[Long-term clinical and radiological results of metatarsophalangeal resection arthroplasty in patients with large forefoot deformities]. / Resultados clínicos y radiológicos a largo plazo de la artroplastía de resección metatarsofalángica en pacientes con grandes deformidades del antepié.

INTRODUCTION: metatarsophalangeal resection arthroplasty is considered a salvage surgical procedure able to improve the quality of life of patients with major forefoot deformities. MATERIAL AND METHODS: a retrospective observational study of 31 patients (36 feet) with major forefoot deformities operated at our institution was performed. Thirty two feet required additional surgery involving the first ray, most of them (72.2%) through MTP joint fusion. The mean follow-up period was 10.3 ± 4.6 years. Most patients were women (87.1%), the mean age was 74.2 ± 11.5 years. RESULTS: at the final follow-up, mean AOFAS score was 77.9 ± 10.2 points and mean MOxFQ score was 18.3 ± 8.3 points. Visual analog scale (VAS) for pain improved significantly from 7.5 ± 1.2 points to 3.4 ± 2.1 points on average. Good clinical results were also reported on ability to put on shoes comfortably. The mean resection arthroplasty spaces at the end of the study were 1.3, 1.8, 2.5 and 4.4 mm, for second to fifth rays, respectively. The mean sizes of remodeling osteophytes at the end of the study were 1.6, 1.4, 1.1 and 0.7 mm, respectively. Significant improvement was also achieved in the hallux valgus angle (HVA) and intermetatarsal angle (IMA) at the end of the study. CONCLUSION: in our experience, metatarsophalangeal resection arthroplasty continues to be a valid choice in patients with major forefoot deformities, with satisfactory long-term clinical and radiographic results.

INTRODUCCIÓN: la artroplastía de resección metatarsofalángica se considera un procedimiento quirúrgico de salvamento capaz de mejorar la calidad de vida de pacientes con deformidades importantes en el antepié. MATERIAL Y MÉTODOS: se realizó un estudio observacional retrospectivo de 31 pacientes (36 pies) con deformidades importantes en el antepié operados en nuestra institución. Treinta y dos pies requirieron cirugía adicional que involucró el primer metatarsiano, la mayoría de ellos (72.2%) a través de la fusión de la articulación metatarsofalángica. El período de seguimiento promedio fue 10.3 ± 4.6 años. La mayoría de los pacientes fueron mujeres (87.1%), con una edad promedio de 74.2 ± 11.5 años. RESULTADOS: en la última visita de seguimiento, la puntuación AOFAS promedio fue de 77.9 ± 10.2 puntos y la puntuación MOxFQ promedio fue de 18.3 ± 8.3 puntos. La escala visual analógica (EVA) para el dolor mejoró significativamente, pasando de 7.5 ± 1.2 puntos a 3.4 ± 2.1 puntos de media. También se constataron buenos resultados clínicos en cuanto a la capacidad de calzarse con comodidad. Los espacios de resección promedio al final del estudio fueron 1.3, 1.8, 2.5 y 4.4 mm para el segundo al quinto radio, respectivamente. Los tamaños promedio de los osteofitos por remodelación al final del estudio fueron de 1.6, 1.4, 1.1 y 0.7 mm, respectivamente. También se logró una mejora significativa en el ángulo de hallux valgus (AHV) y en el ángulo intermetatarsiano (IMA) al final del estudio. CONCLUSIÓN: en nuestra experiencia, la artroplastía de resección metatarsofalángica sigue siendo una opción válida en pacientes con deformidades graves del antepié, con resultados clínicos y radiográficos satisfactorios a largo plazo.

First Mexican Consensus on Crohn's disease.

INTRODUCTION: Crohn's disease (CD) is a subtype of chronic and incurable inflammatory bowel disease. It can affect the entire gastrointestinal tract and its etiology is unknown. OBJECTIVE: The aim of this consensus was to establish the most relevant aspects related to definitions, diagnosis, follow-up, medical treatment, and surgical treatment of Crohn's disease in Mexico. MATERIAL AND METHODS: Mexican specialists in the areas of gastroenterology and inflammatory bowel disease were summoned. The consensus was divided into five modules, with 69 statements. Applying the Delphi panel method, the pre-meeting questions were sent to the participants, to be edited and weighted. At the face-to-face meeting, all the selected articles were shown, underlining their level of clinical evidence; all the statements were discussed, and a final vote was carried out, determining the percentage of agreement for each statement. RESULTS: The first Mexican consensus on Crohn's disease was produced, in which recommendations for definitions, classifications, diagnostic aspects, follow-up, medical treatment, and surgical treatment were established. CONCLUSIONS: Updated recommendations are provided that focus on definitions, classifications, diagnostic criteria, follow-up, and guidelines for conventional medical treatment, biologic therapy, and small molecule treatment, as well as surgical management.

Avelumab to treat Merkel cell carcinoma: real-life experience in a dedicated oncology center. / Avelumab en el tratamiento del carcinoma de células de Merkel: experiencia en vida real en un centro monográfico oncológico.

The arrival of immunotherapy has revolutioned the management of patients with metastatic Merkel cell carcinoma (MCC). We conducted an observational, retrospective study of 14 cases treated with avelumab. The response rate was 57%: complete response was reached in 29% of patients, and partial responses in 29%. The drug proved effective in 83% (5/6) of the patients with a single metastatic site. However, the disease progressed in 75% (3/4) of the patients with bone metastases. PD1-L expression, MCC polyomavirus (MCPyV) positivity, and an impaired neutrophil-to-lypmhocyte ratio (NLR) could not be associated with responses to the therapy. Avelumab is an effective and safe drug for the management of advanced MCC, and its effectiveness appears to be impacted by the number and location of metastases.

Retrospective analysis of regional anaesthesia in hip surgery: A clinical audit.

INTRODUCTION: Total hip arthroplasty is one of the most frequent surgical interventions in the hospital setting. Nonetheless, the ideal method to manage post-operative pain is still unknown. Multimodal analgesia techniques based on regional anaesthesia are amongst the most promising solutions. OBJECTIVES: The aim of this study was to evaluate postoperative pain after total hip arthroplasty according to whether peripheral nerve block was performed (femoral block, fascia iliaca block and pericapsular nerve group block). Intravenous morphine consumption during the patient's stay in the post-anaesthesia care unit was measured, as well as the number of opioid rescues at 24 and 48 h post intervention. As secondary objectives, the prevalence of nerve injury, prolonged quadricipital block, and morphine consumption were established according to other variables of interest. MATERIALS AND METHODS: In this observational retrospective study, data was collected from the electronic medical record of 656 traumatological surgery patients from April 2018 to August 2020, with the following inclusion criteria: over 18 years old, ASA I-III, primary total hip arthroplasty under general anaesthesia or subarachnoid anaesthesia (only with hyperbaric bupivacaine) and use of levobupivacaine for peripheral nerve block. RESULTS: A total of 362 patients were selected. The main surgical indication was coxarthrosis (61.3%), followed by hip fracture (22.6%). Peripheral nerve blocks were performed on 169 patients (66.3% femoral, 27.7% PENG, and 6.0% fascia iliaca). Mean postoperative opioid consumption in PACU was lower in patients in who received a PENG (2.2 mg) or a femoral (3.27 mg) block, compared to those who received neither (6.69 mg). There were no differences in opioid rescues at 24 and 48 h after the procedure. Nerve injury incidence was low (.8%), and not associated with nerve blocks. The incidence of prolonged quadricipital paralysis was also low (1.3%), and was mainly associated with femoral nerve block (75% of cases). CONCLUSIONS: This retrospective study supports the use of regional blocks as opioid-sparing techniques, highlighting their role in rapid functional recovery with no motor impairment.

A copper(ii) peptide helicate selectively cleaves DNA replication foci in mammalian cells.

The use of copper-based artificial nucleases as potential anticancer agents has been hampered by their poor selectivity in the oxidative DNA cleavage process. An alternative strategy to solve this problem is to design systems capable of selectively damaging noncanonical DNA structures that play crucial roles in the cell cycle. We designed an oligocationic CuII peptide helicate that selectively binds and cleaves DNA three-way junctions (3WJs) and induces oxidative DNA damage via a ROS-mediated pathway both in vitro and in cellulo, specifically at DNA replication foci of the cell nucleus, where this DNA structure is transiently generated. To our knowledge, this is the first example of a targeted chemical nuclease that can discriminate with high selectivity 3WJs from other forms of DNA both in vitro and in mammalian cells. Since the DNA replication process is deregulated in cancer cells, this approach may pave the way for the development of a new class of anticancer agents based on copper-based artificial nucleases.

Rab18 Drift in Lipid Droplet and Endoplasmic Reticulum Interactions of Adipocytes under Obesogenic Conditions.

The adipose tissue stores excess energy in the form of neutral lipids within adipocyte lipid droplets (LDs). The correct function of LDs requires the interaction with other organelles, such as the endoplasmic reticulum (ER) as well as with LD coat-associated proteins, including Rab18, a mediator of intracellular lipid trafficking and ER-LD interaction. Although perturbations of the inter-organelle contact sites have been linked to several diseases, such as cancer, no information regarding ER-LD contact sites in dysfunctional adipocytes from the obese adipose tissue has been published to date. Herein, the ER-LD connection and Rab18 distribution at ER-LD contact sites are examined in adipocytes challenged with fibrosis and inflammatory conditions, which represent known hallmarks of the adipose tissue in obesity. Our results show that adipocytes differentiated in fibrotic conditions caused ER fragmentation, the expansion of ER-LD contact sites, and modified Rab18 dynamics. Likewise, adipocytes exposed to inflammatory conditions favored ER-LD contact, Rab18 accumulation in the ER, and Rab18 redistribution to large LDs. Finally, our studies in human adipocytes supported the suggestion that Rab18 transitions to the LD coat from the ER. Taken together, our results suggest that obesity-related pathogenic processes alter the maintenance of ER-LD interactions and interfere with Rab18 trafficking through these contact sites.

Validation of electrodeposited 241Am alpha-particle sources for use in liquified gas detectors at cryogenic temperatures.

This paper describes a procedure for the validation of alpha-particle sources (exempt unsealed sources) to be used in experimental setups with liquefied gases at cryogenic temperatures (down to -196 °C) and high vacuum. These setups are of interest for the development and characterization of neutrino and dark matter detectors based on liquid argon, among others. Due to the high purity requirements, the sources have to withstand high vacuum and cryogenic temperatures for extended periods. The validation procedure has been applied to 241Am sources produced by electrodeposition.

Estimating the direct costs of oral cancer in Spain: a retrospective hospital data analysis.

BACKGROUND: Studies on the costs incurred from cancer in Spain are scarce and have focused on the most prevalent types such as colorectal, breast, and lung cancer. The aim of this study was to calculate the direct costs associated with the diagnostic, treatment and follow-up procedures for oral cancer in Spain. MATERIAL AND METHODS: Applying a bottom-up approach, we retrospectively analyzed the medical records of a cohort of 200 patients with oral cancer (C00-C10), diagnosed and treated in Spain between 2015 and 2017. For each patient, we collected their age, sex, degree of medical impairment (American Society of Anesthesiologists [ASA] classification), tumor extent (TNM classification), relapses and survival during the first 2 years of follow-up. The final calculation of the costs is expressed in absolute values in euros as the percentage of the gross domestic product per capita and in international dollars (I$). RESULTS: The total cost per patient rose to €16,620 (IQR, €13,726; I$11,634), and the total direct cost at the national level was €136,084,560 (I$95,259,192). The mean cost for oral cancer represented 65.1% of the gross domestic product per capita. The costs for the diagnostic and therapeutic procedures were determined by the ASA grade, tumor size, lymph node infiltration and presence of metastases. CONCLUSIONS: The direct costs for oral cancer are considerable compared with other types of cancer. In terms of gross domestic product, the costs were similar to those of countries neighboring Spain, such as Italy and Greece. The main determinants of this economic burden were the patient's degree of medical impairment and tumor extent.

3D bioprinted functional skeletal muscle models have potential applications for studies of muscle wasting in cancer cachexia.

Acquired muscle diseases such as cancer cachexia are responsible for the poor prognosis of many patients suffering from cancer. In vitro models are needed to study the underlying mechanisms of those pathologies. Extrusion bioprinting is an emerging tool to emulate the aligned architecture of fibers while implementing additive manufacturing techniques in tissue engineering. However, designing bioinks that reconcile the rheological needs of bioprinting and the biological requirements of muscle tissue is a challenging matter. Here we formulate a biomaterial with dual crosslinking to modulate the physical properties of bioprinted models. We design 3D bioprinted muscle models that resemble the mechanical properties of native tissue and show improved proliferation and high maturation of differentiated myotubes suggesting that the GelMA-AlgMA-Fibrin biomaterial possesses myogenic properties. The electrical stimulation of the 3D model confirmed the contractile capability of the tissue and enhanced the formation of sarcomeres. Regarding the functionality of the models, they served as platforms to recapitulate skeletal muscle diseases such as muscle wasting produced by cancer cachexia. The genetic expression of 3D models demonstrated a better resemblance to the muscular biopsies of cachectic mouse models. Altogether, this biomaterial is aimed to fabricate manipulable skeletal muscle in vitro models in a non-costly, fast and feasible manner.

Impact of M Dwarfs Ultraviolet Radiation on Prebiotic Chemistry: The Case of Adenine.

To date, several exoplanets have been found to orbit within the habitable zone of main sequence M stars (M dwarfs). These stars exhibit different levels of chromospheric activity that produces ultraviolet (UV) radiation. UV may be harmful to life, but it can also trigger reactions of prebiotic importance on the surface of a potentially habitable planet (PHP). We created a code to obtain the adenine yield for a known adenine synthesis route from diaminomaleonitrile (DAMN). We used computational methods to calculate the reaction coefficient rates (photolysis rate J and rate constant K) for the intermediate molecules DAMN, diaminofumaronitrile (DAFN), and 4-aminoimidazole-5-carbonitrile (AICN) of the adenine synthesis route. We used stellar UV sources and a mercury lamp to compare the theoretical results with experiments performed with lamps. The surface UV flux of planets in the habitable zone of two active M dwarfs (Proxima Centauri and AD Leonis) and the prebiotic Earth was calculated using the photochemical model ATMOS, considering a CO2-N2-H2O atmosphere. We obtained UV absorption coefficients for DAMN and DAFN and thermodynamic parameters that are useful for prebiotic chemistry studies. According to our results, experiments using UV lamps may underestimate the photolysis production of molecules of prebiotic importance. Our results indicate that photolysis reactions are fast with a yield of 50% of AICN in 10 s for the young Sun and ∼1 h for Proxima Centauri b. Planets around active M dwarfs may provide the most favorable environment for UV-mediated production of compounds relevant to the origins of life. The kinetic reaction AICN + HCN  adenine is the bottleneck of the pathway with reaction rates <10-22 L/(mol·s).

Gastric herniation due to rupture of diaphragmatic prosthesis in the postoperative period of pleuropneumonectomy due to mesothelioma: A complication to consider.

Extrapleural pneumonectomy, usually associated with pericardial and diaphragmatic reconstruction with prosthetic material, is one of the surgical techniques used in the treatment of malignant pleural mesothelioma. Herniation of the abdominal viscera towards the thorax through the prosthetic material at the diaphragmatic level is a rare but potentially serious complication of these procedures, which must be diagnosed quickly for urgent repair. We present the case of a patient who presented with gastric herniation in the early postoperative period of a left pneumonectomy due to pleural mesothelioma. The clinical findings were mild, but supported by imaging tests, they confirmed the diagnostic hypothesis and facilitated the solution of the condition. Possible contributing factors are reviewed and the need for early diagnosis and treatment is emphasized to avoid ischemia of herniated abdominal viscera in the thoracic cavity, due to the risk of necrosis and contamination by fecaloid material.

Microcirugía endodóntica: regeneración ósea guiada en defecto óseo tunelizado: caso clínico / Endodontic microsurgery: guided bone regeneration in a through-and-through bone defect: a clinical case

Se presentó a la Cátedra de Endodoncia de la Facultad de Odontología de la Universidad de Buenos Aires un paciente masculino de 62 años de edad que al examen clínico presentaba una fístula vestibular en la zona de la pieza 1.2 y dolor a la percusión. Al examen radiográ-fico se identificó una lesión apical extensa abarcando las piezas dentarias 1.2 y 1.1 endodónticamente trata-das con alteración severa de la anatomía del espacio endodóntico, así como la presencia de postes metáli-cos que no respetaban el eje del canal radicular. Ante el análisis tomográfico se observó una perforación de la pieza 1.2 y una lesión periapical extensa afectando ambas corticales (vestibular y palatina). Se decidió un abordaje microquirúrgico con técnicas de regenera-ción ósea guiada (ROG) y se realizaron los controles clínico-tomográficos a los 6, 12 y 24 meses. Por otro lado, se evaluó con micromografía de rayos X la ana-tomía de los ápices radiculares resecados. La lesión extirpada fue analizada histológicamente (AU)

A 62-year-old male patient attended the Endodontics department of the Buenos Aires University. He was examined clinically and a vestibular fistula in 1.2 area and pain under percussion were found. Radiographic examination identified an extended periapical lesion compromising teeth 1.2 and 1.1 with endodontic treatment severely altering the root canal anatomy, as well as metallic cast posts that did not preserve root canal axis. Regarding the tomographic analysis, a vestibular root perforation was observed (1.2), and both, vestibular and palatal corticals, were affected. We decided to perform a surgical approach with guided bone regeneration techniques (GBR). Clinical-CBCT controls were done at 6, 12 and 24 months. Furthermore, the anatomy of the resected root apex-es was evaluated with X ray microtomography. The removed lesion was histologically analyzed (AU)

New ultrasound-guided capsular blocks for hip surgery: A narrative review.

Surgery on the hip joint is very common. Improving pain management has been and is one of the fundamental pillars to optimize the functional recovery of patients. To do this, we must design a multimodal anesthetic-analgesic plan that covers the entire perioperative period. Peripheral nerve blocks and fascial blocks are an important component of multimodal analgesic strategies. Traditional blocks have moderate efficacy, prolonged motor impairment, and increased risk of falls. As an alternative, capsular blocks ("ileopsoas plane block" or "IPB" and pericapsular nerve group block or "PENG block") have recently been described that aim to avoid motor impairment while maintaining optimal analgesic efficacy. The objective of this review is to describe the new capsular blocks and to analyze whether they allow to improve postoperative analgesia and promote functional recovery with fewer complications, based on the innervation of the hip. To do this, a bibliographic review was carried out in the PubMed, Embase and Cochrane Library databases from January 2018 to June 2020.

Conformational dynamics in the disordered region of human CPEB3 linked to memory consolidation.

BACKGROUND: Current understanding of the molecular basis of memory consolidation points to an important function of amyloid formation by neuronal-specific isoforms of the cytoplasmic polyadenylation element binding (CPEB) protein family. In particular, CPEB is thought to promote memory persistence through formation of self-sustaining prion-like amyloid assemblies at synapses, mediated by its intrinsically disordered region (IDR) and leading to permanent physical alterations at the basis of memory persistence. Although the molecular mechanisms by which amyloid formation takes place in CPEB have been described in invertebrates, the way amyloid formation occurs in the human homolog CPEB3 (hCPEB3) remains unclear. Here, we characterize by NMR spectroscopy the atomic level conformation and ps-ms dynamics of the 426-residue IDR of hCPEB3, which has been associated with episodic memory in humans. RESULTS: We show that the 426-residue N-terminal region of hCPEB3 is a dynamic, intrinsically disordered region (IDR) which lacks stable folded structures. The first 29 residues, M1QDDLLMDKSKTQPQPQQQQRQQQQPQP29, adopt a helical + disordered motif, and residues 86-93: P83QQPPPP93, and 166-175: P166PPPAPAPQP175 form polyproline II (PPII) helices. The (VG)5 repeat motif is completely disordered, and residues 200-250 adopt three partially populated α-helices. Residues 345-355, which comprise the nuclear localization signal (NLS), form a modestly populated α-helix which may mediate STAT5B binding. These findings allow us to suggest a model for nascent hCPEB3 structural transitions at single residue resolution, advancing that amyloid breaker residues, like proline, are a key difference between functional versus pathological amyloids. CONCLUSION: Our NMR spectroscopic analysis of hCPEB3 provides insights into the first structural transitions involved in protein-protein and protein-mRNA interactions. The atomic level understanding of these structural transitions involved in hCPEB3 aggregation is a key first step toward understanding memory persistence in humans, as well as sequence features that differentiate beneficial amyloids from pathological ones. AREAS: Biophysics, Structural Biology, Biochemistry & Neurosciences.

Neurofibromatosis laríngea: a propósito de un caso / Laryngeal neurofibromatosis: a case report

Resumen El neurofibroma laríngeo es poco frecuente, representa menos del 0,1% de las neoplasias benignas de la laringe. Puede presentarse aislado, o más comúnmente asociado a neurofibromatosis tipo I. Se presenta el caso de un paciente varón de 40 años, ya diagnosticado de neurofibromatosis tipo I, que presenta masa supraglótica submucosa asintomática, diagnosticada como hallazgo casual en una intubación por una cirugía previa programada.

Abstract Laryngeal neurofibroma is rare, representing less than 0.1% of benign tumors of the larynx. It can occur in isolation or more commonly associated with type I neurofibromatosis. The case of a 40-year-old male patient, already diagnosed with type I neurofibromatosis, is presented with an asymptomatic submucosal supraglottic mass, diagnosed as a chance finding in intubation due to a previous scheduled surgery.

Real-world analysis of main clinical outcomes in patients with polycythemia vera treated with ruxolitinib or best available therapy after developing resistance/intolerance to hydroxyurea.

BACKGROUND: Ruxolitinib is approved for patients with polycythemia vera (PV) who are resistant/intolerant to hydroxyurea, but its impact on preventing thrombosis or disease-progression is unknown. METHODS: A retrospective, real-world analysis was performed on the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to subsequent treatment with ruxolitinib (n = 105) or the best available therapy (BAT; n = 272). Survival probabilities and rates of thrombosis, hemorrhage, acute myeloid leukemia, myelofibrosis, and second primary cancers were calculated according to treatment. To minimize biases in treatment allocation, all results were adjusted by a propensity score for receiving ruxolitinib or BAT. RESULTS: Patients receiving ruxolitinib had a significantly lower rate of arterial thrombosis than those on BAT (0.4% vs 2.3% per year; P = .03), and this persisted as a trend after adjustment for the propensity to have received the drug (incidence rate ratio, 0.18; 95% confidence interval, 0.02-1.3; P = .09). There were no significant differences in the rates of venous thrombosis (0.8% and 1.1% for ruxolitinib and BAT, respectively; P = .7) and major bleeding (0.8% and 0.9%, respectively; P = .9). Ruxolitinib exposure was not associated with a higher rate of second primary cancers, including all types of neoplasia, noncutaneous cancers, and nonmelanoma skin cancers. After a median follow-up of 3.5 years, there were no differences in survival or progression to acute leukemia or myelofibrosis between the 2 groups. CONCLUSIONS: The results suggest that ruxolitinib treatment for PV patients with resistance/intolerance to hydroxyurea may reduce the incidence of arterial thrombosis. LAY SUMMARY: Ruxolitinib is better than other available therapies in achieving hematocrit control and symptom relief in patients with polycythemia vera who are resistant/intolerant to hydroxyurea, but we still do not know whether ruxolitinib provides an additional benefit in preventing thrombosis or disease progression. We retrospectively studied the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to whether they subsequently received ruxolitinib (n = 105) or the best available therapy (n = 272). Our findings suggest that ruxolitinib could reduce the incidence of arterial thrombosis, but a disease-modifying effect could not be demonstrated for ruxolitinib in this patient population.

Controlling oncogenic KRAS signaling pathways with a Palladium-responsive peptide.

RAS oncoproteins are molecular switches associated with critical signaling pathways that regulate cell proliferation and differentiation. Mutations in the RAS family, mainly in the KRAS isoform, are responsible for some of the deadliest cancers, which has made this protein a major target in biomedical research. Here we demonstrate that a designed bis-histidine peptide derived from the αH helix of the cofactor SOS1 binds to KRAS with high affinity upon coordination to Pd(II). NMR spectroscopy and MD studies demonstrate that Pd(II) has a nucleating effect that facilitates the access to the bioactive α-helical conformation. The binding can be suppressed by an external metal chelator and recovered again by the addition of more Pd(II), making this system the first switchable KRAS binder, and demonstrates that folding-upon-binding mechanisms can operate in metal-nucleated peptides. In vitro experiments show that the metallopeptide can efficiently internalize into living cells and inhibit the MAPK kinase cascade.

Stereoselective Self-Assembly of DNA Binding Helicates Directed by the Viral ß-Annulus Trimeric Peptide Motif.

Combining coordination chemistry and peptide engineering offers extraordinary opportunities for developing novel molecular (supra)structures. Here, we demonstrate that the ß-annulus motif is capable of directing the stereoselective assembly of designed peptides containing 2,2'-bipyridine ligands into parallel three-stranded chiral peptide helicates, and that these helicates selectively bind with high affinity to three-way DNA junctions.

Chemical characterization (LC-MS-ESI), cytotoxic activity and intracellular localization of PAMAM G4 in leukemia cells.

Generation 4 of polyamidoamine dendrimer (G4-PAMAM) has several biological effects due to its tridimensional globular structure, repetitive branched amides, tertiary amines, and amino-terminal subunit groups liked to a common core. G4-PAMAM is cytotoxic due to its positive charges. However, its cytotoxicity could increase in cancer cells due to the excessive intracellular negative charges in these cells. Furthermore, this work reports G4-PAMAM chemical structural characterization using UHPLC-QTOF-MS/MS (LC-MS) by electrospray ionization to measure its population according to its positive charges. Additionally, the antiproliferative effects and intracellular localization were explored in the HMC-1 and K-562 cell lines by confocal microscopy. The LC-MS results show that G4-PAMAM generated multivalent mass spectrum values, and its protonated terminal amino groups produced numerous positive charges, which allowed us to determine its exact mass despite having a high molecular weight. Additionally, G4-PAMAM showed antiproliferative activity in the HMC-1 tumor cell line after 24 h (IC50 = 16.97 µM), 48 h (IC50 = 7.02 µM) and 72 h (IC50 = 5.98 µM) and in the K-562 cell line after 24 h (IC50 = 15.14 µM), 48 h (IC50 = 14.18 µM) and 72 h (IC50 = 9.91 µM). Finally, our results showed that the G4-PAMAM dendrimers were located in the cytoplasm and nucleus in both tumor cell lines studied.

Carotid glomus in childhood: presentation of a clinical case. / Glomus carotídeo en la infancia. Presentación de un caso clínico.

INTRODUCTION: Carotid glomus is an exceptional extra-adrenal paraganglioma in childhood originating at the carotid body. Only 3% of paragangliomas occur in the head and the neck. Familial forms, associated with Succinate Dehydrogenase (SDH) gene mutations, account for 10% of cases, the proportion being higher in childhood. They are benign in 95% of patients, but they can extend to both carotids. Treatment is surgical with or without previous embolization. Metastasis is rare and associated with malignant cases, which are limited. CLINICAL CASE: 8-year-old patient with a cervical mass originating 4 months ago and normal serum levels. Regarding family history, she had an aunt who underwent cervical surgery. Ultrasound examination demonstrated a greatly vascularized hypoechoic mass most likely related to carotid glomus. Full surgical resection without embolization was decided upon, which proved uneventful. The genetic study was positive for SDH gene mutation. CONCLUSION: Carotid glomus in childhood should be considered as a differential diagnosis in cervical masses. Surgical treatment without previous embolization represents a safe therapeutic option in selected cases.

INTRODUCCION: El glomus carotídeo es un paraganglioma extraadrenal, excepcional en la infancia, cuyo origen es el cuerpo carotídeo. Solo el 3% de los paragangliomas se presentan en cabeza y cuello. Existe un 10% de formas familiares asociadas a mutaciones en el gen de la succinato deshidrogenasa (SDH), porcentaje que es mayor en la infancia. Son tumores benignos en un 95% de los pacientes, pero pueden afectar por extensión a ambas carótidas. Su tratamiento es quirúrgico con o sin embolización previa. Las metástasis son raras y están asociadas a los escasos casos de malignidad. CASO CLINICO: Paciente de 8 años de edad con masa cervical de 4 meses de evolución, serologías normales. Como antecedente destaca una tía sometida a cirugía cervical. Ecográficamente se objetiva masa hipoecoica muy vascularizada en probable relación con glomus carotídeo. Se decide resección quirúrgica sin embolización que resulta completa y sin incidencias. Estudio genético positivo para la mutación en el gen de la SDH. CONCLUSION: El glomus carotídeo en la infancia ha de ser tenido en cuenta como diagnóstico diferencial en masas cervicales. El tratamiento quirúrgico sin embolización previa es una opción terapéutica segura en casos seleccionados.