Variability in performance of genetic-enhanced DXA-BMD prediction models across diverse ethnic and geographic populations: A risk prediction study.

BACKGROUND: Osteoporosis is a major global health issue, weakening bones and increasing fracture risk. Dual-energy X-ray absorptiometry (DXA) is the standard for measuring bone mineral density (BMD) and diagnosing osteoporosis, but its costliness and complexity impede widespread screening adoption. Predictive modeling using genetic and clinical data offers a cost-effective alternative for assessing osteoporosis and fracture risk. This study aims to develop BMD prediction models using data from the UK Biobank (UKBB) and test their performance across different ethnic and geographical populations. METHODS AND FINDINGS: We developed BMD prediction models for the femoral neck (FNK) and lumbar spine (SPN) using both genetic variants and clinical factors (such as sex, age, height, and weight), within 17,964 British white individuals from UKBB. Models based on regression with least absolute shrinkage and selection operator (LASSO), selected based on the coefficient of determination (R2) from a model selection subset of 5,973 individuals from British white population. These models were tested on 5 UKBB test sets and 12 independent cohorts of diverse ancestries, totaling over 15,000 individuals. Furthermore, we assessed the correlation of predicted BMDs with fragility fractures risk in 10 years in a case-control set of 287,183 European white participants without DXA-BMDs in the UKBB. With single-nucleotide polymorphism (SNP) inclusion thresholds at 5×10-6 and 5×10-7, the prediction models for FNK-BMD and SPN-BMD achieved the highest R2 of 27.70% with a 95% confidence interval (CI) of [27.56%, 27.84%] and 48.28% (95% CI [48.23%, 48.34%]), respectively. Adding genetic factors improved predictions slightly, explaining an additional 2.3% variation for FNK-BMD and 3% for SPN-BMD over clinical factors alone. Survival analysis revealed that the predicted FNK-BMD and SPN-BMD were significantly associated with fragility fracture risk in the European white population (P < 0.001). The hazard ratios (HRs) of the predicted FNK-BMD and SPN-BMD were 0.83 (95% CI [0.79, 0.88], corresponding to a 1.44% difference in 10-year absolute risk) and 0.72 (95% CI [0.68, 0.76], corresponding to a 1.64% difference in 10-year absolute risk), respectively, indicating that for every increase of one standard deviation in BMD, the fracture risk will decrease by 17% and 28%, respectively. However, the model's performance declined in other ethnic groups and independent cohorts. The limitations of this study include differences in clinical factors distribution and the use of only SNPs as genetic factors. CONCLUSIONS: In this study, we observed that combining genetic and clinical factors improves BMD prediction compared to clinical factors alone. Adjusting inclusion thresholds for genetic variants (e.g., 5×10-6 or 5×10-7) rather than solely considering genome-wide association study (GWAS)-significant variants can enhance the model's explanatory power. The study highlights the need for training models on diverse populations to improve predictive performance across various ethnic and geographical groups.

Measurement of Protein Kinetics Using a Liquid Phase-Based Biosensing Platform.

Macromolecular association is crucial to many fields in biomedical sciences, including drug development, gene editing, and diagnostics. In particular, protein-protein association and dissociation rate constants are typically determined using surface plasmon resonance systems, which require costly instrumentation and cumbersome procedures (e.g., blocking, washing, and separation). Herein, we demonstrate that protein-binding constants can be readily determined using a real-time biosensing platform facilitated by graphene oxide-modified microwell plates and fluorophore-labeled proteins, where the fluorescent probes remain highly fluorescent during protein association, whereas fluorescent bioprobes that are not associated with their counterparts are quenched by graphene oxide. Binding data of three pairs of proteins were systematically determined employing this single-step platform and compared with those data reported by the suppliers or the literature, suggesting that this approach is comparable and consistent with the existing ones. Such pairs include (i) human immunoglobulin G (H-IgG)-fluorophore-labeled anti-H-IgG, (ii) prostate-specific antigen (PSA)-quantum dot-labeled anti-PSA, and (iii) anti-RBD-fluorophore-labeled SARS-CoV-2 spike receptor-binding domain recombinant protein. We also offer an open-source software that automatically determines the binding kinetics constants of proteins. This Technical Note introduces a simple, yet effective, platform to determine relevant information on protein kinetics, which can be performed using a microwell plate reader and economical materials like graphene oxide. We foresee a new generation of diagnostics based on our affordable protein kinetics analysis.

Barriers to Quality Perioperative Care Delivery in Low- and Middle-Income Countries: A Qualitative Rapid Appraisal Study.

BACKGROUND: Provision of timely, safe, and affordable surgical care is an essential component of any high-quality health system. Increasingly, it is recognized that poor quality of care in the perioperative period (before, during, and after surgery) may contribute to significant excess mortality and morbidity. Therefore, improving access to surgical procedures alone will not address the disparities in surgical outcomes globally until the quality of perioperative care is addressed. We aimed to identify key barriers to quality perioperative care delivery for 3 "Bellwether" procedures (cesarean delivery, emergency laparotomy, and long-bone fracture fixation) in 5 low- and middle-income countries (LMICs). METHODS: Ten hospitals representing secondary and tertiary facilities from 5 LMICs were purposefully selected: 2 upper-middle income (Colombia and South Africa); 2 lower-middle income (Sri Lanka and Tanzania); and 1 lower income (Uganda). We used a rapid appraisal design (pathway mapping, ethnography, and interviews) to map out and explore the complexities of the perioperative pathway and care delivery for the Bellwether procedures. The framework approach was used for data analysis, with triangulation across different data sources to identify barriers in the country and pattern matching to identify common barriers across the 5 LMICs. RESULTS: We developed 25 pathway maps, undertook >30 periods of observation, and held >40 interviews with patients and clinical staff. Although the extent and impact of the barriers varied across the LMIC settings, 4 key common barriers to safe and effective perioperative care were identified: (1) the fragmented nature of the care pathways, (2) the limited human and structural resources available for the provision of care, (3) the direct and indirect costs of care for patients (even in health systems for which care is ostensibly free of charge), and (4) patients' low expectations of care. CONCLUSIONS: We identified key barriers to effective perioperative care in LMICs. Addressing these barriers is important if LMIC health systems are to provide safe, timely, and affordable provision of the Bellwether procedures.

An exploration of the variability of physiological responses to soil drying in relation with C/N balance across three species of the under-utilized genus Vigna.

The genus Vigna (Fabaceae) is an agriculturally important taxon, which includes several crop species such as cowpea (Vigna unguiculata L.), mung bean (Vigna radiata) and azuki bean (Vigna angularis). Most studies have focused on cowpea (V. unguiculata (L.) as a drought-resistant crop, although insights on the mechanisms that confer this species the ability to grow in dry environment are still not fully resolved. The diversity of this rich genus has been overlooked in many physiological studies. This study explores the physiological mechanisms of response to soil drying (N2 fixation, transpiration rate and changes in C and N allocation) across three species of the Vigna genus: V. radiata, V. unguiculata, V. vexillata (tuber cowpea). A significant variability among the studied Vigna accessions was found for the threshold in decline of N2 fixation with soil drying. Less variability was observed in the transpiration threshold. Through the analysis of leaf traits variation under well-watered and water-deficit conditions, we were able to relate the variability in N2 fixation and transpiration response to C/N metabolism modifications resulting in different allocation of carbon and nitrogen to leaves under water deficit.

Historical Perspectives on the Removal of Intraradicular Posts Prior to the Availability of Ultrasonic Applications.

For decades the dismantling of previous dental work to correct inferior root canal procedures or to address recurrent dental caries has provided a significant amount of work for the restorative dentist. When coupled with teeth that have been root treated and also have an intraradicular post or dowel, the clinician was often presented with the challenge of post removal, without fracturing the root, and revision (retreatment) of the root canal procedures. While today's contemporary dentistry has the wherewithal to use ultrasonic devices to loosen and remove the post, this was not always the case historically, and creativity in this process was the hallmark of many of our predecessors.

Deregulated MicroRNAs in Cancer-Associated Fibroblasts from Front Tumor Tissues of Lung Adenocarcinoma as Potential Predictors of Tumor Promotion.

Cancer-associated fibroblasts (CAFs) are the main component of the tumor stroma and promote tumor progression through several mechanisms. Recent evidence indicates that small noncoding RNAs, microRNAs (miRNAs), play key roles in CAF tumor-promoting properties; however, the role of miRNAs in lung cancer-associated fibroblasts remains poorly defined. We characterized the differential miRNA expression profile of fibroblasts isolated from matched tumor front (F-CAFs), inner tumor (In-CAFs), and normal adjacent (NFs) tissues from four lung adenocarcinoma patients (ADs) using microarray analysis. Proliferation and invasion assays of A549 human lung cancer cells in the presence of conditioned medium from F-CAFs, In-CAFs or NFs were performed to assess tumorigenic properties. Ten identified candidate miRNAs in F-CAFs, In-CAFs and NFs from 12 ADs were then validated by RT-PCR. Both F-CAFs and In-CAFs enhanced the proliferation and invasion of A549 cells compared with NFs; moreover, F-CAFs showed a significantly stronger effect than In-CAFs. RT-PCR validation demonstrated three downregulated miRNAs in F-CAFs compared with NFs (miR-145-3p, miR-299-3p, and miR-505-3p), two in F-CAFs compared with In-CAFs (miR-410-3p and miR-485-5p), but no differentially expressed miRNAs between In-CAFs and NFs. Further target-gene prediction and pathway enrichment analysis indicated that deregulated miRNAs in F-CAFs showed significant associations with "pathways in cancer" (miR-145-3p, miR-299-3p and miR-410-3p), "Wnt signaling pathway" (miR-410-3p and miR-505-3p), and "TGF-beta signaling pathway" (miR-410-3p). Importantly, a tumor-promoting growth factor targeted by those miRNAs, VEGFA, was upregulated in F-CAFs compared with NFs, as judged by RT-PCR. In conclusion, deregulated miRNAs in F-CAFs are potentially associated with CAF tumor-promoting properties.

Characteristic plethysmographic findings in a guinea pig model of COPD.

AIM OF THE STUDY: Long-term exposure to cigarette smoke generates chronic obstructive pulmonary disease (COPD) in guinea pigs, but a comprehensive evaluation of changes in lung function, as assessed by barometric whole body plethysmography (WBP), is lacking. MATERIALS AND METHODS: Female guinea pigs were exposed to the smoke of 20 cigarettes/day, 5 days/week, during 10 weeks (COPD group, n = 8), and were compared with unexposed female guinea pigs of the same age (control group, n = 8). WBP was performed in both groups, followed by lung histology. RESULTS: At the end of the exposure period, guinea pigs in the COPD group had higher respiratory frequency, while duty cycle (Ti/Ttot) was unaffected. There was a trend toward minute ventilation (MV) and expiratory flow at the mid-tidal volume (EF50) to be higher in the COPD group. Enhanced pause (Penh) was lower, while time of braking (TB) and time to PEF relative to Te (Rpef) were higher in the COPD group. All guinea pigs exposed to tobacco smoke developed emphysematous lesions in their lungs and gained less body weight than controls. CONCLUSIONS: In this COPD model, exposure to cigarette smoke produced changes in WBP characterized by a shallow breathing pattern with decreased Penh and a trend toward increasing EF50 (probably due to decreased elastic recoil), increased TB (suggesting dynamic laryngeal narrowing), and a trend of increasing MV (probably due to a higher metabolic rate). Many of these functional changes resemble those observed in patients with COPD and corroborate the suitability of this guinea pig model for the study of COPD.

Identification and characterization of large DNA deletions affecting oil quality traits in soybean seeds through transcriptome sequencing analysis.

KEY MESSAGE: Identification and characterization of a 254-kb genomic deletion on a duplicated chromosome segment that resulted in a low level of palmitic acid in soybean seeds using transcriptome sequencing. A large number of soybean genotypes varying in seed oil composition and content have been identified. Understanding the molecular mechanisms underlying these variations is important for breeders to effectively utilize them as a genetic resource. Through design and application of a bioinformatics approach, we identified nine co-regulated gene clusters by comparing seed transcriptomes of nine soybean genotypes varying in oil composition and content. We demonstrated that four gene clusters in the genotypes M23, Jack and N0304-303-3 coincided with large-scale genome rearrangements. The co-regulated gene clusters in M23 and Jack mapped to a previously described 164-kb deletion and a copy number amplification of the Rhg1 locus, respectively. The coordinately down-regulated gene clusters in N0304-303-3 were caused by a 254-kb deletion containing 19 genes including a fatty acyl-ACP thioesterase B gene (FATB1a). This deletion was associated with reduced palmitic acid content in seeds and was the molecular cause of a previously reported nonfunctional FATB1a allele, fap nc . The M23 and N0304-304-3 deletions were located in duplicated genome segments retained from the Glycine-specific whole genome duplication that occurred 13 million years ago. The homoeologous genes in these duplicated regions shared a strong similarity in both their encoded protein sequences and transcript accumulation levels, suggesting that they may have conserved and important functions in seeds. The functional conservation of homoeologous genes may result in genetic redundancy and gene dosage effects for their associated seed traits, explaining why the large deletion did not cause lethal effects or completely eliminate palmitic acid in N0304-303-3.

Dopamine-dependent modulation of rat globus pallidus excitation by nicotine acetylcholine receptors.

The globus pallidus (GP) coordinates information processing in the basal ganglia nuclei. The contribution of nicotinic cholinergic receptors (nAChRs) to the spiking activity of GP neurons is largely unknown. Several studies have reported that the effect of nAChRs in other nuclei depends on dopaminergic input. Via in vivo single unit extracellular recordings and intranuclear drug infusions, we analyzed the effects of local activation and blockade of nAChRs in neurons of both sham and 6-hydroxydopamine (6-OHDA)-lesioned rats. In sham rats, the local application of nicotine and edrophonium (an acetylcholinesterase inhibitor) increases GP neurons spiking rate. Local application of mecamylamine, a neuronal nicotinic cholinergic antagonist, diminishes pallidal neurons spiking rate, an effect not produced by d-tubocurarine, a peripheral nicotinic cholinergic antagonist. Moreover, mecamylamine blocks the excitatory effect evoked by nicotine and edrophonium. In 6-OHDA-lesioned rats, local infusion of nicotine does not change pallidal neurons firing rate. Our results show that there is a tonic cholinergic input to the GP that increases their spiking rate through the activation of nAChRs and that this effect depends on functional dopaminergic pathways.

Mapping the low palmitate fap1 mutation and validation of its effects in soybean oil and agronomic traits in three soybean populations.

KEY MESSAGE: fap 1 mutation is caused by a G174A change in GmKASIIIA that disrupts a donor splice site recognition and creates a GATCTG motif that enhanced its expression. Soybean oil with reduced palmitic acid content is desirable to reduce the health risks associated with consumption of this fatty acid. The objectives of this study were: to identify the genomic location of the reduced palmitate fap1 mutation, determine its molecular basis, estimate the amount of phenotypic variation in fatty acid composition explained by this locus, determine if there are epistatic interactions between the fap1 and fap nc loci and, determine if the fap1 mutation has pleiotropic effects on seed yield, oil and protein content in three soybean populations. This study detected two major QTL for 16:0 content located in chromosome 5 (GmFATB1a, fap nc) and chromosome 9 near BARCSOYSSR_09_1707 that explained, with their interaction, 66-94 % of the variation in 16:0 content in the three populations. Sequencing results of a putative candidate gene, GmKASIIIA, revealed a single unique polymorphism in the germplasm line C1726, which was predicted to disrupt the donor splice site recognition between exon one and intron one and produce a truncated KASIIIA protein. This G to A change also created the GATCTG motif that enhanced gene expression of the mutated GmKASIIIA gene. Lines homozygous for the GmKASIIIA mutation (fap1) had a significant reduction in 16:0, 18:0, and oil content; and an increase in unsaturated fatty acids content. There were significant epistatic interactions between GmKASIIIA (fap1) and fap nc for 16:0 and oil contents, and seed yield in two populations. In conclusion, the fap1 phenotype is caused by a single unique SNP in the GmKASIIIA gene.

Detection of residual organochlorine and organophosphorus pesticides in agricultural soil in Rio Verde region of San Luis Potosi, Mexico.

Organochlorine pesticides were intensively used in Mexico from 1950 until their ban and restriction in 1991. However, the presence of these compounds is commonly reported in many regions of the country. The aim of the present study was to identify and quantify residual organochlorine and organophosphorus pesticides in agricultural soil in Rio Verde region, San Luis Potosi state, which has been identified as possibly polluted by pesticides. Composed samples from 24 zones covering an area of approximately 5,440 ha were analyzed. The most frequently found pesticides were p,p'-DDT followed by ,p,p'-DDE, heptachlor, endosulfan and γ-HCH whose frequency rates were 100, 91, 83 and 54%, respectively. The concentration of p,p'-DDT in the crops grown in these soils was in the following order: chili > maize > tomato > alfalfa. The results obtained in this study show that p,p'-DDT values are lower or similar to those found in other agricultural regions of Mexico. Methyl and ethyl parathion were the most frequent organophosphate pesticide detected in 100% and 62.5% of the samples with average concentrations of 25.20 and 47.48 µg kg(-1), respectively. More research is needed to establish the background levels of pesticides in agricultural soils and their potential ecological and human health effects in this region.

Assessing the fragility index of randomized controlled trials supporting perioperative care guidelines: A methodological survey protocol.

INTRODUCTION: The Fragility Index (FI) and the FI family are statistical tools that measure the robustness of randomized controlled trials (RCT) by examining how many patients would need a different outcome to change the statistical significance of the main results of a trial. These tools have recently gained popularity in assessing the robustness or fragility of clinical trials in many clinical areas and analyzing the strength of the trial outcomes underpinning guideline recommendations. However, it has not been applied to perioperative care Clinical Practice Guidelines (CPG). OBJECTIVES: This study aims to survey clinical practice guidelines in anesthesiology to determine the Fragility Index of RCTs supporting the recommendations, and to explore trial characteristics associated with fragility. METHODS AND ANALYSIS: A methodological survey will be conducted using the targeted population of RCT referenced in the recommendations of the CPG of the North American and European societies from 2012 to 2022. FI will be assessed for statistically significant and non-significant trial results. A Poisson regression analysis will be used to explore factors associated with fragility. DISCUSSION: This methodological survey aims to estimate the Fragility Index of RCTs supporting perioperative care guidelines published by North American and European societies of anesthesiology between 2012 and 2022. The results of this study will inform the methodological quality of RCTs included in perioperative care guidelines and identify areas for improvement.

Serology survey of Ascaris suum and Trichinella spiralis in rural pigs in Southwestern Mexico.

BACKGROUND: Parasitic diseases of pigs are a public and veterinary health problem. Helminths influence pork production, whereas backyard pigs can transmit these parasites. OBJECTIVES: This work aimed to investigate the prevalence of antibodies against Ascaris suum and Trichinella spiralis in backyard pigs from Jamiltepec, Region de la Costa, Oaxaca, in Southwestern Mexico. METHODS: Six hundred sixty-four serum samples were obtained from backyard pigs from 23 rural villages distributed in 5 municipalities; samples were taken in a non-probabilistic manner with the owner's consent. The presence of serum antibodies against a total extract of A. suum adult worm was determined by ELISA. In contrast, antibodies to the excretion-secretion products of the T. spiralis muscle larva were determined by Western blot. RESULTS: The global seroprevalence for A. suum was 5.12% and 2.41% for T. spiralis; however, antibodies were only found in 8 villages and distributed in 3 municipalities. The highest frequency of positivity for Ascaris was found in the municipality of Santa Catarina Mechoacán (13.01%), whereas, in Santa María Huazalotitlán, the highest frequency of positivity for Trichinella was found (5.75%). In San Andrés, frequencies were 7.23% and 4.82%, respectively. No statistical differences were observed between populations. CONCLUSIONS: Our data suggest that helminth transmission is restricted by locality. However, further studies must be conducted to understand the factors limiting this transmission to promote pork meat production in parasite-free zones.

The effect of bariatric surgery on metabolic syndrome: A retrospective cohort study in Colombia.

Introduction and Objective: Metabolic syndrome (MetS) represents a group of metabolic abnormalities. It is currently a pandemic, and its prevalence is on the rise. MetS has a direct relationship with obesity, for this reason, bariatric and metabolic surgery has been proposed as a method to simultaneously control obesity and MetS. However, in Colombia the results of this intervention are unknown. This study aims to compare metabolic syndrome before and after bariatric surgery in a Colombian population. Methods: Retrospective cohort study conducted in a highly complex institution in Colombia, where comparing the prevalence of metabolic syndrome in patients who underwent bariatric surgery during a 1-year follow-up period, between January 2015 and December 2019. Of these patients, 48 underwent Roux-en-Y gastric bypass, and 32 underwent sleeve gastrectomy by laparoscopic technique. Results: A total of 80 patients were included, of which 67.5% were women and the mean age was 42.8 ± 12.9 years. The most frequent preprocedure comorbidities were arterial hypertension (36.2%), dyslipidemia (32.4%), and sleep apnea (20%). After bariatric surgery, the prevalence of metabolic syndrome decreased from 66.2% to 3.7% (p < 0.05). In addition, a reduction in the Homeostatic Model Assessment for Insulin Resistance score from 77.5% to 22.5% was observed during the follow-up period. HbA1c, creatinine, and thyroid-stimulating hormone, were the only parameters without significant changes. Conclusions: Metabolic and bariatric surgery is an effective treatment for weight reduction, with a high impact in reducing the prevalence of metabolic syndrome and insulin resistance in the short and medium term in the Colombian population.

miRNAs signature as potential biomarkers for cervical precancerous lesions in human papillomavirus positive women.

Biomarkers to identify women at risk of cervical cancer among those with high-risk HPV infection (hrHPV+) are needed. Deregulated expression of microRNAs (miRNAs) contributes to hrHPV-induced cervical carcinogenesis. We aimed at identifying miRNAs with the capacity to distinguish high (CIN2+) and low (≤ CIN1) grade cervical lesions. We sequenced miRNA libraries from Formalin-Fixed Paraffin-Embedded (FFPE) tissues from women with CIN2+ (n = 10) and age-matched women with ≤ CIN1 (n = 10), randomly and retrospectively selected from a trial that followed women for 24 months after a hrHPV+ test at the screening visit. Five miRNAs differentially expressed were validated by RT-qPCR in an independent set of FFPE tissues with a reviewed diagnosis of CIN2+ (n = 105) and ≤ CIN1 (n = 105). The Ingenuity Pathway Analysis (IPA) was conducted to identify mRNAs inversely correlated with the top 25 differentially expressed miRNAs. Inverse correlations with 401 unique mRNA targets were identified for fourteen of the top 25 differentially expressed miRNAs. Eleven of these miRNAs targeted 26 proteins of pathways deregulated by HPV E6 and E7 oncoproteins and two of them, miR-143-5p and miR-29a-3p, predicted CIN2+ and CIN3+ in the independent validation by RT-qPCR of FFPE tissues from hrHPV-positive women.

[Interdisciplinary management of obesity and overweight in cardiac rehabilitation: review of the Mexican Society for Heart Care (Sociedad Mexicana para el Cuidado del Corazón, SOMECCOR)]. / Manejo interdisciplinario de la obesidad y el sobrepeso en rehabilitación cardiaca: revisión de la Sociedad Mexicana para el Cuidado del Corazón.

Background: Obesity is a multifactorial disorder characterized by increased body adiposity with a wide prevalence in our country, at any age, and linked to major adverse consequences, including the development of heart disease. Cardiac rehabilitation (CR) programs are interdisciplinary interventions aimed not only at restoring the lost functionality of patients who have suffered a cardiovascular outcome, but also at correcting those risk factors that led to it and that interfere with its adaptive results. Obesity contributes to perpetuating heart disease risk and is often resistant to conventional lifestyle modifications. Objective: Establish guidelines in the recognition of obesity with care guidelines for patients with heart disease within CR programs and their interdisciplinary approach. Method: Through an extensive bibliographical review and after an interdisciplinary discussion, this document was prepared to establish a position on the approach to obesity in the context of CR programs in patients with heart disease. Results and conclusions: Our Society recognizes the interdisciplinary approach of our patients with obesity and heart disease in its primary and secondary prevention, urges precision in its diagnosis and assessment, recommends that its primary axis must be based in the first instance on lifestyle modifications (physical training, nutritional care and psycho-emotional intervention), while pharmacological therapy and bariatric surgery could be coadjuvants in optimizing the results in selected patients.

Antecedentes: La obesidad es un trastorno multifactorial caracterizado por un aumento en la adiposidad corporal, de amplia prevalencia en nuestro país, a cualquier edad y ligada a grandes consecuencias adversas, incluyendo el desarrollo de cardiopatías. Los programas de rehabilitación cardiaca (RC) son intervenciones interdisciplinarias encaminadas no solo a restaurar la funcionalidad perdida de los pacientes que han sufrido un desenlace cardiovascular, sino también a corregir aquellos factores de riesgo que lo propiciaron y que interfieren en los resultados adaptativos del mismo. La obesidad contribuye a perpetuar el riesgo de cardiopatía y suele ser resistente a las modificaciones del estilo de vida de manera convencional. Objetivo: Establecer pautas en el reconocimiento de la obesidad con directrices de atención al paciente con cardiopatía dentro de los programas de RC y su abordaje interdisciplinario. Método: A través de una extensiva revisión bibliográfica y después de una discusión interdisciplinaria, se elaboró el presente documento para fijar una postura sobre el abordaje de la obesidad en el contexto de los programas de RC en pacientes con cardiopatía. Resultados y conclusiones: Nuestra Sociedad reconoce el abordaje interdisciplinario de los pacientes con obesidad y cardiopatía en su prevención primaria y secundaria, insta a la precisión en su diagnóstico y valoración, y recomienda que su eje primario debe estar basado en primera instancia en las modificaciones del estilo de vida (entrenamiento físico, atención nutricional e intervención psicoemocional), en tanto que la terapia farmacológica y la cirugía bariátrica pudieran ser coadyuvantes en la optimización de los resultados en pacientes selectos.

The PTPN22 C1858T variant as a risk factor for rheumatoid arthritis and systemic lupus erythematosus but not for systemic sclerosis in the Colombian population.

OBJECTIVES: C1858T single nucleotide polymorphism in PTPN22 encoding the R620W allele variant of Lyp-PTPN22 (a protein phosphatase negatively regulating T-cell activation) has been associated with autoimmunity. This work has investigated the possible association between PTPN22 C1858T (rs2476601) polymorphism and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) in a Colombian population. METHODS: A case-control study included 1,042 samples from 413 RA, 94 SLE and 101 SSc patients and 434 healthy controls. The TaqMan allele discrimination assay was used for genotyping. RESULTS: The case-control study provided robust evidence of association between allele 1858T and RA (p=5E-05), as well as between 1858T and SLE (p=0.004). These observations were confirmed for both diseases by meta-analysis (p=2E-04, pooled OR 1.9; 1.3-2.7 95% CI for RA; p<0.0001, pooled OR 2.8, 1.8-4.5 95% CI for SLE). No significant association was observed between 1858T and SSc (p=0.98, OR 1.11, 0.46-2.65 95% CI). CONCLUSIONS: The study suggested that the PTPN22 1858T variant influences RA and SLE genetic background but not that of SSc in the Colombian population.

[Evaluating the antimicrobial resistance on bacteria isolated iat a third-level hospital]. / Resistencia antimicrobiana de bacterias en un hospital de tercer nivel.

BACKGROUND: nosocomial infections are cause of morbidity and mortality and also increased costs. The aim was to evaluate the antimicrobial resistance in isolated clinical gram-positive and negative bacteria in a period of five years. METHODS: a retrospective descriptive epidemiological study was done. Analysis of antimicrobial resistance in bacteria Gram-positive and negative of 5117 clinical crops was done. Trend of proportions with Chi square (χ(2)) value of < 0.05 p was applied. RESULTS: the analyzed a sample crops, bacteria Gram-positive corresponded to 2622 (52.2 %) and bacteria gram negative to the 48.8 %. There is an increasing linear trend of resistance to antibiotics of Gram-positive: ciprofloxacin, clindamycin, chloramphenicol, erythromycin, streptomycin, penicillin, piperacillin / tazobactam, levofloxacin. For negative Gram: amoxicillin/clavulanic acid, aztreonam, cefazolin, cefepime, gatifloxacin, imipenem, piperacillin, tetracycline, ticarcillin clavulanic, trimethoprim/sulfamethoxazole, meropenem, levofloxacin. CONCLUSION: the increase of antimicrobial resistance forces to control the use of antibiotics drugs in the hospital behavior.

Adiponectin Influences FGF2 in the Developing Porcine Corpus Luteum.

Luteal angiogenesis is regulated by pro-angiogenic hormones including fibroblast growth factor 2 (FGF2) and angiopoietin 1 (Ang1), which are regulated by the adipokine leptin during development. Another adipokine, adiponectin, exhibits an inverse relationship with leptin and has been identified in the CL. Therefore, it is hypothesized that adiponectin will influence pro-angiogenic hormones in the developing porcine CL. Crossbred sows were randomly allocated to one of two days of the estrous cycle, day 5 (D5; n = 4) or day 7 (D7; n = 5) for CL collection. Tissue was processed for immunohistochemical localization of adiponectin receptor 2 (AdipoR2), gene expression of FGF2, Ang1, leptin, AdipoR2, and cell culture for adiponectin treatment. The expression of AdipoR2 tended (p = 0.09) to be higher in D7 lutea and was more prevalently localized to the cell surface of large and small luteal cells than in D5 tissue. Adiponectin influenced (p ≤ 0.05) FGF2, leptin, and AdipoR2 gene expression relative to the dose and day (D5 or D7). Collectively, the evidence supports the supposition that adiponectin influences angiogenic factors in the developing CL.

Optimization of phospholipid chemistry for improved lipid nanoparticle (LNP) delivery of messenger RNA (mRNA).

Lipid nanoparticles (LNPs) have been established as an essential platform for nucleic acid delivery. Efforts have led to the development of vaccines that protect against SARS-CoV-2 infection using LNPs to deliver messenger RNA (mRNA) coding for the viral spike protein. Out of the four essential components that comprise LNPs, phospholipids represent an underappreciated opportunity for fundamental and translational study. We investigated this avenue by systematically modulating the identity of the phospholipid in LNPs with the goal of identifying specific moieties that directly enhance or hinder delivery efficacy. Results indicate that phospholipid chemistry can enhance mRNA delivery by increasing membrane fusion and enhancing endosomal escape. Phospholipids containing phosphoethanolamine (PE) head groups likely increase endosomal escape due to their fusogenic properties. Additionally, it was found that zwitterionic phospholipids mainly aided liver delivery, whereas negatively charged phospholipids changed the tropism of the LNPs from liver to spleen. These results demonstrate that the choice of phospholipid plays a role intracellularly by enhancing endosomal escape, while also driving organ tropism in vivo. These findings were then applied to Selective Organ Targeting (SORT) LNPs to manipulate and control spleen-specific delivery. Overall, selection of the phospholipid in LNPs provides an important handle to design and optimize LNPs for improved mRNA delivery and more effective therapeutics.