Allelic variants of the estrogen receptor genes and frailty phenotype in postmenopausal women.

OBJECTIVE: The prevalence of frailty has been related to menopause. Our main objective was to investigate whether single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER) ERα and ERß genes were related to the frailty phenotype in a population of community-dwelling postmenopausal women. METHODS: A cross-sectional study was performed in which we selected five SNPs, three in the ERα gene and two in the ERß. Linear regression was used to estimate the percentage of phenotypic variance after adjusting for confounding variables. RESULTS: A total of 470 women (mean ± standard deviation age 63.83 ± 8.16 years) were included, of whom 137 women were frail. The SNP rs3798577 of the ERα gene was the only variant associated with frailty, but this significance faded in the multivariant analysis. Body mass index (p = 0.012), number of comorbidities (0 vs. ≥2, p = 0.002) and two reproductive variables, number of miscarriages (none vs. ≥2, p = 0.036) and of childbirths (one vs. ≥3, p = 0.008), were independently related to frailty. CONCLUSION: The five SNPs of the ERα and ERß genes tested were not correlated with frailty. Other SNPs of the ER warrant analysis to clarify whether variance in the gene response affects frailty status.

Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult Mediterranean population.

OBJECTIVES: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. METHODS: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. RESULTS: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. CONCLUSIONS: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.

Bioethical Conflicts in Current Dermatology: A Narrative Review. / Conflictos bioéticos en la dermatología actual: una revisión narrativa.

Both the functions and equipment of dermatologists have increased over the past few years, some examples being cosmetic dermatology, artificial intelligence, tele-dermatology, and social media, which added to the pharmaceutical industry and cosmetic selling has become a source of bioethical conflicts. The objective of this narrative review is to identify the bioethical conflicts of everyday dermatology practice and highlight the proposed solutions. Therefore, we conducted searches across PubMed, Web of Science and Scopus databases. Also, the main Spanish and American deontological codes of physicians and dermatologists have been revised. The authors recommend declaring all conflicts of interest while respecting the patients' autonomy, confidentiality, and privacy. Cosmetic dermatology, cosmetic selling, artificial intelligence, tele-dermatology, and social media are feasible as long as the same standards of conventional dermatology are applied. Nonetheless, the deontological codes associated with these innovations need to be refurbished.

[Translated article] Bioethical Conflicts in Current Dermatology: A Narrative Review.

Both the functions and equipment of dermatologists have increased over the past few years, some examples being cosmetic dermatology, artificial intelligence, tele-dermatology, and social media, which added to the pharmaceutical industry and cosmetic selling has become a source of bioethical conflicts. The objective of this narrative review is to identify the bioethical conflicts of everyday dermatology practice and highlight the proposed solutions. Therefore, we conducted searches across PubMed, Web of Science and Scopus databases. Also, the main Spanish and American deontological codes of physicians and dermatologists have been revised. The authors recommend declaring all conflicts of interest while respecting the patients' autonomy, confidentiality, and privacy. Cosmetic dermatology, cosmetic selling, artificial intelligence, tele-dermatology, and social media are feasible as long as the same standards of conventional dermatology are applied. Nonetheless, the deontological codes associated with these innovations need to be refurbished.

Dentate Gyrus Somatostatin Cells are Required for Contextual Discrimination During Episodic Memory Encoding.

Memory systems ought to store and discriminate representations of similar experiences in order to efficiently guide future decisions. This problem is solved by pattern separation, implemented in the dentate gyrus (DG) by granule cells to support episodic memory formation. Pattern separation is enabled by tonic inhibitory bombardment generated by multiple GABAergic cell populations that strictly maintain low activity levels in granule cells. Somatostatin-expressing cells are one of those interneuron populations, selectively targeting the distal dendrites of granule cells, where cortical multimodal information reaches the DG. Nonetheless, somatostatin cells have very low connection probability and synaptic efficacy with both granule cells and other interneuron types. Hence, the role of somatostatin cells in DG circuitry, particularly in the context of pattern separation, remains uncertain. Here, by using optogenetic stimulation and behavioral tasks in mice, we demonstrate that somatostatin cells are required for the acquisition of both contextual and spatial overlapping memories.

Treatment, outcomes and costs of asthma exacerbations in Chilean children: a prospective multicenter observational study.

OBJECTIVE: To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures. METHODS: Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion. Days with oxygen supply and pharmacological treatments received were recorded from the clinical chart. A basic asthma hospitalization basket was defined in order to estimate the average hospitalization cost for a single patient. Six months after discharge, new visits to the Emergency Room (ER), use of systemic corticosteroids and adherence to the controller treatment were evaluated. RESULTS: 396 patients were enrolled. Patients from the public health system and from the north zone received significantly more days of oxygen, systemic corticosteroids and antibiotics. Great heterogeneity in antibiotic use among the participating hospitals was found, from 0 to 92.3% (ICC 0.34, 95% CI 0.16-0.52). The use of aminophylline, magnesium sulfate and ketamine varied from 0 to 36.4% between the different Pediatric Intensive Care Units (ICC 0.353, 95% CI 0.010-0.608). The average cost per inpatient was of $1910 USD. 290 patients (73.2%) completed the follow-up six months after discharge. 76 patients (26.2%) were not receiving any controller treatment and nearly a fourth had new ER visits and use of systemic corticosteroids due to new asthma exacerbations. CONCLUSIONS: Considerable practice variation in asthma exacerbations treatment was found among the participating hospitals, highlighting the poor outcome of many patients after hospital discharge, with an important health cost.

Hospitalizations for asthma exacerbation in Chilean children: A multicenter observational study.

BACKGROUND: Asthma hospitalization rates in Chilean children have increased in the last 14 years, but little is known about the factors associated with this. OBJECTIVE: Describe clinical characteristics of children hospitalized for asthma exacerbation. METHODS: Observational prospective cohort study in 14 hospitals. Over a one-year period, children five years of age or older hospitalized with asthma exacerbation were eligible for inclusion. Parents completed an online questionnaire with questions on demographic information, about asthma, indoor environmental contaminant exposure, comorbidities and beliefs about disease and treatment. Disease control was assessed by the Asthma Control Test. Inhalation technique was observed using a checklist. RESULTS: 396 patients were enrolled. 168 children did not have an established diagnosis of asthma. Only 188 used at least one controller treatment at the time of hospitalization. 208 parents said they believed their child had asthma only when they had an exacerbation and 97 correctly identified inhaled corticosteroids as anti-inflammatory treatment. 342 patients used the wrong spacer and 73 correctly performed all steps of the checklist. CONCLUSIONS: Almost half of the patients were not diagnosed with asthma at the time of hospitalization despite having a medical history suggestive of the disease. In the remaining patients with an established diagnosis of asthma potentially modifiable factors like bad adherence to treatment and poor inhalation technique were found. Implementing a nationwide asthma program including continued medical education for the correct diagnosis and follow up of these patients and asthma education for patients and caregivers is needed to reduce asthma hospitalization rates in Chilean children.

A translational approach from an animal model identifies CD80 as a candidate gene for the study of bone phenotypes in postmenopausal women.

This study represented a translational study that first compared gene expression of B cells of BM from ovariectomized and control mice, and then analyzed some of the differentially expressed genes in women. Results showed novel genetic associations with bone phenotypes and points to the CD80 gene as relevant in postmenopausal bone loss. INTRODUCTION: Osteoporosis is a multifactorial disease with a strong genetic component. However, to date, research into osteoporosis has only been able to explain a small part of its heritability. Moreover, several components of the immune system are involved in the regulation of bone metabolism. Among them, B cells occupy a prominent place. METHODS: The study consisted of two stages. In the first, gene expression in bone marrow B cells is compared between ovariectomized and SHAM control mice using microarrays. In the second, we studied the association of polymorphisms in some differentially expressed genes (DEG) in a cohort of postmenopausal women. RESULTS: The present study has found 2791 DEG (false discovery rate (FDR) <5%), of which 1569 genes were upregulated (56.2%) and 1122 genes (43.8%) were downregulated. Among the most altered pathways were inflammation, interleukin signaling, B cell activation, TGF-beta signaling, oxidative stress response, and Wnt-signaling. Sixteen DEG were validated by MALDI-TOF mass spectrometry or qPCR. The translational stage of the study genotyped nine single nucleotide polymorphisms (SNPs) of DEG or related and detected association with bone mineral density (BMD) (nominal P values), while adjusting for confounders, for SNPs in the CD80, CD86, and HDAC5 genes. In the logistic regression analysis adjusted for confounders, in addition to the SNPs in the aforementioned genes, the SNPs in the MMP9 and SOX4 genes were associated with an increased risk of osteoporosis. Finally, two SNPs (in the CD80 and SOX6 genes) were associated with an increased risk of bone fragility fracture (FF). However, after Bonferroni correction for multiple testing, only the association between CD80 with BMD and risk of osteoporosis remained significant. CONCLUSION: These results show that the use of animal models is an appropriate method for identifying genes associated with human bone phenotypes.

Hoxa-10 and Cyclin D3 Overexpression in the Decidual Reaction in a Superovulation Protocol in Young Adult C57BL/6J Mice.

Following the performance of a superovulation protocol, multiple nodules were observed bilaterally in the uterine horns of 31 of 276 (11.2%) C57BL/6 J female mice aged 8.5 ± 0.6 (mean and standard error of mean) weeks. These lesions prevented embryo collection, and the uterine decidual reaction was suspected. Samples of pathological uteri (n = 20) and the normal genital tracts of donors treated with a similar superovulation protocol (control group, n = 10) were collected. Immunohistochemistry was performed to evaluate pancytokeratin, desmin, vimentin, progesterone receptor (PR), estrogen receptor α (ERα), Ki-67, cyclin D3 and c-Myc expression, as well as quantitative polymerase chain reaction to assess cyclin D3, Hoxa-10 and heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA expression. The uterine decidual reaction presented a high degree of structural organization and specifically affected the antimesometrial region of the endometrium. The abnormal decidual cells were large polygonal cells that were frequently polyploid or binucleated and strongly positive for desmin. Immunohistochemistry showed higher Ki-67 proliferation index and higher expression of PR and cyclin D3 in decidual cells in the antimesometrial aspect of the endometrium, compared to nondecidualized endometrial stromal cells in the mesometrial aspect of affected uteri, and compared to endometrial stromal cells in healthy uteri. High expression of cyclin D3 and Hoxa-10 mRNA was also observed in uteri affected by the decidual reaction. These results suggest that PR overexpression in endometrial stromal cells, likely due to high progesterone levels, triggers cyclin D3 and Hoxa-10 overexpression, which may be involved in the pathological mechanisms of the mouse uterine decidual reaction.

Discrepancies between clinical assessments of sensory function and electrical perceptual thresholds after incomplete chronic cervical spinal cord injury.

STUDY DESIGN: Prospective experimental. OBJECTIVES: To compare sensory function as revealed by light touch and pin prick tests of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and the electrical perceptual threshold (EPT) exams in individuals with chronic incomplete cervical spinal cord injury (SCI). SETTING: Pittsburgh, United States. METHODS: EPT was tested using cutaneous electrical stimulation (0.5 ms pulse width, 3 Hz) in 32 healthy controls and in 17 participants with SCI over key points on dermatomes C2 to T4 on each side of the body. Light touch and pin prick ISNCSCI scores were tested at the same key dermatomes in SCI participants. RESULTS: In controls, EPT values were higher in older males (1.26±0.2 mA, mean±s.d.) compared with younger males (1.0±0.2 mA) and older females (0.9±0.2 mA), regardless of the dermatome and side tested. Fifteen out of the seventeen SCI participants showed that the level of sensory impairment detected by the EPT was below the level detected by the ISNCSCI (mean=4.5±2.4, range 1-9). The frequency distribution of EPTs was similar to older male controls in dermatomes above but not below the ISNCSCI sensory level. The difference between EPT and ISNCSCI sensory level was negatively correlated with the time post injury. CONCLUSIONS: The results show that, in the chronic stage of cervical SCI, the EPT reveals spared sensory function at lower (~5) spinal segments compared with the ISNCSCI sensory exam. It is hence found that the EPT is a sensitive tool to assess recovery of sensory function after chronic SCI.

[Analysis of an incident notification system and register in a critical care unit]. / Análisis del registro de un sistema de notificación de incidentes en una unidad de cuidados críticos.

OBJECTIVE: To analyse the incident communicated through a notification system and register in a critical care unit. METHODOLOGY: A cross-sectional descriptive study was conducted by performing an analysis of the records of incidents communicated anonymously and voluntarily from January 2007 to December 2013 in a critical care unit of adult patients with severe trauma. STUDY VARIABLES: incident type and class, professional reports, and suggestions for improvement measures. A descriptive analysis was performed on the variables. RESULTS: Out of a total of 275 incidents reported, 58.5% of them were adverse events. Incident distributed by classes: medication, 33.7%; vascular access-drainage-catheter-sensor, 19.6%; devices-equipment, 13.3%, procedures, 11.5%; airway tract and mechanical ventilation, 10%; nursing care, 4.1%; inter-professional communication, 3%; diagnostic test, 3%; patient identification, 1.1%, and transfusion 0.7%. In the medication group, administrative errors accounted for a total of 62%; in vascular access-drainage-catheter-sensor group, central venous lines, a total of 27%; in devices and equipment group, respirators, a total of 46.9%; in airway self-extubations, a total of 32.1%. As regards to medication errors, 62% were incidents without damage. Incident notification by profession: doctors, 43%, residents, 5.6%, nurses, 51%, and technical assistants, 0.4%. CONCLUSIONS: Adverse events are the most communicated incidents. The events related to medication administration are the most frequent, although most of them were without damage. Nurses and doctors communicate the incidents with the same frequency. In order to highlight the low incident notification despite it being an anonymous and volunteer system, therefore, it is suggested to study measurements to increase the level of communication.

Gold-palladium core@shell nanoalloys: experiments and simulations.

In this work, we report a facile synthesis route, structural characterization, and full atomistic simulations of gold-palladium nanoalloys. Through aberration corrected-STEM, UV-vis spectroscopy and EDS chemical analysis, we were able to determine that Au(core)-Pd(shell) bimetallic nanoparticles were formed. Using different computational approaches, we were capable of establishing how the size of the core and the thickness of the shell will affect the thermodynamic stability of several core-shell nanoalloys. Finally, grand canonical simulations using different sampling procedures were used to study the growth mechanism of Pd atoms on Au seeds of different shapes.

Effects on growth and osteogenic differentiation of mesenchymal stem cells by the strontium-added sol-gel hydroxyapatite gel materials.

In the present study, strontium-modified hydroxyapatite gels (Sr-HA) at different concentrations were prepared using sol-gel approach and their effect on human-bone-marrow-derived mesenchymal stem cells, were evaluated. The effect of Strontium on physico-chemical and morphological properties of hydroxyapatite gel were evaluated. Morphological analyses (SEM and TEM) demonstrate that an increasing in the amount of Sr ions doped into HA made the agglomerated particles smaller. The substitution of large Sr2+ for small Ca2+ lead to denser atomic packing of the system causing retardation of crystals growth. The biological results demonstrated that hydroxyapatite gel containing from 0 to 20 mol% of Sr presented no cytotoxicity and promote the expression of osteogenesis related genes including an early marker for osteogenic differentiation ALP; a non-collagen protein OPN and a late marker for osteogenic differentiation OCN. Finally, the Sr-HA gels could have a great potential application as filler in bone repair and regeneration and used in especially in the osteoporotic disease.

Patterns of pollen dispersal in a small population of the Canarian endemic palm (Phoenix canariensis).

The genetic diversity of small populations is greatly influenced by local dispersal patterns and genetic connectivity among populations, with pollen dispersal being the major component of gene flow in many plants species. Patterns of pollen dispersal, mating system parameters and spatial genetic structure were investigated in a small isolated population of the emblematic palm Phoenix canariensis in Gran Canaria island (Canary Islands). All adult palms present in the study population (n=182), as well as 616 seeds collected from 22 female palms, were mapped and genotyped at 8 microsatellite loci. Mating system analysis revealed an average of 5.8 effective pollen donors (Nep) per female. There was strong variation in correlated paternity rates across maternal progenies (ranging from null to 0.9) that could not be explained by the location and density of local males around focal females. Paternity analysis revealed a mean effective pollen dispersal distance of ∼71 m, with ∼70% of effective pollen originating from a distance of <75 m, and 90% from <200 m. A spatially explicit mating model indicated a leptokurtic pollen dispersal kernel, significant pollen immigration (12%) from external palm groves and a directional pollen dispersal pattern that seems consistent with local altitudinal air movement. No evidence of inbreeding or genetic diversity erosion was found, but spatial genetic structure was detected in the small palm population. Overall, the results suggest substantial pollen dispersal over the studied population, genetic connectivity among different palm groves and some resilience to neutral genetic erosion and subsequently to fragmentation.

Bioactivation of calcium deficient hydroxyapatite with foamed gelatin gel. A new injectable self-setting bone analogue.

An alternative approach to bone repair for less invasive surgical techniques, involves the development of biomaterials directly injectable into the injury sites and able to replicate a spatially organized platform with features of bone tissue. Here, the preparation and characterization of an innovative injectable bone analogue made of calcium deficient hydroxyapatite and foamed gelatin is presented. The biopolymer features and the cement self-setting reaction were investigated by rheological analysis. The porous architecture, the evolution of surface morphology and the grains dimension were analyzed with electron microscopy (SEM/ESEM/TEM). The physico-chemical properties were characterized by X-ray diffraction and FTIR analysis. Moreover, an injection test was carried out to prove the positive effect of gelatin on the flow ensuing that cement is fully injectable. The cement mechanical properties are adequate to function as temporary substrate for bone tissue regeneration. Furthermore, MG63 cells and bone marrow-derived human mesenchymal stem cells (hMSCs) were able to migrate and proliferate inside the pores, and hMSCs differentiated to the osteoblastic phenotype. The results are paving the way for an injectable bone substitute with properties that mimic natural bone tissue allowing the successful use as bone filler for craniofacial and orthopedic reconstructions in regenerative medicine.