Metabolic and fecal microbial changes in adult fetal growth restricted mice.

BACKGROUND: Fetal growth restriction (FGR) increases risk for development of obesity and type 2 diabetes. Using a mouse model of FGR, we tested whether metabolic outcomes were exacerbated by high-fat diet challenge or associated with fecal microbial taxa. METHODS: FGR was induced by maternal calorie restriction from gestation day 9 to 19. Control and FGR offspring were weaned to control (CON) or 45% fat diet (HFD). At age 16 weeks, offspring underwent intraperitoneal glucose tolerance testing, quantitative MRI body composition assessment, and energy balance studies. Total microbial DNA was used for amplification of the V4 variable region of the 16 S rRNA gene. Multivariable associations between groups and genera abundance were assessed using MaAsLin2. RESULTS: Adult male FGR mice fed HFD gained weight faster and had impaired glucose tolerance compared to control HFD males, without differences among females. Irrespective of weaning diet, adult FGR males had depletion of Akkermansia, a mucin-residing genus known to be associated with weight gain and glucose handling. FGR females had diminished Bifidobacterium. Metabolic changes in FGR offspring were associated with persistent gut microbial changes. CONCLUSION: FGR results in persistent gut microbial dysbiosis that may be a therapeutic target to improve metabolic outcomes. IMPACT: Fetal growth restriction increases risk for metabolic syndrome later in life, especially if followed by rapid postnatal weight gain. We report that a high fat diet impacts weight and glucose handling in a mouse model of fetal growth restriction in a sexually dimorphic manner. Adult growth-restricted offspring had persistent changes in fecal microbial taxa known to be associated with weight, glucose homeostasis, and bile acid metabolism, particularly Akkermansia, Bilophilia and Bifidobacteria. The gut microbiome may represent a therapeutic target to improve long-term metabolic outcomes related to fetal growth restriction.

Angiogenic and Inflammatory microRNA Regulation in a Mouse Model of Fetal Growth Restriction.

INTRODUCTION: Fetal growth restriction (FGR) is associated with impaired angiogenesis and chronic inflammation. MicroRNAs (miRs) are short noncoding RNAs that regulate gene expression at the post-transcriptional level by targeting messenger RNA (mRNA) for degradation or by suppressing translation. We hypothesize that dysregulation of miR-15b, an antiangiogenic miR, and miR-146a, an anti-inflammatory miR, are associated with the FGR's pathogenesis. METHODS: Pregnant mice were provided ad libitum access to food between E1 and E8. From E9-E18, dams received either a 50% caloric restricted diet (FGR) or continued ad libitum access (controls). Placentas were harvested at E18.5 and total RNA was extracted. Gene expression levels of miRs and mRNAs were compared between FGR and control placentas. RESULTS: Placentas affected by FGR demonstrated increased expression of miR-15b. Vascular endothelial growth factor alpha, which is downregulated in response to increased levels of miR-15b, was suppressed. The anti-inflammatory miR, miR-146a, was downregulated, resulting in upregulation of proinflammatory (IL-6, IL-8, and NFkB1) and oxidative stress (HIF-1α, SOD2, and Nox2) mediators. CONCLUSIONS: Aberrant angiogenesis and chronic inflammation seen in FGR appear to be associated with dysregulated miR-15b and miR-146a gene expression, respectively. This observation suggests these miRs play a post-transcriptional regulatory role in FGR, providing an insight into possible therapeutic targets.

Why honeybees are poor pollinators of a mass-flowering plant: Experimental support for the low pollen quality hypothesis.

PREMISE: Honeybees dominate the flower-visitor assemblages of many plant species, yet their efficiency in terms of the quality of pollen delivered to stigmas is largely unknown. We investigated why honeybees are poor pollinators of Aloe ferox, a self-incompatible succulent treelet with large numbers of flowers. Honeybees are very frequent visitors to flowers of this species, yet contribute very little to seed production. METHODS: We assessed pollen loads on honeybees, studied their visitation behavior, selectively excluded birds from plants to determine direct effects of bees on pollen deposition, seed set, and ovule abortion, and used a novel "split-pollinator" method to test whether honeybees deposit mainly low-quality self pollen. For the latter, we captured honeybees, and with their existing pollen loads, used them to either pollinate virgin flowers on the plant on which they were caught or to pollinate virgin flowers on different plants. RESULTS: Honeybees cumulatively deposit as much pollen on stigmas as do birds, but our experiments showed that the pollen deposited by honeybees is mostly low-quality self pollen that leads to substantial ovule discounting and depressed seed set. CONCLUSIONS: Lack of movement among A. ferox plants during individual honeybee foraging bouts is the most likely explanation for their deposition of low-quality self pollen on stigmas. The "split-pollinator" method is a simple and cost-effective technique to test the quality of pollination.

Pulmonary implications of acetaminophen exposures independent of hepatic toxicity.

Both preclinical and clinical studies have demonstrated that exposures to acetaminophen (APAP) at levels that cause hepatic injury cause pulmonary injury as well. However, whether exposures that do not result in hepatic injury have acute pulmonary implications is unknown. Thus, we sought to determine how APAP exposures at levels that do not result in significant hepatic injury impact the mature lung. Adult male ICR mice (8-12 wk) were exposed to a dose of APAP known to cause hepatotoxicity in adult mice [280 mg/kg, intraperitoneal (ip)], as well as a lower dose previously reported to not cause hepatic injury (140 mg/kg, ip). We confirm that the lower dose exposures did not result in significant hepatic injury. However, like high dose, lower exposure resulted in increased cellular content of the bronchoalveolar lavage fluid and induced a proinflammatory pulmonary transcriptome. Both the lower and higher dose exposures resulted in measurable changes in lung morphometrics, with the lower dose exposure causing alveolar wall thinning. Using RNAScope, we were able to detect dose-dependent, APAP-induced pulmonary Cyp2e1 expression. Finally, using FLIM we determined that both APAP exposures resulted in acute pulmonary metabolic changes consistent with mitochondrial overload in lower doses and a shift to glycolysis at a high dose. Our findings demonstrate that APAP exposures that do not cause significant hepatic injury result in acute inflammatory, morphometric, and metabolic changes in the mature lung. These previously unreported findings may help explain the potential relationship between APAP exposures and pulmonary-related morbidity.

On the adaptive value of monomorphic versus dimorphic enantiostyly in Solanum rostratum.

Background and Aims: Enantiostyly is a reproductive system with heteromorphic flowers characterized by asymmetrical deflection of the style, either to the left or to the right of the floral axis. There are two types of enantiostyly. In monomorphic enantiostyly, plants produce the two types of flowers in the same individual. Dimorphic enantiostyly is restricted to only seven species and their populations consist of individuals producing either the right or the left flower type. It is hypothesized that the dimorphic form is derived from monomorphic ancestors because it functions as an outcrossing mechanism. We tested this latter hypothesis and investigated if monomorphic enantiostyly is resistant to invasion by individuals with dimorphic enantiostyly, because it functions as a reproductive assurance mechanism. Methods: To determine the conditions favouring the invasion of dimorphic enantiostyly, measurements of reproductive success and outcrossing rates in 15 natural flowering patches of Solanum rostratum were made. To test if monomorphic enantiostyly provides a reproductive assurance mechanism, experimental plants with either manually created dimorphic or natural monomorphic reproductive systems were exposed to two different pollination scenarios (flower density treatments), and reproductive success and outcrossing rates were measured. Key Results: Naturally flowering patches experienced severe pollination limitation, showed marked differences in reproductive success and had relatively high outcrossing rates. Plants in the experimental patches also showed pollination limitation and high outcrossing rates. Individuals with dimorphic enantiostyly expressed higher reproductive and outcrossing advantages under high-density conditions. These advantages disappeared in the low-density treatment, where the monomorphic form attained a higher reproductive success and no differences in outcrossing rates were detected. Conclusions: Monomorphic enantiostyly should be resistant to invasion of the dimorphic form because the prevalent ecological conditions favour the maintenance of geitonogamous individuals that are able to take advantage of ecological heterogeneity and generalized pollination limitation.

Generalist birds outperform specialist sunbirds as pollinators of an African Aloe.

Bird pollination systems are dominated by specialist nectarivores, such as hummingbirds in the Americas and sunbirds in Africa. Opportunistic (generalist) avian nectarivores such as orioles, weavers and bulbuls have also been implicated as plant pollinators, but their effectiveness as agents of pollen transfer is poorly known. Here, we compare the single-visit effectiveness of specialist and opportunistic avian nectarivores as pollinators of Aloe ferox, a plant that relies almost exclusively on birds for seed production. We found that the number of pollen grains on stigmas of flowers receiving single visits by opportunistic avian nectarivores was approximately threefold greater than on those receiving single visits by specialist sunbirds and about twofold greater than on those that received single visits by honeybees. The number of pollen grains on stigmas of flowers visited by sunbirds was similar to that on stigmas of unvisited flowers. These results show that opportunistic birds are highly effective pollinators of A. ferox, supporting the idea that some plants are specialized for pollination by opportunistic birds.

Effects of ketamine on the fetal transcriptomic response to umbilical cord occlusion: comparison with hypoxic hypoxia in the cerebral cortex.

KEY POINTS: The cerebral response to fetal asphyxia is characterized by an upregulation of nucleic acid and chromatin modification processes, as well as a downregulation of metabolic processes at 1 h post-umbilical cord occlusion (UCO). Twenty-four hours post UCO, there was an upregulation of metabolic processes and protein modifications. UCO did not alter bacterial gene expression levels, nor did it produce a robust inflammatory response compared to maternal hypoxia. The administration of ketamine produced minimal effects on the fetal response to UCO in the cerebral cortex. ABSTRACT: Umbilical cord occlusion (UCO) is known to cause neurological disorders in the neonate. Previously, we have reported that hypoxic hypoxia (HH) stimulates the appearance of bacteria in the fetal brain and upregulates the expression of inflammatory markers in fetal cerebral cortex (CTX) and also that ketamine attenuates these responses. In the present study, we aimed to test the hypothesis that UCO, similar to HH, produces an inflammatory response in the fetal CTX and also that treatment with ketamine reduces these effects. In chronically instrumented fetal sheep (∼125 days), 30 min of partial UCO decreased fetal PaO2 levels by ∼50%. Half of the fetuses received ketamine (3 mg kg-1 ) 10 min prior to UCO (n = 4 per group). Fetal brains were collected 1 and 24 h after the experiment and mRNA was extracted and hybridized for microarray analyses. Differentially-expressed genes were analysed for significant association with gene ontologies and pathways. After 1 h, UCO upregulated nucleic acid processing and chromatin modification and downregulated metabolic processes compared to control. After 24 h, UCO upregulated metabolic and protein modification processes. Ketamine produced minimal effects. UCO did not alter the abundance of bacterial DNA in fetal brain, nor did it upregulate inflammation pathways compared to HH. We conclude that UCO produced time-dependent responses that did not include bacterial invasion or upregulation of inflammation pathways in fetal CTX. This contrasts with the response to HH, which resulted in the appearance of bacteria in the CTX and upregulated inflammation pathways. These responses in fetal CTX to oxygen deprivation are therefore modified by the maternal or placental response to the stimulus.

Tropical plant supplementation effects on the performance and parasite burden of goats.

OBJECTIVE: Examine the effects of supplementing bahiagrass hay (BG) with potentially anthelmintic quantities of hays of perennial peanut (PEA) or sericea lespedeza (LES) or seeds of velvet bean (Mucuna pruriens L.; MUC) or papaya (PAP) on the intake and nutritive value (Experiment 1), and the performance and parasite burden (Experiment 2) of goats. METHODS: In Experiment 1, 38 male goats (27.4±5.7 kg body weight) were randomly assigned to each of 5 treatments: i) BG alone and BG plus; ii) PEA; iii) LES; iv) MUC; and v) PAP. Goats were fed for ad libitum consumption and adapted to the diets for 14 d followed by 7 d of measurement. The PEA, LES, MUC (50%, 50%, and 10% of the diet dry matter [DM], respectively), and PAP (forced-fed at 10 g/d) were fed at rates that would elicit anthelmintic effects. In Experiment 2, goats remained in the same treatments but were allocated to 15 pens (3 pens per treatment) from d 22 to 63. All goats were infected with parasites by grazing an infected bahiagrass pasture from 0800 to 1500 h daily and then returned to the pens. RESULTS: Dry matter intake tended to be greater in goats fed PEA and LES than those fed BG (757 and 745 vs 612 g/d, respectively). Digestibility of DM (59.5% vs 54.9%) and organic matter (60.8% vs 56.0%) were greater in goats fed MUC vs BG, respectively. In Experiment 2, feeding PAP, LES, and PEA to goats reduced nematode fecal egg counts by 72%, 52%, and 32%, reduced abomasal adult worm counts by 78%, 52%, and 42%, and decreased plasma haptoglobin concentrations by 42%, 40%, and 45% relative to feeding BG alone, respectively. CONCLUSION: Supplementation with PEA, LES, and PAP decreased the parasite burden of goats but did not increase their performance. PAP was the most effective anthelmintic supplement.

Ketamine suppresses hypoxia-induced inflammatory responses in the late-gestation ovine fetal kidney cortex.

Acute fetal hypoxia is a form of fetal stress that stimulates renal vasoconstriction and ischaemia as a consequence of the physiological redistribution of combined ventricular output. Because of the potential ischaemia-reperfusion injury to the kidney, we hypothesized that it would respond to hypoxia with an increase in the expression of inflammatory genes, and that ketamine (an N-methyl-D-aspartate receptor antagonist) would reduce or block this response. Hypoxia was induced for 30 min in chronically catheterized fetal sheep (125 ± 3 days), with or without ketamine (3 mg kg(-1)) administered intravenously to the fetus 10 min prior to hypoxia. Gene expression in fetal kidney cortex collected 24 h after the onset of hypoxia was analysed using ovine Agilent 15.5k array and validated with qPCR and immunohistochemistry in four groups of ewes: normoxic control, normoxia + ketamine, hypoxic control and hypoxia + ketamine (n = 3-4 per group). Significant differences in gene expression between groups were determined with t-statistics using the limma package for R (P ≤ 0.05). Enriched biological processes for the 427 upregulated genes were immune and inflammatory responses and for the 946 downregulated genes were metabolic processes. Ketamine countered the effects of hypoxia on upregulated immune/inflammatory responses as well as the downregulated metabolic responses. We conclude that our transcriptomics modelling predicts that hypoxia activates inflammatory pathways and reduces metabolism in the fetal kidney cortex, and ketamine blocks or ameliorates this response. The results suggest that ketamine may have therapeutic potential for protection from ischaemic renal damage.

Transcriptomics of the fetal hypothalamic response to brachiocephalic occlusion and estradiol treatment.

Estradiol (E2) is a well-known modulator of fetal neuroendocrine activity and has been proposed as a critical endocrine signal readying the fetus for birth and postnatal life. To investigate the modulatory role of E2 on fetal stress responsiveness and the response of the fetal brain to asphyxic stress, we subjected chronically catheterized fetal sheep to a transient (10 min) brachiocephalic artery occlusion (BCO) or sham occlusion. Half of the fetuses received subcutaneous pellets that increased plasma E2 concentrations within the physiological range. Hypothalamic mRNA was analyzed using the Agilent 8x15k ovine array (019921), processed and annotated as previously reported by our laboratory. Analysis of the data by ANOVA revealed that E2 differentially regulated (DR) 561 genes, and BCO DR 894 genes compared with control and E2+BCO DR 1,153 genes compared with BCO alone (all P < 0.05). E2 upregulated epigenetic pathways and downregulated local steroid biosynthesis but did not significantly involve genes known to directly respond to the estrogen receptor. Brachiocephalic occlusion upregulated kinase pathways as well as genes associated with lymphocyte infiltration into the brain and downregulated neuropeptide synthesis. E2 upregulated immune- and apoptosis-related pathways after BCO and reduced kinase and epigenetic pathway responses to the BCO. Responses to BCO are different from responses to hypoxic hypoxia suggesting that mechanisms of responses to these two forms of brain hypoxia are distinct. We conclude that cerebral ischemia caused by BCO might stimulate lymphocyte infiltration into the brain and that this response appears to be modified by estradiol.

Dysregulation of miRNA-mRNA expression in fetal growth restriction in a caloric restricted mouse model.

Fetal growth restriction (FGR) is associated with aberrant placentation and accounts for a significant proportion of perinatal deaths. microRNAs have been shown to be dysregulated in FGR. The purpose of this study was to determine microRNA-regulated molecular pathways altered using a caloric restricted mouse model of FGR. Pregnant mice were subjected to a 50% caloric restricted diet beginning at E9. At E18.5, RNA sequencing of placental tissue was performed to identify differences in gene expression between caloric restricted and control placentas. Significant differences in gene expression between caloric restricted and control placentas were observed in 228 of the 1546 (14.7%) microRNAs. Functional analysis of microRNA-mRNA interactions demonstrated enrichment of several biological pathways with oxidative stress, apoptosis, and autophagy pathways upregulated and angiogenesis and signal transduction pathways downregulated. Ingenuity pathway analysis also suggested that ID1 signaling, a pathway integral for trophoblast differentiation, is also dysregulated in caloric restricted placentas. Thus, a maternal caloric restriction mouse model of FGR results in aberrant microRNA-regulated molecular pathways associated with angiogenesis, oxidative stress, signal transduction, apoptosis, and cell differentiation. As several of these pathways are dysregulated in human FGR, our findings suggest that this model may provide an excellent means to study placental microRNA derangements seen in FGR.

Stories told by corals, algae, and sea-urchins in a Mesoamerican coral reef: degradation trumps succession.

Understanding the mechanisms that allow the permanence of coral reefs and the constancy of their characteristics is necessary to alleviate the effects of chronic environmental changes. After a disturbance, healthy coral reefs display trajectories that allow regaining coral cover and the establishment of framework building corals. Through a comparative approach, in a patch reef partially affected by a ship grounding, we analyzed the successional trajectories in affected and unaffected sectors. Fleshy algae (which do not promote the recruitment of corals) dominated the reef surface irrespective of the impact of the ship grounding incident. Acropora species had near-zero contributions to community structure, whereas non-framework building corals like Porites sp. had a slightly higher recruitment. Cover of coral and calcareous crustose algae decreased over time, and neither the latter nor adult coral colonies had any effect on the occurrence probabilities of small corals. Sea urchin (Diadema antillarum) densities were generally low, and thus unlikely to contribute to reverting algal dominance. The successional trajectories of the community in the impacted and non-impacted sectors of the coral patch reef agree with the inhibition successional model, leading to the development of a degraded state dominated by fleshy algae. It is probable that the stability and resilience of this degraded state are high due to the ability of fleshy algae to monopolize space, along with low coral recovery potential.

Changes in the community structure of stony corals in the southern Mexican Caribbean.

The Mexican Caribbean coral reef ecosystem has endured the effects of global and regional stressors and, recently, the massive arrivals of the free-living, floating brown algae Sargassum spp. This study aimed to evaluate spatiotemporal changes in the stony coral community structure in the southern Mexican Caribbean by a temporal comparison of live coral cover and colony density using a data set collected in 2008-2009 and a recent survey in 2021 within a Protected Natural Area. A multivariate analysis approach was used to reveal spatiotemporal changes in coral cover and colony densities. Coral cover ranged from 6.9 to 8.9% in 2008-2009 to 6.5% in 2021, the lowest values recorded for the area. Coral colony density ranged from 0.68 to 0.78 colonies m-1 in 2008-2009 to 0.68 colonies m-1 in 2021. The present results appear to represent subtle changes during the last decade.

Traumatic scalp arteriovenous fistula post capillary implantation successfully treated using PHIL embolic agent.

Background: A traumatic arteriovenous fistula of the scalp due to hair transplantation (AVFHT) is a rare fistulous communication between branches of the arteries and draining veins in the scalp's subcutaneous tissue. Its incidence is unknown and its clinical manifestations may range from a pulsatile mass to seldom epilepsy. Surgery and interventional approaches (percutaneous and endovascular embolization) using coils and embolic agents such as Onyx have been used as treatment options. The authors report a rare case of an AVFHT successfully treated through percutaneous and endovascular embolization using coils and precipitating hydrophobic injectable liquid (PHIL) embolic agent. This is possibly the first reported case using PHIL embolic agent to treat an AVFHT. Case Description: The patient presented with a painful and disabling scalp swelling in the right parieto-occipital region 2 years after a hair transplant in 2011. A computed tomography angiography showed an arteriovenous fistula between branches of the right superficial temporal artery and branches of the right occipital artery to the right superficial temporal vein that was successfully embolized using coils and PHIL. The patient was discharged after a smooth recovery and 1 month later remained healthy. Conclusion: Percutaneous and endovascular embolization using PHIL embolic agent can be an alternative treatment for AVFHT.

APAP-Induced IκBß/NFκB Signaling Drives Hepatic Il6 Expression and Associated Sinusoidal Dilation.

Acetaminophen (APAP) overdose results in high morbidity and mortality, with limited treatment options. Increased understanding of the cellular signaling pathways activated in response to toxic APAP exposure is needed to provide insight into novel therapeutic strategies. Toxic APAP exposure induces hepatic nuclear factor kappa B (NFκB) activation. NFκB signaling has been identified to mediate the proinflammatory response but also induces a prosurvival and regenerative response. It is currently unknown whether potentiating NFkB activation would be injurious or advantageous after APAP overdose. The NFκB inhibitory protein beta (IκBß) dictates the duration and degree of the NFκB response following exposure to oxidative injuries. Thus, we sought to determine whether IκBß/NFκB signaling contributes to APAP-induced hepatic injury. At late time points (24 h) following toxic APAP exposures, mice expressing only IκBß knock-in mice (AKBI mice) exhibited increased serologic evidence of hepatic injury. This corresponded with increased histologic injury, specifically related to sinusoidal dilatation. When compared with wild type mice, AKBI mice demonstrated sustained hepatic nuclear translocation of the NFκB subunits p65 and p50, and enhanced NFκB target gene expression. This included increased expression of interleukin-6 (Il-6), a known contributor to hepatic sinusoidal dilation. This transcriptional response corresponded with increased plasma protein content of Il-6, as well as increased activation of signal transducer and activator of transcription 3.

[Epidemiological characteristics of workers with COVID-19 from the Instituto Mexicano del Seguro Social]. / Características epidemiológicas de trabajadores con COVID-19 del Instituto Mexicano del Seguro Social.

Background: ¿In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused an outbreak of the respiratory disease called COVID-19, in Wuhan, China. At the end of February 2020, it was detected in Mexico the first case of COVID-19. With this disease, chronic degenerative diseases are decisive for comorbidity to continue increasing. Objective: To know the epidemiological characteristics and comorbidity in workers sick with COVID-19 from the Veracruz Norte Regional Deconcentrated Administrative Operation Body, from the Mexican Institute for Social Security (Instituto Mexicano del Seguro Social, IMSS). Material and methods: Descriptive, cross-sectional study, which included 228 COVID-19 patients, who were IMSS workers. Variables such as age, gender, as well as medical unit, contractual category, comorbidities, etc., were analyzed and were taken from April to June 2020 from the Online Notification System for Epidemiological Surveillance (SINOLAVE) database. It was used descriptive statistics, and Pearson's chi-squared, with a p < 0.05. Results: 228 patients were analyzed. The nursing staff was the one with the highest prevalence with 101 patients (44.3%). Comorbidities such as obesity in the foreground, with 27 patients (11.8%), and diabetes mellitus alone with 15 patients (6.6%), and as a group, along with arterial hypertension, obesity and being a chronic smoker in 22 patients (9.6%) were the most frequent. Conclusions: The nursing staff predominated; the prevalent comorbidities were obesity, diabetes mellitus and arterial hypertension.

Introducción: en diciembre de 2019, el coronavirus 2 causante del síndrome respiratorio agudo severo (SARS-CoV-2) provocó un brote en Wuhan, China, de la enfermedad respiratoria denominada COVID-19. A finales de febrero de 2020 se detectó en México el primer caso de COVID-19. Con esta enfermedad, las enfermedades crónicas degenerativas son determinantes para que la comorbilidad continúe en aumento. Objetivo: conocer las características epidemiológicas y la comorbilidad en trabajadores enfermos de COVID-19 del Órgano de Operación Administrativa Desconcentrada Estatal Veracruz Norte, del Instituto Mexicano del Seguro Social (IMSS). Material y métodos: estudio descriptivo y transversal que incluyó a 228 pacientes de COVID-19, trabajadores del IMSS. Se analizaron variables como edad, género, así como unidad médica, categoría contractual, comorbilidades, etcétera, las cuales se tomaron de abril a junio de 2020 de la base del Sistema de Notificación en Línea para la Vigilancia Epidemiológica (SINOLAVE). Se empleó estadística descriptiva y chi cuadrada de Pearson, con una p < 0.05. Resultados: se analizaron 228 pacientes. El personal de enfermería fue el de mayor prevalencia, con 101 pacientes (44.3%). Las comorbilidades más frecuentes fueron la obesidad en primer plano, con 27 pacientes (11.8%), y la diabetes mellitus por sí sola con 15 (6.6%), y en conjunto, con hipertensión arterial, obesidad y ser fumador crónico se presentaron en 22 pacientes (9.6 %). Conclusiones: predominó el personal de enfermería; las comorbilidades prevalentes fueron la obesidad, la diabetes mellitus y la hipertensión arterial.

The Acute Hepatic NF-κB-Mediated Proinflammatory Response to Endotoxemia Is Attenuated in Intrauterine Growth-Restricted Newborn Mice.

Intrauterine growth restriction (IUGR) is a relevant predictor for higher rates of neonatal sepsis worldwide and is associated with an impaired neonatal immunity and lower immune cell counts. During the perinatal period, the liver is a key immunological organ responsible for the nuclear factor kappa B (NF-κB)-mediated innate immune response to inflammatory stimuli, but whether this role is affected by IUGR is unknown. Herein, we hypothesized that the newborn liver adapts to calorie-restriction IUGR by inducing changes in the NF-κB signaling transcriptome, leading to an attenuated acute proinflammatory response to intraperitoneal lipopolysaccharide (LPS). We first assessed the hepatic gene expression of key NF-κB factors in the IUGR and normally grown (NG) newborn mice. Real-time quantitative PCR (RT-qPCR) analysis revealed an upregulation of both IκB proteins genes (Nfkbia and Nfkbib) and the NF-κB subunit Nfkb1 in IUGR vs. NG. We next measured the LPS-induced hepatic expression of acute proinflammatory genes (Ccl3, Cxcl1, Il1b, Il6, and Tnf) and observed that the IUGR liver produced an attenuated acute proinflammatory cytokine gene response (Il1b and Tnf) to LPS in IUGR vs. unexposed (CTR). Consistent with these results, LPS-exposed hepatic tumor necrosis factor alpha (TNF-α) protein concentrations were lower in IUGR vs. LPS-exposed NG and did not differ from IUGR CTR. Sex differences at the transcriptome level were observed in the IUGR male vs. female. Our results demonstrate that IUGR induces key modifications in the NF-κB transcriptomic machinery in the newborn that compromised the acute proinflammatory cytokine gene and protein response to LPS. Our results bring novel insights in understanding how the IUGR newborn is immunocompromised due to fundamental changes in NF-κB key factors.

Neonatal Selenoenzyme Expression Is Variably Susceptible to Duration of Maternal Selenium Deficiency.

Maternal selenium (Se) deficiency is associated with decreased neonatal Se levels, which increases the risk for neonatal morbidities. There is a hierarchy to selenoprotein expression after Se deficiency in adult rodents, depending on the particular protein and organ evaluated. However, it is unknown how limited Se supply during pregnancy impacts neonatal selenoprotein expression. We used an Se-deficient diet to induce perinatal Se deficiency (SeD), initiated 2-4 weeks before onset of breeding and continuing through gestation. Neonatal plasma, liver, heart, kidney, and lung were collected on the day of birth and assessed for selenoproteins, factors required for Se processing, and non-Se containing antioxidant enzymes (AOE). Maternal SeD reduced neonatal circulating and hepatic glutathione peroxidase (GPx) activity, as well as hepatic expression of Gpx1 and selenophosphate synthetase 2 (Sps2). In contrast, the impact of maternal SeD on hepatic thioredoxin reductase 1, hepatic non-Se containing AOEs, as well as cardiac, renal, and pulmonary GPx activity, varied based on duration of maternal exposure to SeD diet. We conclude that the neonatal liver and circulation demonstrate earlier depletion in selenoenzyme activity after maternal SeD. Our data indicate that prolonged maternal SeD may escalate risk to the neonate by progressively diminishing Se-containing AOE across multiple organs.

Food Reward Chemistry Explains a Novel Pollinator Shift and Vestigialization of Long Floral Spurs in an Orchid.

During the evolutionary history of flowering plants, transitions between pollinator groups (pollinator shifts) have been frequent,1 and contributed to the spectacular radiation of angiosperms.2 Although the evolution of floral traits during pollinator shifts has been studied in real time under controlled laboratory conditions,3 it is challenging to study in nature and therefore poorly understood.4-7 Using a comparative, multidisciplinary approach, we dissect the evolution of floral traits during a pollinator shift in the long-spurred African orchid Satyrium longicauda. Phylogenetic analysis and ecological experiments revealed a shift from moth- to oil-collecting bee pollination. Remarkably, flowers of the bee-pollinated form are similar in morphology, color, and overall volatile chemistry to those of moth-pollinated forms, but differ in having spurs that are mostly devoid of nectar, and have an elevated presence of the oil-derived compound diacetin, which oil-collecting bees use as a cue for oil presence.8 Experiments demonstrated that long spurs are critical for pollination of a moth-pollinated form, but are not needed for pollination of the bee-pollinated form. We conclude that the pollinator shift in Satyrium was mediated by a switch in chemistry of the pollinator reward. The ancestral presence of diacetin might have served as a pre-adaptation for bee pollination, whereas the current mismatch between flower morphology and bees is due to the retention of vestigial floral spurs. These results elucidate the sequence of floral evolution in the early stages of pollinator shifts and help to explain the assembly of suites of co-varying traits through pre-adaptation and vestigialization.9-12.

Dextrose Prolotherapy Versus Lidocaine Injection for Temporomandibular Dysfunction: A Pragmatic Randomized Controlled Trial.

Objective: Several intraarticular injections, including dextrose and lidocaine, are reported to reduce pain and dysfunction in temporomandibular dysfunction (TMD) and increase maximal jaw opening; our goal was to determine whether dextrose/lidocaine outperforms sterile water/lidocaine for TMD. Design: Pragmatic randomized controlled trial. Setting: Outpatient clinic. Subjects: Chronic (≥3 months) of moderate-to-severe (≥6/10) jaw or facial pain meeting research-specific TMD criteria. Intervention: Blinded intraarticular dextrose prolotherapy (DPT) (20% dextrose/0.2% lidocaine) versus intraarticular lidocaine (0.2% lidocaine in sterile water) at 0, 1, and 2 months. Participants were then unblinded and offered DPT by request for 9 additional months. Main outcome measures: Primary: Numerical Rating Scale (0-10 points) score for facial pain and jaw dysfunction; percentage achieving ≥50% improvement in pain and dysfunction (0, 3, and 12 months). Secondary: Maximal interincisal opening (MIO; 0 and 3 months). Intention-to-treat analysis was by joint using mixed-model regression. Results: Randomization of 29 participants (25 female, 47 ± 17 years, 43 joints) produced similar groups. Three-month pain and dysfunction improvements were similar, but more DPT-treated joints improved by ≥50% in pain (17/22 vs. 6/21; p = 0.028). The MIO improved in both groups (5.6 ± 5.8 mm vs. 5.1 ± 7.0 mm; p = 0.70). From 3 to 12 months, minimal DPT was received by original DPT and lidocaine recipients, 0.5 ± 0.9 and 0.6 ± 1.5 injections, respectively, with only 2 out of 21 joints in the original lidocaine group receiving more than 1 dextrose injection after 3 months. Twelve-month analysis revealed that joints in the original DPT group improved more in jaw pain (4.8 ± 2.4 points vs. 2.6 ± 2.9 points; p = 0.026) and jaw dysfunction (5.3 ± 2.6 points vs. 2.7 ± 2.3 points; p = 0.013). More DPT than lidocaine-treated joints improved by ≥50% in both pain (19/22 vs. 5/21; p = 0.003) and dysfunction (17/22 vs. 7/21; p = 0.040). There were no adverse events; satisfaction was high. Conclusions: Intraarticular DPT resulted in clinically important and statistically significant improvement in pain and dysfunction at 12 months compared to lidocaine injection (ClinicalTrials.gov identifier NCT01617356).