International scope of biomedical research ethics review.

Many countries consider long-term implications for society.

Intranasal Versus Intravenous Dexamethasone to Treat Hospitalized COVID-19 Patients: A Randomized Multicenter Clinical Trial.

BACKGROUND: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability. AIMS: To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19. METHODS: A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded. RESULTS: Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died. CONCLUSIONS: IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration.

Metabolomic Phenotype of Hepatic Steatosis and Fibrosis in Mexican Children Living with Obesity.

Background and Objectives: Metabolic-dysfunction-associated steatotic liver disease or MASLD is the main cause of chronic liver diseases in children, and it is estimated to affect 35% of children living with obesity. This study aimed to identify metabolic phenotypes associated with two advanced stages of MASLD (hepatic steatosis and hepatic steatosis plus fibrosis) in Mexican children with obesity. Materials and Methods: This is a cross-sectional analysis derived from a randomized clinical trial conducted in children and adolescents with obesity aged 8 to 16 years. Anthropometric and biochemical data were measured, and targeted metabolomic analyses were carried out using mass spectrometry. Liver steatosis and fibrosis were estimated using transient elastography (Fibroscan® Echosens, Paris, France). Three groups were studied: a non-MASLD group, an MASLD group, and a group for MASLD + fibrosis. A partial least squares discriminant analysis (PLS-DA) was performed to identify the discrimination between the study groups and to visualize the differences between their heatmaps; also, Variable Importance Projection (VIP) plots were graphed. A VIP score of >1.5 was considered to establish the importance of metabolites and biochemical parameters that characterized each group. Logistic regression models were constructed considering VIP scores of >1.5, and the receiver operating characteristic (ROC) curves were estimated to evaluate different combinations of variables. Results: The metabolic MASLD phenotype was associated with increased concentrations of ALT and decreased arginine, glycine, and acylcarnitine (AC) AC5:1, while MASLD + fibrosis, an advanced stage of MASLD, was associated with a phenotype characterized by increased concentrations of ALT, proline, and alanine and a decreased Matsuda Index. Conclusions: The metabolic MASLD phenotype changes as this metabolic dysfunction progresses. Understanding metabolic disturbances in MASLD would allow for early identification and the development of intervention strategies focused on limiting the progression of liver damage in children and adolescents.

SRT2183 and SRT1720, but not Resveratrol, Inhibit Osteoclast Formation and Resorption in the Presence or Absence of Sirt1.

Background: Osteoclastic bone resorption markedly increases with aging, leading to osteoporosis characterized by weak and fragile bones. Mice exhibit greater bone resorption and poor bone mass when Sirt1 is removed from their osteoclasts. Here we investigated the ex vivo impacts of putative Sirt1 activators, Resveratrol (RSV), SRT2183, and SRT1720, on osteoclast formation and activity in primary mouse bone marrow cells (BMCs) derived from wild-type (WT) and osteoclast specific Sirt1 knockout (OC-Sirt1KO) mice and in the RAW264.7 mouse macrophage cell line. Results: We found that SRT2183 and SRT1720 inhibit the formation of osteoclasts and actin belts in BMCs and RAW264.7 cells, whereas RSV does not. We also observed that the OC-Sirt1KO mice exhibited less bone mineral density, and the BMCs harvested from these mice yielded more osteoclasts than BMCs harvested from littermate controls. Interestingly, both SRT2183 and SRT1720 reduced osteoclast and actin belt formation in BMCs from OC-Sirt1KO mice. SRT2183 and SRT1720 also significantly disrupted actin belts of mature osteoclasts generated from BMCs of WT mice, within 3 and 6 hours of administration, respectively. Furthermore, these compounds inhibited the resorption activity of mature osteoclasts, while RSV did not. Conclusion: Our findings suggest SRT2183 and SRT1720 impede bone resorption by disrupting actin belts of mature osteoclasts, inhibit actin belt formation, and inhibit osteoclastogenesis even in the absence of Sirt1. Thus, the mechanism of action of these compounds appears to extend beyond Sirt1 activation and possibly pave the way for potential new therapies in alleviating osteoporosis associated bone loss.

Side switch frequency while masticating different chewing materials, and its relationship with other masticatory behaviors and sensory perceptions.

OBJECTIVE: This cross-sectional study aimed to establish normative values for masticatory side switch (MSS) frequency in young Mexican adults and to assess the relationship between various indices and MSS frequency when masticating different chewing materials. DESIGN: We enrolled 101 dentate adults and performed four masticatory assays that involved masticating different chewing materials (i.e., two-colored chewing gum, sweet cracker, salty cracker, and bread). Participants were asked to eat and swallow these foods and to chew the gum for 40 cycles and the following indices were determined: MSS index (MSSI), unilateral chewing index, chewing cycle duration, and number of cycles before terminal swallowing. The participants then rated perceived flavor intensity, salivary flow, and muscle fatigue during each trial. RESULTS: The MSSI ranged from 0.03-0.06 (10th percentile) to 0.48-0.54 (90th percentile). A repeated-measures general linear model revealed a mean MSSI value of 0.28 (95 %CI, 0.25-0.30) adjusted by several factors. Male sex, soft food, and the last chewing period were associated with lower MSS frequency. Spearman's test showed a high correlation for the MSSI among the different foods. MSSI correlated negatively with the unilateral chewing index for each chewing material and with number of cycles for the sweet cracker. However, no significant correlation was detected between MSSI and sensory perception. CONCLUSIONS: In healthy dentate individuals, the mean MSS relative frequency is 25-30 % with an 80-central percentile of 5-50 % of the maximum possible side changes. Lower MSS frequencies were detected in men, when chewing soft food, and during the final chewing period.

Valoración y seguimiento de pacientes con talla baja en Atención Primaria / Evaluation and follow up of patients with short stature in Primary Care

Introducción: entre las funciones del pediatra de Atención Primaria está la valoración antropométrica. Es importante incluirla en las revisiones del niño sano para detectar casos de talla baja, estudiarlos, derivarlos a Endocrinología si es preciso y realizar el tratamiento correspondiente. Objetivo: describir y analizar el manejo de niños con talla baja en un centro de salud de Atención Primaria. Material y métodos: estudio descriptivo retrospectivo sobre niños con talla baja de entre 2 y 16 años, cuyo centro de salud es el de Villaviciosa de Odón, del 1 de enero de 2020 al 1 de enero de 2022. Se seleccionaron las historias clínicas con la aplicación Consult@web y se revisaron en AP Madrid y Horus. Se realizó el análisis estadístico mediante SPSS. Resultados: se seleccionaron 62 pacientes, de los cuales 19 cumplían criterios de talla baja. Un 16% tenía antecedentes de talla baja familiar y un 16%, de retraso constitucional de crecimiento y desarrollo. La talla media al diagnóstico fue -2,36 ± 0,49 desviaciones estándar. Las pruebas complementarias más frecuentemente solicitadas fueron edad ósea (74%) y analítica de sangre (78%). El diagnóstico más frecuente fue talla baja idiopática (58%). Un 32% recibió tratamiento con hormona de crecimiento. El seguimiento se realizó exclusivamente en Atención Primaria en el 32%. Ante el pequeño tamaño muestral, no se ha obtenido significación estadística en las comparaciones. Conclusiones: la talla baja es un motivo frecuente de consulta en Atención Primaria, siendo importante realizar una valoración completa, reconociendo aquellos datos de alarma que hagan sospechar patología asociada (AU)

Introduction: anthropometric assessment is one of the functions of the Primary Care pediatrician. It is important to include it in healthy children check-ups in order to detect those cases of short stature, study them, refer them to Endocrinology if necessary and carry out the corresponding treatment.Objective: to describe and analyze the management of children with short stature in a primary care health center.Material and methods: retrospective descriptive study on children with short stature between 2 and 16 years of age, whose Health Center is Villaviciosa de Odón, from January 1, 2020 to January 1, 2022. The medical records were selected in the Consult@web application and reviewed in AP Madrid and Horus. Statistical analysis was performed using SPSS.Results: 62 patients were studied, of whom 19 met the criteria for short stature. 16% had a family history of short stature and 16% had a history of constitutional delay of growth. Mean height at diagnosis was -2,36 ± 0,49 SD. The most frequently requested complementary tests were bone age (74%) and blood tests (78%). The most frequent diagnosis was idiopathic short stature (58%). 32% received growth hormone treatment. Follow-up was carried out exclusively in primary care in 32%. Given the small sample size, no statistical significance was obtained in the comparisons.Conclusions: short stature is a frequent reason for consultation in Primary Care, being important to perform a complete evaluation recognizing those alarming data that lead to suspect associated pathology. (AU)

Revised molecular phylogeny, global biogeography, and diversification of palms subfamily Coryphoideae (Arecaceae) based on low copy nuclear and plastid regions.

Coryphoideae are palmate-leaved palms from the family Arecaceae consisting of 46 genera representing 421 species. Although several phylogenetic analyses based on different genomic regions have been carried out on Coryphoideae, a fully resolved molecular phylogenetic tree has not been reported yet. To achieve this, we applied two phylogenetic reconstruction methods: Maximum Likelihood and Bayesian Inference, using amplified sampling by retrieving chloroplast and nuclear DNA sequences from NCBI and adding newly produced sequences from Indian accession into the dataset. The same dataset (chloroplast + nuclear DNA sequences) was used to estimate divergence times and the evolutionary history of Coryphoideae with a Bayesian uncorrelated, lognormal relaxed-clock approach and a Statistical Divergence-Vicariance Analysis method, respectively. The phylogenetic analyses based on a combined chloroplast and nuclear DNA sequence dataset showed well-resolved relationships within the subfamily. Both phylogenetic trees divide Coryphoideae into two main groups: CSPT (Crysophileae, Sabaleae, Phoeniceae, and Trachycarpeae) and the Syncarpous group. These main groups are segregated into eight tribes (Trachycarpeae, Phoeniceae, Sabaleae, Crysophileae, Borasseae, Corypheae, Caryoteae, and Chuniophoeniceae) and four subtribes (Rhapidine, Livistoninae, Hyphaeninae, and Lataniinae) with strong support-values. Most previously unresolved and doubtful relationships within tribes Trachycarpeae and Crysophilieae are now resolved and well-supported. The reconstructed phylogenetic trees support all previous systematic revisions of the subfamily. All Indian sampled species of Arenga, Bentinckia, Hyphaene, and Trachycarpus show close relation with their respective congeneric species. Molecular dating results and integration of biogeography suggest that Coryphoideae originated in Laurasia at ~95.12 Ma and then diverged into the tropical and subtropical regions of the whole world. This study offers the correct combination of nuclear and plastid regions to test the current and future systematic revisions.

Patterns of Species Richness and Distribution of the Genus Laelia s.l. vs. Laelia s.s. (Laeliinae: Epidendroideae: Orchidaceae) in Mexico: Taxonomic Contribution and Conservation Implications.

Laelia is an endemic genus of the neotropical region, with the greatest richness occurring in Mexico. A recent phylogenetic study transferred some Mexican laelias to the genus Schomburgkia, which has generated debate. The aim of the present study was to analyze the patterns of species richness and endemism and the current and potential geographic distributions of the taxa of Laelia s.l., as well as the putative Laelia s.s., distributed in Mexico as part of an exploratory evaluation of the generic limits to sheds light on the taxonomic debate and generate baselines to guide conservation efforts. A database was generated with information from herbarium specimens and publications. The species richness was estimated by political division, biomes, and elevation. The endemism was analyzed by political division and using the weighted and corrected weighted endemism indices. Geographic data, climatic, and topographic variables were used to predict the distributions with the maximum entropy algorithm. The results supported the proposal to transfer some species to the genus Schomburgkia. Some areas of the Sierra Madre del Sur and Oriental should be included as priority areas in the conservation strategies of Laelia. This study highlights the importance of the taxonomy, distribution, and hotspots in diversity conservation.

¿Cómo realizamos el cribado visual en Atención Primaria? / How is vision screening performed in primary care?

Introducción: la ambliopía es la causa más común de pérdida de visión prevenible en los países desarrollados. Dicha prevención depende de una detección y tratamiento precoces mediante un adecuado cribado visual en la infancia. Nuestro objetivo es describir la situación del cribado visual en Atención Primaria en España y su relación con la formación de los profesionales. Material y métodos: estudio observacional descriptivo mediante encuesta telemática a los pediatras de Atención Primaria acerca de sus conocimientos sobre el desarrollo visual y las técnicas de cribado, material y formación al respecto. Análisis estadístico descriptivo y univariado en busca de relación entre la formación recibida y sus conocimientos. Resultados: el 79,3% de los participantes acierta más de la mitad de las preguntas teóricas. El 82,8% tiene optotipos estandarizados y el 30,7%, el test de Lang. El 72,7% conoce la distancia óptima y el 76,6% la altura óptima para explorar la agudeza visual con optotipos. El 50%, 68,3% y 44,5% realiza el reflejo rojo, el test de Hirschberg y el Cover test en las revisiones indicadas, respectivamente. Más del 90% conoce los criterios de derivación al oftalmólogo. El 3,1% ha recibido formación institucional y el 54,8% autónoma. Existen diferencias en la puntuación obtenida entre los profesionales según la formación recibida. Conclusiones: se detectan aspectos a mejorar. Se debe explorar el reflejo rojo en todas las revisiones del lactante y la alineación ocular desde los 6 meses, así como disponer y mejorar la utilización del test de Lang y de optotipos estandarizados. Existe relación entre un mayor nivel de conocimientos teóricos y prácticos y la formación recibida (AU)

Introduction: amblyopia is the most frequent cause of preventable vision loss in developed countries. Its prevention depends on early detection and treatment through adequate vision screening in childhood. Our objective was to describe the current situation in vision screening at the primary care level in Spain and its association with the training of professionals.Material and methods: observational descriptive study via a remote survey of primary care paediatricians of their knowledge on visual development and vision screening techniques, equipment and training. We conducted a statistical descriptive and univariate analysis to assess the association between the training received and the level of knowledge. Results: of all respondents, 79.3% answered the theoretical questions correction, 82.8% had standardised optotypes and 30.7% used the Lang test. Also, 72.7% knew the adequate distance and 76.6% the optimal height to assess visual acuity with optotypes. Fifty percent used the red reflex test, 68.3% the Hirschberg test and 44.5% the cover test in the appropriate check-ups. As regards training, 3.1% received it from their institutions, and 54.8% independently. Over 90% knew the criteria for referral to the ophthalmologist. We found differences in the scores of the respondents based on the training received.Conclusion: we identified opportunities for improvement: the red reflex test should be performed during all infant check-ups and ocular alignment checked from 6 months, and the Lang test and standardised optotypes should be available and their use improved. Higher levels of theoretical and practical knowledge are positively correlated with the amount of training received by health professionals. (AU)

Phylogenetic Analysis and Flower Color Evolution of the Subfamily Linoideae (Linaceae).

The taxonomy of the subfamily Linoideae at the intergeneric and section levels has been questioned throughout the years, and the evolution of floral characters remains poorly understood. In particular, the evolution of flower color is still uncertain, despite its ecological importance and being one of the most variable and striking traits in Angiospermae. We evaluated the phylogenetic relationships of the genera and sections and used the phylogeny to reconstruct the ancestral state of flower color. The results suggest reevaluating the taxonomic status of segregated genera and re-incorporating them into Linum. Four of the five sections currently accepted were recovered as monophyletic (Cathartolinum, Dasylinum, Linum, and Syllinum). We propose accepting the section Stellerolinon and reevaluating Linopsis, whose representatives were recovered in three separate clades. The ancestral flower color for Linoideae was yellow-white. The flower colors purple and yellow-white were recovered at the deepest nodes of the two main clades. Pink, blue, and red colors were the most recent to evolve. These results appear to be related to diversification events, biogeographical history, and ecological aspects of the subfamily. Our reconstruction constitutes the first plausible scenario that explores the evolution of flower color, leading to new testable hypotheses for future research on the flax group.

Ten-Week Sucralose Consumption Induces Gut Dysbiosis and Altered Glucose and Insulin Levels in Healthy Young Adults.

Sucralose consumption alters microbiome and carbohydrate metabolism in mouse models. However, there are no conclusive studies in humans. Our goals were to examine the effect of sucralose consumption on the intestinal abundance of bacterial species belonging to Actinobacteria, Bacteroidetes, and Firmicutes and explore potential associations between microbiome profiles and glucose and insulin blood levels in healthy young adults. In this open-label clinical trial, volunteers randomly drank water, as a control (n = 20), or 48 mg sucralose (n = 20), every day for ten weeks. At the beginning and the end of the study, participants were subjected to an oral glucose tolerance test (OGTT) to measure serum glucose and insulin every 15 min for 3 h and provided fecal samples to assess gut microbiota using a quantitative polymerase chain reaction. Sucralose intake altered the abundance of Firmicutes without affecting Actinobacteria or Bacteroidetes. Two-way ANOVA revealed that volunteers drinking sucralose for ten weeks showed a 3-fold increase in Blautia coccoides and a 0.66-fold decrease in Lactobacillus acidophilus compared to the controls. Sucralose consumption increased serum insulin and the area under the glucose curve compared to water. Long-term sucralose ingestion induces gut dysbiosis associated with altered insulin and glucose levels during an OGTT.

Intranasal dexamethasone: a new clinical trial for the control of inflammation and neuroinflammation in COVID-19 patients.

BACKGROUND: By end December of 2021, COVID-19 has infected around 276 million individuals and caused over 5 million deaths worldwide. Infection results in dysregulated systemic inflammation, multi-organ dysfunction, and critical illness. Cells of the central nervous system are also affected, triggering an uncontrolled neuroinflammatory response. Low doses of glucocorticoids, administered orally or intravenously, reduce mortality among moderate and severe COVID-19 patients. However, low doses administered by these routes do not reach therapeutic levels in the CNS. In contrast, intranasally administered dexamethasone can result in therapeutic doses in the CNS even at low doses. METHODS: This is an approved open-label, multicenter, randomized controlled trial to compare the effectiveness of intranasal versus intravenous dexamethasone administered in low doses to moderate and severe COVID-19 adult patients. The protocol is conducted in five health institutions in Mexico City. A total of 120 patients will be randomized into two groups (intravenous vs. intranasal) at a 1:1 ratio. Both groups will be treated with the corresponding dexamethasone scheme for 10 days. The primary outcome of the study will be clinical improvement, defined as a statistically significant reduction in the NEWS-2 score of patients with intranasal versus intravenous dexamethasone administration. The secondary outcome will be the reduction in mortality during hospitalization. CONCLUSIONS: This protocol is currently in progress to improve the efficacy of the standard therapeutic dexamethasone regimen for moderate and severe COVID-19 patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04513184 . Registered November 12, 2020. Approved by La Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) with identification number DI/20/407/04/36. People are currently being recruited.

Comparison of Carotid Intima-Media Thickness in Children and Adults With and Without Obesity: A Hysteresis Model.

OBJECTIVE: To describe a third-degree polynomial function (hysteresis) of the effect size of age, obesity, and insulin sensitivity over the carotid intima-media thickness (c-IMT), in the pediatric and adult groups. METHODS: A quasi-experimental study with fixed factor analysis of age (children aged 8-12 years, n = 73; adults aged 21-45 years, n = 82) and obesity (yes, n = 76; no, n = 79) was conducted to analyze the effect on the c-IMT and Matsuda insulin sensitivity index values. This quasi-experimental design was analyzed with robust regression modeling. RESULTS: The additive effect of obesity, independent of age, was evident in the case of the c-IMT values. There was no interaction effect, but a significant difference between participants with normal weight and those with obesity was found (P < .0001). The difference between adults and children was also significant, but the effect size was smaller. A model was created based on age, Tanner stage, and obesity using the c-IMT and Matsuda insulin sensitivity index values. A linear function fit as R2, and the cubic function estimated parameters like a polynomial model. CONCLUSION: This practical study design showed that children with obesity displayed the same levels of carotid intima-media abnormalities as adults with obesity. The polynomial shape of the model suggests potentially poor outcomes that resemble the hysteresis process and may predict chronic cardiometabolic events during early adulthood.

Case-Control Study Examining the Composition of the Gut Microbiome in Individuals With and Without Immune-Mediated Dry Eye.

PURPOSE: Gut microbiome alterations have been associated with various autoimmune diseases. There are limited data, however, on relationships between gut dysbiosis and immune-related dry eye (DE). Our aim was to compare the gut microbiome composition of individuals with early and late markers of Sjögren syndrome (SS) with controls without DE. METHODS: We compared 20 individuals with positive early markers [antisalivary protein 1 (SP1), antiparotid secretory protein (PSP), anticarbonic anhydrase 6 (CA6) IgG, IgA, and IgM, n = 19)], or late markers (anti-Ro/SS-A and anti-La/SS-B, n = 1) of SS with no comorbid autoimmune diagnoses and 20 age-matched and sex-matched controls. Collected stool samples underwent deep RNA sequencing. The main outcomes measured included gut microbiome composition and diversity. RESULTS: A total of 20 cases [Dry Eye Questionnaire-5 15.2 ± 3.4, Ocular Surface Disease Index 55.1 ± 22.8, and Schirmer 7.1 ± 5.2 mm] were compared with 20 controls (Dry Eye Questionnaire-5 4.8 ± 3.8, Ocular Surface Disease Index 14.2 ± 12.3, and Schirmer 20.4 ± 9.2 mm). No differences were observed in α-diversity (P = 0.97) or overall community structure (P = 0.62). Between groups, 32 species were differentially abundant (P < 0.01). Among cases, 27 were relatively more abundant, including 10 Lactobacillus and 4 Bifidobacterium species. A relative depletion of 5 species was found in cases compared with controls, notably Fusobacterium varium and Prevotella stercorea. CONCLUSIONS: Differences in gut microbiome composition were found in individuals with mostly early markers of SS compared with controls. However, their clinical significance to DE manifestations remains unclear. Further studies are needed to elucidate the role of gut dysbiosis on immune dysregulation and disease activity in the various forms of immune-mediated DE.

Anti-Virulence Properties of Plant Species: Correlation between In Vitro Activity and Efficacy in a Murine Model of Bacterial Infection.

Several plant extracts exhibit anti-virulence properties due to the interruption of bacterial quorum sensing (QS). However, studies on their effects at the preclinical level are scarce. Here, we used a murine model of abscess/necrosis induced by Pseudomonas aeruginosa to evaluate the anti-pathogenic efficacy of 24 plant extracts at a sub-inhibitory concentration. We analyzed their ability to inhibit QS-regulated virulence factors such as swarming, pyocyanin production, and secretion of the ExoU toxin via the type III secretion system (T3SS). Five of the seven extracts with the best anti-pathogenic activity reduced ExoU secretion, and the extracts of Diphysa americana and Hibiscus sabdariffa were identified as the most active. Therefore, the abscess/necrosis model allows identification of plant extracts that have the capacity to reduce pathogenicity of P. aeruginosa. Furthermore, we evaluated the activity of the plant extracts on Chromobacterium violaceum. T3SS (ΔescU) and QS (ΔcviI) mutant strains were assessed in both the abscess/necrosis and sepsis models. Only the ΔescU strain had lower pathogenicity in the animal models, although no activity of plant extracts was observed. These results demonstrate differences between the anti-virulence activity recorded in vitro and pathogenicity in vivo and between the roles of QS and T3S systems as virulence determinants.

Taxonomic revision of the Mesoamerican genus Spathacanthus (Justicieae, Acanthoideae, Acanthaceae).

Spathacanthus is a Mesoamerican genus that occurs in tropical and temperate regions from southern Mexico to Costa Rica; its taxonomy has not been updated for two decades. In view of the fact that a new species has been discovered and that the interspecific affinities in this genus have not been addressed to date, the present study aims to revise the genus Spathacanthus. Specimens of plants of this genus collected from across the distribution range and deposited in herbaria and digital databases were reviewed. In parallel, a cladistic analysis was carried out, based on morphological characters in order to examine relationships between species. Four species of Spathacanthus were recognised: one endemic to Costa Rica, another micro-endemic to Veracruz in Mexico, one more restricted to the forests of Mexico and Guatemala and the last one more widely distributed. Reflecting the previously limited knowledge of the group, many of the specimens that we studied had been misidentified. A key to differentiate these species is provided, supplemented with photographs, drawings and other illustrations, morphological descriptions, synonymy and ecological data. Results, presented here, extend the distribution range of some taxa and a distribution map is presented. The cladistic analysis recovered the genus as monophyletic, showing that S. hoffmannii and S. hahnianus are sister taxa and S. magdalenae was found to be more closely related to S. parviflorus. These plants are vulnerable to degradation and habitat loss.

Chronic sucralose consumption induces elevation of serum insulin in young healthy adults: a randomized, double blind, controlled trial.

BACKGROUND: Non-nutritive sweeteners (NNS) are widely consumed by humans due to their apparent innocuity, especially sucralose. However, several studies link sucralose consumption to weight gain and metabolic derangements, although data are still contradictory. OBJECTIVE: To determine the effect of acute and chronic consumption of sucralose on insulin and glucose profiles in young healthy adults. MATERIAL AND METHODS: This was a randomized, parallel, double-blind, placebo-controlled trial conducted in healthy young adults from 18 to 35 years old, without insulin resistance. A hundred thirty seven participants were randomized into three groups: a) volunteers receiving 48 mg sucralose, b) volunteers receiving 96 mg sucralose, and c) controls receiving water as placebo. All participants underwent a 3-h oral glucose tolerance test (OGTT) preceded by consuming sucralose or placebo 15 min before glucose load, at two time points: week zero (Wk0) and week ten (Wk10). Serum insulin and glucose were measured every 15 min during both OGTTs. RESULTS: Compared to Wk0, consumption of sucralose for 10 weeks provoked 1) increased insulin concentrations at 0 min (7.5 ± 3.4 vs 8.8 ± 4.1 µIU/mL; p = 0.01), 30 min (91.3 ± 56.2 vs 110.1 ± 49.4 µIU/mL; p = 0.05), 105 min (47.7 ± 24.4 vs 64.3 ± 48.2 µIU/mL; p = 0.04) and 120 min (44.8 ± 22.1 vs 63.1 ± 47.8 µIU/mL; p = 0.01) in the 48 mg sucralose group; 2) increased blood glucose at - 15 min (87.9 ± 4.6 vs 91.4 ± 5.4 mg/dL; p = 0.003), 0 min (88.7 ± 4 vs 91.3 ± 6 mg/dL; p = 0.04) and 120 min (95.2 ± 23.7 vs 106.9 ± 19.5 mg/dL; p = 0.009) in the 48 mg sucralose group; 3) increased area under the curve (AUC) of insulin in both 48 and 96 mg sucralose groups (9262 vs 11,398; p = 0.02 and 6962 vs 8394; p = 0.12, respectively); and 4) reduced Matsuda index in the 48 mg sucralose group (6.04 ± 3.19 vs 4.86 ± 2.13; p = 0.01). CONCLUSIONS: These data show that chronic consumption of sucralose can affect insulin and glucose responses in non-insulin resistant healthy young adults with normal body mass index (between 18.5 and 24.9 kg/m2), however, the effects are not consistent with dose; further research is required. CLINICAL TRIAL REGISTRY: NCT03703141.

AP-1 and Mitf interact with NFATc1 to stimulate cathepsin K promoter activity in osteoclast precursors.

Cathepsin K (CTSK) is a secreted protease that plays an essential role in osteoclastic bone resorption and osteoporotic bone loss. We have previously shown that activator protein 1 (AP-1) stimulates CTSK promoter activity and that proximal nuclear factor of activated T cells cytoplasmic 1 (NFATc1)-binding sites play a major role in the stimulation of CTSK gene expression by receptor activator of NFκB ligand (RANKL). In the present study, we have extended these observations and further dissected the effects of transcription factors involved in the regulation of CTSK gene expression. Our aim was to investigate the cooperative interplay among transcription factors AP-1, microphthalmia-associated transcription factor (Mitf), and NFATc1, and the consequent regulatory effects on CTSK transcription. Experiments were carried out in RAW 264.7 cells, which can be readily differentiated to osteoclasts upon RANKL stimulation. Our data show that AP-1, Mitf, and NFATc1 are capable of independently stimulating CTSK promoter activity. A combination of any two factors further enhances CTSK promoter activity, with the combination of AP-1 (c-fos/c-jun) and NFATc1 inducing the largest increase. We further identify a synergistic effect when all three factors cooperate intimately at the proximal promoter region, yielding maximal transcriptional upregulation of the CTSK promoter. RANKL induces temporal localization of AP-1 and NFATc1 to the CTSK promoter. These results suggest that the interaction of multiple transcription factors mediate a maximal response to RANKL-induced CTSK gene expression.

Chronic vitamin D insufficiency impairs physical performance in C57BL/6J mice.

Vitamin D insufficiency (serum 25-OH vitamin D < 30 ng/ml) affects 70-80% of the general population, yet the long-term impacts on physical performance and the progression of sarcopenia are poorly understood. We therefore followed 6-month-old male C57BL/6J mice (n=6) consuming either sufficient (STD, 1000 IU) or insufficient (LOW, 125 IU) vitamin D3/kg chow for 12 months (equivalent to 20-30 human years). LOW supplemented mice exhibited a rapid decline of serum 25-OH vitamin D levels by two weeks that remained between 11-15 ng/mL for all time points thereafter. After 12 months LOW mice displayed worse grip endurance (34.6 ± 14.1 versus 147.5 ± 50.6 seconds, p=0.001), uphill sprint speed (16.0 ± 1.0 versus 21.8 ± 2.4 meters/min, p=0.0007), and stride length (4.4 ± 0.3 versus 5.1 ± 0.3, p=0.002). LOW mice also showed less lean body mass after 8 months (57.5% ± 5.1% versus 64.5% ± 4.0%, p=0.023), but not after 12 months of supplementation, as well as greater protein expression of atrophy pathway gene atrogin­1. Additionally, microRNA sequencing revealed differential expression of mIR­26a in muscle tissue of LOW mice. These data suggest chronic vitamin D insufficiency may be an important factor contributing to functional decline and sarcopenia.