM), review its definition, epidemiology, pathophysiology, risk factors, comorbidities, psycho-emotional impact, clinical presentation, diagnosis, classifications, ultrasonographic evaluation, and its medical and surgical treatments. Finally, a therapeutic approach algorithm is proposed.

Boxeo amateur español: origen y evolución hasta los juegos olímpicos de Tokio-1964 / Boxe amador espanhol: origem e evolução até os jogos olímpicos de Tokyo-1964 / Spanish amateur boxing: origin and evolution until the 1964 Tokyo olympic games

Esta investigación recupera los hechos y circunstancias históricas que envolvieron el boxeo desde su origen en las estructuras federativas españolas hasta la participación española en los Juegos Olímpicos de Tokio en 1964. Este trabajo historiográfico utilizó el análisis documental y la entrevista semiestructurada para recuperar y contrastar información de archivos institucionales, personales y hemerográficos, rescatando contenidos inéditos del archivo personal y de la entrevista a un boxeador participante en Tokio-64. Madrid y Barcelona impulsaron la práctica pugilística en España en las primeras décadas del siglo XIX. La llegada de púgiles extranjeros propició la estructuración y regulación del boxeo y, como resultado, en 1922 se fundó la Federación Española de Boxeo, que formó parte de las estructuras olímpicas. La Guerra Civil española supuso un receso, pero en los años 60 surgió una generación de boxeadores que, a pesar de precarias circunstancias, lograron asistir a los Juegos Olímpicos y pródigas victorias posteriores.

Esta investigação recupera os factos e circunstâncias históricas que envolveram o boxe desde a sua origem nas estruturas federativas espanholas até a participação espanhola nos Jogos Olímpicos de Tóquio, em 1964. Este trabalho historiográfico utilizou análise documental e entrevistas semiestruturadas para recuperar e contrastar informações dos arquivos institucionais, pessoais e jornalísticos, recolhendo informação inédita do arquivo pessoal e da entrevista de um boxeador participante em Tóquio-64. Madrid e Barcelona promoveram a prática pugilística na Espanha nas primeiras décadas do século XIX. A chegada dos boxeadores estrangeiros levou à estruturação e à regulamentação do boxe e, em consequência, em 1922, foi fundada a Federação Espanhola de Boxe, que passou a fazer parte das estruturas olímpicas. A Guerra Civil espanhola significou uma pausa, mas nos anos 1960 surgiu uma geração de boxeadores que, apesar das circunstâncias precárias, conseguiram comparecer aos Jogos Olímpicos e ter muitas vitórias subsequentes.

This research revisits the historical facts and circumstances that involved boxing from its origin in the Spanish federative structures to Spain's participation in the 1964 Tokyo Olympic Games. This historiographic study used documentary analysis and semi-structured interviews to revisit and contrast information from institutional, personal and newspaper archives, gathering unpublished content from the personal archive and from the interview with a boxer who participated in Tokyo '64. Madrid and Barcelona promoted pugilistic practice in Spain in the first decades of the nineteenth century. The arrival of foreign fighters favored the structuring and regulation of boxing and, as a result, in 1922 the Spanish Boxing Federation was founded and became part of the Olympic structures. The Spanish Civil War was a setback, but in the 1960s a generation of boxers emerged who, despite precarious circumstances, managed to attend the Olympic Games and win many subsequent victories.

Influence of Genetic and Non-Genetic Risk Factors for Serum Uric Acid Levels and Hyperuricemia in Mexicans.

Risk of hyperuricemia is modified by genetic and environmental factors. Our aim was to identify factors associated with serum uric acid levels and hyperuricemia in Mexicans. A pilot Genome-wide association study GWAS was performed in a subgroup of participants (n = 411) from the Health Workers Cohort Study (HWCS). Single nucleotide polymorphisms (SNPs) associated with serum uric acid levels were validated in all the HWCS participants (n = 1939) and replicated in independent children (n = 1080) and adult (n = 1073) case-control studies. The meta-analysis of the whole HWCS and replication samples identified three SLC2A9 SNPs: rs1014290 (p = 2.3 × 10-64), rs3775948 (p = 8.2 × 10-64) and rs11722228 (p = 1.1 × 10-17); and an ABCG2 missense SNP, rs2231142 (p = 1.0 × 10-18). Among the non-genetic factors identified, the visceral adiposity index, smoking, the metabolic syndrome and its components (waist circumference, blood pressure, glucose and hyperlipidemia) were associated with increased serum uric acid levels and hyperuricemia (p < 0.05). Among the female HWCS participants, the odds ratio for hyperuricemia was 1.24 (95% CI, 1.01-1.53) per unit increase in soft drink consumption. As reported in other studies, our findings indicate that diet, adiposity and genetic variation contribute to the elevated prevalence of hyperuricemia in Mexico.

Host Genetics, Diet, and Microbiome: The Role of AMY1.

Host gene variants selected by diet adaptation have been associated with the microbiome. Poole et al. (Cell Host Microbe 2019;25;553-564.E7) reported that AMY1 copy number, associated with obesity, also impacts microbiome composition and function. Complex genetics-diet-microbiome interactions and their effect on obesity could eventually translate into personalized nutrition.

Exercise Induces White Adipose Tissue Browning Across the Weight Spectrum in Humans.

While the effect of exercise on white adipose tissue browning and metabolic improvement in rodents is clear, there are few studies in humans with inconclusive results. Thus, the aim of the study was to assess whether an exercise intervention promotes subcutaneous adipose tissue browning in humans, and whether this response is associated with metabolic improvement in three groups of individuals defined by body mass index (BMI) (kg/m2). Sedentary adult subjects with different BMI were enrolled in a 12-week bicycle-training program (3 times per week, intensity 70-80% HRmax). Brown and beige gene expression in subcutaneous adipose tissue (scWAT) biopsies, and serum glucose, insulin, lipid, adipokine, and myokine levels were compared before and after the exercise intervention. Thirty-three non-diabetic subjects (mean age 30.4 ± 4.6 years; 57.57% female; 13 normal weight, 10 overweight and 10 with obesity) completed the exercise intervention. Without any significant change in body composition, exercise improved several metabolic parameters, most notably insulin resistance and particularly in the overweight group. Circulating adiponectin, apelin, and irisin exercise-induced changes predicted 60% of the insulin sensitivity improvement. After exercise UCP1, TBX1, CPT1B scWAT expression significantly increased, along with P2RX5 significant positive staining. These changes are compatible with scWAT browning, however, they were not associated with glucose metabolism improvement. In conclusion, 12-weeks of exercise training produced brown/beige gene expression changes in abdominal scWAT of non-diabetic individuals with different BMI, which did not contribute to the metabolic improvement. However, this result should not be interpreted as a lack of effect of browning on metabolic parameters. These findings suggest that a bigger effect is needed and should not preclude the development of more effective strategies of browning. Furthermore, exercise-induced changes in adiponectin, apelin, and irisin predicted insulin sensitivity improvement, supporting the important role of adipokines and myokines in metabolism homeostasis.

Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR) and display trypanocidal activity.

Crassiflorone is a natural product with anti-mycobacterial and anti-gonorrhoeal properties, isolated from the stem bark of the African ebony tree Diospyros crassiflora. We noticed that its pentacyclic core possesses structural resemblance to the quinone-coumarin hybrid 3, which we reported to exhibit a dual-targeted inhibitory profile towards Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR). Following this basic idea, we synthesized a small library of crassiflorone derivatives 15-23 and investigated their potential as anti-trypanosomatid agents. 19 is the only compound of the series showing a balanced dual profile at 10 µM (% inhibitionTbGAPDH = 64% and % inhibitionTcTR = 65%). In phenotypic assay, the most active compounds were 18 and 21, which at 5 µM inhibited Tb bloodstream-form growth by 29% and 38%, respectively. Notably, all the newly synthesized compounds at 10 µM did not affect viability and the status of mitochondria in human A549 and 786-O cell lines, respectively. However, further optimization that addresses metabolic liabilities including solubility, as well as cytochromes P450 (CYP1A2, CYP2C9, CYP2C19, and CYP2D6) inhibition, is required before this class of natural product-derived compounds can be further progressed.