Cloacaenodin, an Antimicrobial Lasso Peptide with Activity against Enterobacter.

Using genome mining and heterologous expression, we report the discovery and production of a new antimicrobial lasso peptide from species related to the Enterobacter cloacae complex. Using NMR and mass spectrometric analysis, we show that this lasso peptide, named cloacaenodin, employs a threaded lasso fold which imparts proteolytic resistance that its unthreaded counterpart lacks. Cloacaenodin has selective, low micromolar, antimicrobial activity against species related to the E. cloacae complex, including species implicated in nosocomial infections and against clinical isolates of carbapenem-resistant Enterobacterales. We further used site-directed mutagenesis to probe the importance of specific residues to the peptide's biosynthesis, stability, and bioactivity.

Foville syndrome: a neurological emergency of clinical relevance. case report

Introduction: Foville syndrome (inferior medial pontine syndrome) is a clinical entity that makes part of a subclassification of a broader category of posterior circulation stroke. It is characterized by a blockage of the basilar artery caused by lesions in the pontine tegmentum. This syndrome has a very low incidence worldwide, but its clinical relevance is considerable. Case report: A 41-year-old patient without any medical history was admitted to the emergency department due to signs of focal neurologic deficits. Imaging findings were compatible with an ischemic lesion in the brainstem, and cerebral angiography showed involvement of the basilar artery territory. The patient was diagnosed and followed up in the intensive care unit (ICU) until his recovery. Conclusion: Foville syndrome is a rare disease with high morbidity and mortality. Early recognition and a multidisciplinary approach are decisive to improve the patient's prognosis.

Introducción. El síndrome de Foville (síndrome pontino medial inferior) es una entidad clínica que hace parte de una subclasificación de la categoría más amplia de eventos cerebrovasculares de la circulación posterior, se presenta como resultado de la oclusión de la arteria basilar debido a lesiones en el tegmento pontino. Este síndrome tiene una muy baja incidencia a nivel mundial, pero es de gran relevancia clínica. Presentación del caso. Hombre de 41 años sin antecedentes patológicos, que ingresó al servicio de urgencias por signos de focalización neurológica. Sus hallazgos imagenológicos fueron compatibles con una lesión isquémica en el tronco encefálico y la angiografía cerebral evidenció un compromiso en el territorio de la arteria basilar. El paciente fue diagnosticado y se le dio seguimiento en la unidad de cuidados intensivos (UCI) hasta su rehabilitación. Conclusión. El síndrome de Foville es una enfermedad infrecuente y de alta mortalidad. El reconocimiento temprano de esta afección y un abordaje multidisciplinario son determinantes para mejorar el pronóstico del paciente.

Folliculin-interacting protein FNIP2 impacts on overweight and obesity through a polymorphism in a conserved 3' untranslated region.

BACKGROUND: Overweight and obesity are defined by an anomalous or excessive fat accumulation that may compromise health. To find single-nucleotide polymorphisms (SNPs) influencing metabolic phenotypes associated with the obesity state, we analyze multiple anthropometric and clinical parameters in a cohort of 790 healthy volunteers and study potential associations with 48 manually curated SNPs, in metabolic genes functionally associated with the mechanistic target of rapamycin (mTOR) pathway. RESULTS: We identify and validate rs2291007 within a conserved region in the 3'UTR of folliculin-interacting protein FNIP2 that correlates with multiple leanness parameters. The T-to-C variant represents the major allele in Europeans and disrupts an ancestral target sequence of the miRNA miR-181b-5p, thus resulting in increased FNIP2 mRNA levels in cancer cell lines and in peripheral blood from carriers of the C allele. Because the miRNA binding site is conserved across vertebrates, we engineered the T-to-C substitution in the endogenous Fnip2 allele in mice. Primary cells derived from Fnip2 C/C mice show increased mRNA stability, and more importantly, Fnip2 C/C mice replicate the decreased adiposity and increased leanness observed in human volunteers. Finally, expression levels of FNIP2 in both human samples and mice negatively associate with leanness parameters, and moreover, are the most important contributor in a multifactorial model of body mass index prediction. CONCLUSIONS: We propose that rs2291007 influences human leanness through an evolutionarily conserved modulation of FNIP2 mRNA levels.

Caracterización epidemiológica y clínica de los pacientes intervenidos en una cirugía de revascularización miocárdica / Epidemiological and clinical characterization of patients undergoing myocardial revascularization surgery

Resumen Introducción: La cardiopatía isquémica es un problema de salud pública y puede tratarse por medio de la revascularización miocárdica. Objetivo: Estructurar el primer perfil epidemiológico y clínico de los pacientes intervenidos en Tolima. Materiales y método: Es un estudio de corte transversal, de 183 pacientes mayores de 18 años programados para revascularización miocárdica entre septiembre de 2018 y septiembre de 2019. Se eligieron variables clínicas y demográficas. Se realizó un análisis descriptivo, un análisis bivariado para mortalidad y circulación extracorpórea, y una regresión logística para la mortalidad intrahospitalaria. Resultados: La edad media de los pacientes fue de 66.7 años y un 68.85% correspondió a la población femenina. Se presentó HA en 80.33%, tabaquismo en 49.18%, dislipidemia en 44.81% y DM en 40.98%. Se registró mayor proporción de complicaciones en los pacientes intervenidos sin CEC, como complicaciones pulmonares, FA de novo y una estancia intrahospitalaria y posoperatoria mayor. Los pacientes que fallecieron tuvieron mayor proporción de complicaciones, mayor estancia hospitalaria, mayor cantidad de reintervenciones y tiempo de ventilación mecánica. El modelo de regresión reveló una relación con mortalidad para los pacientes que tuvieron requerimiento de diálisis (OR = 8.7) complicaciones pulmonares (OR = 10.5) y desarrollo de FA de novo (OR = 11.3). Conclusiones: Este estudio caracteriza a la población para generar marcos de referencia en un grupo poco estudiado como el tolimense. De modo adicional, se presentaron mejores desenlaces en los pacientes llevados a revascularización miocárdica con circulación extracorpórea, y unas relaciones claras de mortalidad y complicaciones posoperatorias.

Abstract Introduction: The ischemic cardiopathy is a public health issue, that can be treated with a coronary artery bypass grafting (CABG). Objective: To present the first clinical and epidemiological profile of CABG treated patients in Tolima, Colombia. Materials and method: We conduct a cross sectional study, including 183 patients driven to a CABG procedure, between September 2018-2019. We chose clinical and demographic variables. And posteriorly, performed a descriptive and bivariate analysis, including mortality and extracorporeal circulation. Besides, we completed a logistic regression for intrahospital mortality. Results: The average age of our patients was 66,7 years, and 68.85% were female. They presented in an 80.33% arterial hypertension, smoked an 49.18%, had dyslipidemia and diabetes 44.81% and 40.95% respectively. There were more complications in patients who were drove into on pump CABG, primarily pulmonary complications, atrial fibrillation, mayor intrahospital and post-operatory stay. The patients who died, present more complications, intrahospital stay, reinterventions and mechanic ventilation time. Our regression model evidenced mortality association with post-operatory dialysis (OR = 8.7), pulmonary complications (OR = 10.5) and new atrial fibrillation (OR = 11.3). Conclusions: This study aim to characterize the Tolima's population, creating a reference in this less studied population. On the other side, the study discuss the better outcomes in patients taken to myocardial bypass with extracorporeal membrane oxygenation. And the association between dead and certain postoperative complications.

Cutaneous myiasis in skin cancer and malignant wounds: a systematic review.

BACKGROUND: Cutaneous myiasis in patients with malignant wounds or skin cancer is a rare and undesirable event with limited epidemiological data. A subregister of reports, lack of education in the population, inadequate empirical treatments, and medical underestimation are components of a public health problem that threatens patients' lives. METHODS: We conducted a systematic review of the literature of cutaneous myiasis associated with malignant wounds and skin cancer, characterizing sociodemographic variables, risk factors, clinical and histological features, and treatment. Additionally, we present a demonstrative case with the adequate taxonomic evaluation. DISCUSSION: Cutaneous myiasis is an underestimated and poorly managed infestation, which can generate severe complications in oncological patients. This is the first systematic review in the literature about this clinical scenario, which provides information to the physician and clinical researcher about the epidemiological gaps and what has been published so far. CONCLUSIONS: Findings from the current review have helped to display the sociodemographic, epidemiological, and clinical behavior of myiasis in skin cancer and malignant wounds. Its contribution to the greater tumor tissue destruction is clear; however, more studies are required. The therapeutic management in these patients is equally clarified.

Association of calcium and dairy product consumption with childhood obesity and the presence of a Brain Derived Neurotropic Factor-Antisense (BDNF-AS) polymorphism.

BACKGROUND & AIMS: Calcium and dairy products have multiple health benefits. The objective of this work was to evaluate the association between calcium/dairy intake, blood pressure, the BDNF-AS rs925946 polymorphism and nutritional status in a group of schoolchildren. METHODS: As part of the GENYAL study to childhood obesity prevention, 221 children belonging to different areas of the Community of Madrid were enrolled. Anthropometric and dietary data were collected, and children were genotyped according to the rs925946 polymorphism. Adjusted logistic and linear models were used to describe the data. RESULTS: A significantly lower consumption of calcium in overweight versus normal weight children was observed (811.0 ± 174.1; 859.0 ± 195.9; 954.0 ± 223.1 mg; for obesity, overweight and normal weight, respectively, p = 0.010). Moreover, an inverse association between blood pressures and calcium intake was detected (ß = -0.006 (-0.011, -3e-4)), p = 0.040. The number of dairy servings/day showed a protective effect against overweight (OR = 0.48 (0.29, 0.75), p = 0.001). Finally, common homozygous children (GG) showed an inverse association between the calcium intake and the BMI (ß = -0.003 (-0.006, -0.001), p = 0.004), which was not observed in children carrying the T allele (ß = -1.3e-4 (-0.0022, 0.0024), p = 0.93). CONCLUSION: Calcium and dairy were strongly associated with the nutritional status and blood pressure. The identification of differential effects of calcium/dairy consumption on the nutritional status according to genetics may contribute to the personalization of future nutritional advice. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.govNCT03419520.

Relapsing polychondritis, an underestimated dermatological urgency: case report and literature review.

BACKGROUND: Relapsing polychondritis is an autoimmune multisystemic disease with primary chondral involvement. Its high mortality and morbidity make it a real clinical challenge. CASE DESCRIPTION: A 32-year-old woman with a history of relapsing polychondritis, refractory to multiple treatments, with multisystem compromise, imminent risk of death due to severe tracheobronchial damage and difficult ventilatory support, and successful treatment with infliximab. DISCUSSION AND EVALUATION: Several treatments have been described in the literature, such as nonsteroidal anti-inflammatory drugs, corticosteroids, dapsone, azathioprine, cyclosporine, cyclophosphamide, and methotrexate. However, the cases refractory to conventional therapy may lead to chronicity, irreversibility, and death. As a result, a third-line therapy could improve the prognosis of these patients. CONCLUSIONS: Biological therapy is a good option for disease control and quality of life improvement. In addition, the physician should consider these treatments to avoid the chronicity and risk of death of these patients.

Lesión cútanea por mycobacterium avium intracelular / Mycobacterium avium intracellulare

Mycobacterium avium intracelular (MAC) es una de las micobacterias más comúnmente encontradas en casos de infección por VIH. Su frecuencia ha disminuido en gran medida con la terapia antirretroviral altamente activa (HAART) y el uso de antibióticos profilácticos. El compromiso de la piel es muy raro. Se han descrito pápulas, nódulos, úlceras y placas verrucosas. Se reporta el caso clínico de un hombre inmunocomprometido con lesión cutánea única por Mycobaterium avium intracelular.