Digital image analysis workflows for evaluation of cell behavior and tumor microenvironment to aid therapeutic assessment in high-risk neuroblastoma.

Digital pathology and artificial intelligence are promising emerging tools in precision oncology as they provide more robust and reproducible analysis of histologic, morphologic and topologic characteristics of tumor cells and the surrounding microenvironment. This study aims to develop digital image analysis workflows for therapeutic assessment in preclinical in vivo models. For this purpose, we generated pipelines that enable automatic detection and quantification of vitronectin and αvß3 in heterotopic high-risk neuroblastoma xenografts, demonstrating that digital analysis workflows can be used to provide robust detection of vitronectin secretion and αvß3 expression by malignant neuroblasts and to evaluate the possibility of combining traditional chemotherapy (etoposide) with extracellular matrix-targeted therapies (cilengitide). Digital image analysis added evidence for the relevance of territorial vitronectin as a therapeutic target in neuroblastoma, since its expression is modified after treatment, with a mean percentage of 60.44% in combined therapy tumors vs 45.08% in control ones. In addition, the present study revealed the efficacy of cilengitide for reducing αvß3 expression, with a mean αvß3 positivity of 34.17% in cilengitide treated material vs 66.14% in control and with less tumor growth when combined with etoposide, with a final mean volume of 0.04 cm3 in combined therapy vs 1.45 cm3 in control. The results of this work highlight the importance of extracellular matrix-focused therapies in preclinical studies to improve therapeutic assessment for high-risk neuroblastoma patients.

Dyskeratosis congenita: natural history of the disease through the study of a cohort of patients diagnosed in childhood.

Background: Dyskeratosis congenita (DC) is a multisystem and ultra-rare hereditary disease characterized by somatic involvement, bone marrow failure, and predisposition to cancer. The main objective of this study is to describe the natural history of DC through a cohort of patients diagnosed in childhood and followed up for a long period of time. Material and methods: Multicenter, retrospective, longitudinal study conducted in patients followed up to 24 years since being diagnosed in childhood (between 1998 and 2020). Results: Fourteen patients were diagnosed with DC between the ages of 3 and 17 years (median, 8.5 years). They all had hematologic manifestations at diagnosis, and nine developed mucocutaneous manifestations during the first decade of life. Seven presented severe DC variants. All developed non-hematologic manifestations during follow-up. Mutations were identified in 12 patients. Thirteen progressed to bone marrow failure at a median age of 8 years [range, 3-18 years], and eight received a hematopoietic stem cell transplant. Median follow-up time was 9 years [range, 2-24 years]. Six patients died, the median age was 13 years [range, 6-24 years]. As of November 2022, eight patients were still alive, with a median age of 18 years [range, 6-32 years]. None of them have developed myeloblastic syndrome or cancer. Conclusions: DC was associated with high morbidity and mortality in our series. Hematologic manifestations appeared early and consistently. Non-hematologic manifestations developed progressively. No patient developed cancer possibly due to their young age. Due to the complexity of the disease multidisciplinary follow-up and adequate transition to adult care are essential.

Influence of Monensin and Diflubenzuron on the Control of Immature Horn Fly and House Fly (Diptera: Muscidae) and Chemical Composition of Cattle Feces.

Twelve Angus × Hereford crossbred heifers were used in a completely randomized design to evaluate the effects of monensin and diflubenzuron feed additives on horn fly (Haematobia irritans) (L.) and house fly (Musca domestica) (L.) immature development. Heifers were randomly assigned to one of four treatment groups; 1) monensin fed at label rate, 2) diflubenzuron fed at label rate, 3) monensin and diflubenzuron fed at label rates together, and 4) nonsupplemented control. All treatments were administered from SD 0 to 28, followed by a 16-d wash-out period for a total study duration of 45 d and assayed to assess adult fly emergence, as well as fecal pH and fecal bacterial and total protein. A treatment × day interaction (P < 0.01) was observed for adult fly emergence. Fly emergence was not affected (P ≥ 0.05) by monensin, but was reduced during the 28 d treatment period when diflubenzuron was present (P = 0.01). Fecal pH, fecal bacterial protein, and total protein were not affected by any of the treatments (P ≥ 0.13). It is concluded that diflubenzuron is effective against both horn and house fly development regardless of the presence of monensin.

The sound of a Martian dust devil.

Dust devils (convective vortices loaded with dust) are common at the surface of Mars, particularly at Jezero crater, the landing site of the Perseverance rover. They are indicators of atmospheric turbulence and are an important lifting mechanism for the Martian dust cycle. Improving our understanding of dust lifting and atmospheric transport is key for accurate simulation of the dust cycle and for the prediction of dust storms, in addition to being important for future space exploration as grain impacts are implicated in the degradation of hardware on the surface of Mars. Here we describe the sound of a Martian dust devil as recorded by the SuperCam instrument on the Perseverance rover. The dust devil encounter was also simultaneously imaged by the Perseverance rover's Navigation Camera and observed by several sensors in the Mars Environmental Dynamics Analyzer instrument. Combining these unique multi-sensorial data with modelling, we show that the dust devil was around 25 m large, at least 118 m tall, and passed directly over the rover travelling at approximately 5 m s-1. Acoustic signals of grain impacts recorded during the vortex encounter provide quantitative information about the number density of particles in the vortex. The sound of a Martian dust devil was inaccessible until SuperCam microphone recordings. This chance dust devil encounter demonstrates the potential of acoustic data for resolving the rapid wind structure of the Martian atmosphere and for directly quantifying wind-blown grain fluxes on Mars.

Effects of lipopolysaccharide on follicular estrogen production and developmental competence in bovine oocytes.

Reproductive efficiency and female fertility is essential for productive and sustainable beef cattle operations. Gram-negative bacterial infections cause release of the endotoxin lipopolysaccharide (LPS) which initiates immune responses shown to alter ovarian steroidogenesis and impair oocyte development. The current study was designed to investigate the impact of varying levels of naturally occurring infection and follicular LPS on estradiol (E2) production and oocyte maturation. Bovine ovary pairs were harvested from a slaughterhouse, and oocytes were aspirated from small follicles and matured in vitro. Meiotic events were evaluated on nuclear maturation and spindle morphology to classify oocytes as normal or abnormal. Follicular fluid LPS concentrations were measured and subsequently separated into Low or High LPS groups. A marked difference was detected between the percent of abnormal oocytes matured from Low LPS follicles, compared to the percent of abnormal oocytes matured from High LPS follicles (P = 0.1). Follicular E2 concentrations tended to be greater for high LPS follicles (P = 0.1), however, relative abundance of mRNA transcripts for aromatase (P = 0.93) and beta-catenin (P = 0.63) were similar between groups. No changes were detected in Toll-like Receptor 4 (P = 0.15), Myeloid Differentiation Factor-2 (P = 0.61), or cluster of differentiation 14 (P = 0.46) mRNA transcript abundance in follicles with high LPS, compared to low. Therefore, even Low levels of follicular LPS indicating a subacute infection is capable of impacting the ovarian milieu and may represent an unappreciated factor leading to reduced female fertility and decreased cow retention.

The Effect of Horn Fly (Diptera: Muscidae) Infestation on Behavior, Water, and Feed Intake, and Digestion Characteristics of Beef Cattle.

Seven mature Angus × Hereford crossbreed cows (544 ± 23.2 kg of body weight) fitted with duodenal and ruminal cannulas were used in a crossover design to evaluate the effects of horn fly (Haematobia irritans) (L.) infestation on horn fly-induced defensive behaviors, feed and water intake, as well as digestion characteristics of beef cows. Cows were randomly assigned to one of two treatment groups: 1) a horn fly infested (1,000 flies per cow) or 2) a noninfested control group. All cows were housed in individual screened pens. Fly counts and infestations were performed daily to maintain consistent populations throughout the study. Sudan hay (11.4 % crude protein, dry matter basis) was selected to mimic forage quality that range cattle frequently graze in the southwest region. Horn fly-induced host defensive behaviors were greater (P ≤ 0.0002) for horn fly infested cattle. Intake of water, dry matter, organic matter, crude protein, and neutral detergent fiber were similar (P ≥ 0.4765) among infested and noninfested cows. However, total volatile fatty acid concentration tended to increase (P = 0.0967) when horn flies were present. Dry matter fecal excretion and total tract digestion were not affected (P ≥ 0.2602) by horn fly infestation. These data indicate that horn fly infestations do not affect forage intake or digestion characteristics of beef cattle (Bos taurus) in confinement settings.

[Sepsis Code: dodging mortality in a tertiary hospital]. / Código Sepsis: esquivando la mortalidad en un hospital terciario.

OBJECTIVE: In the hospital of La Princesa, the "Sepsis Code" (CSP) began in 2015, as a multidisciplinary group that provides health personnel with clinical, analytical and organizational tools, with the aim of the detection and early treatment of patients with sepsis. The objective of this study is to evaluate the impact of CSP implantation on mortality and to determine the variables associated with an increase in it. METHODS: A retrospective analytical study of patients with CSP alert activation from 2015 to 2018 was conducted. Clinical-epidemiological variables, analytical parameters, and severity factors such as admission to critical care units (UCC) and the need for amines were collected. Statistical significance was established at p < 0.05. RESULTS: We included 1,121 patients. The length of stay was 16 days and 32% required admission to UCC. Mortality showed a statistically significant linear downward trend from 24% in 2015 to 15% in 2018. The predictive mortality variables with statistically significant association were lactate > 2 mmol/L, creatinine > 1.6 mg/dL and the need for amines.>5.0%, mortality at the time of chart review 62.0%, and 6-months-post-discharge readmission 47.7%. CONCLUSIONS: The implementation of Sepsis Code decreases the mortality of patients with sepsis and septic shock. The presence of a lactate > 2 mmol/L, creatinine > 1.6 mg/dL and/or the need to administer amines in the first 24 hours, are associated with an increase in mortality in the patient with sepsis.

New vascular structure in broiler breast: breast-vessel.

Chickens intensively selected for accelerating growth rate and enhanced muscle mass has resulted in the occurrence of breast alterations with a negative consumers perception. Together with the already known breast abnormalities (White Striping, Wooden Breast and Spaghetti Meat) a new one has been described by the consumers as a "long and thin worm". For this reason, the aim of this work was to macroscopically and microscopically describe this structure in broiler breast. To this end, 2 different experiments were performed. In the first one, 4 broiler breasts from a supermarket were analysed. Thereafter, a second experiment was carried out on an experimental farm simulating field management conditions in order to confirm the results of the first experiment. To this end, 120 chickens were reared in an experimental farm up to 42 d. Breast samples were collected and analysed macroscopically and microscopically to assess the abnormality on the broiler breast. In both experiments, the results of the analysis showed the finding of tubular structures located on the surface of pectoralis major muscle compatible with arteries. So far, currently, this occurrence has not been described in the literature and we propose calling this new broiler breast feature as breast-vessel.

Assessment of reclaimed agro-wastewater polluted with insecticide residues for irrigation of growing lettuce (Lactuca sativa L) using solar photocatalytic technology.

Scientific literature is full of works studying the removal of different pollutants from water through different Advanced Oxidation Processes (AOPs). Many of them only suggest it is reused for agricultural purposes or for small crops in pots. This study is based on the reuse of reclaimed agricultural wastewater contaminated with four insecticides (chlorantraniliprole, imidacloprid, pirimicarb and thiamethoxam) for growing lettuce in field conditions. First, solar photocatalysis with TiO2/Na2S2O8 was used on a pilot plant in a sunny area (Murcia, SE of Spain) as an environmentally friendly technology to remove insecticide residues and their main reaction intermediates from contaminated water. The necessary fluence (H, kJ m-2) to accomplish 90% removal (H90) ranged from 0.12 to 1212 kJ m-2 for pirimicarb and chlorantraniliprole, respectively. Only six (derived from imidacloprid, pirimicarb and thiametoxam) of 18 transformation intermediate products studied were detected in reclaimed water during the photoperiod (2000 kJ m-2 of accumulated UVA radiation) although all of them were totally photodegraded after a fluence of 1250 kJ m-2. Secondly, reclaimed agro-wastewater was used to irrigate two lettuce crops grown under greenhouse conditions and under agricultural field conditions. In no cases, insecticide residues nor their TIPs were noticed above their respective LOQs (limits of quantification) in soil and lettuce samples (between 0.03 and 0.04 µg kg-1 for pirimicarb and 2.49 and 2.23 µg kg-1 for thiamethoxam, respectively) when they were irrigated with reclaimed water, while residues of the four insecticides and some of their intermediates were found in soil and lettuce by the end of cultivation when they were irrigated with non-reclaimed contaminated water. According to the results, this technology can be applied in a sustainable way, mainly in areas with water scarcity and high solar radiation, contributing to water utilisation in drought areas and the use of renewable energy.

Initial experience with 3D printing in the use of customized Nuss bars in pectus excavatum surgery. / Experiencia inicial en la impresión 3D para el uso de barras de Nuss personalizadas en la cirugía del pectus excavatum.

INTRODUCTION: Pectus excavatum (PE) surgical repair according to Nuss procedure is based on the intrathoracic insertion of one (or more) metallic bars for anatomical defect repair. Number of bars, bar length, bar shape, and thoracic insertion site are established during surgery, according to patient morphology, CT-scan, and especially the surgeon's experience. OBJECTIVE: To assess the usefulness of the design, simulation, and 3D printing of customized Nuss bars for each patient. MATERIAL AND METHODS: A prospective descriptive study of all patients undergoing PE surgery under 3D printing from June to December 2019 was carried out. Curvature, bar length, and optimal intercostal space were designed based on diagnostic CT-scan, and they were 3D printed full size. The resulting model was reproduced preoperatively on the usual prosthetic material, sterilized, and kept until surgery. RESULTS: The study cohort consisted of 6 patients. Median age was 15 years old (interquartile range: 14.25-15.25), median Haller index was 4.05 (interquartile range: 3.5-4.49), and repair index was 36.98% (interquartile range: 33.86-38.48%). A Nuss bar was introduced in all cases, without requiring removal or re-insertion. Median operating time was 79.5 minutes (interquartile range: 72.5-103). No postoperative complications were noted during follow-up (12 months). CONCLUSIONS: The preoperative design of Nuss bars with customized shape and size facilitates surgical planning. It also allows for the most optimal and accurate morphological repair possible, according to patient anatomy, thus reducing the risk of requiring removal and/or re-insertion, and therefore, of surgical complications.

INTRODUCCION: La corrección quirúrgica del pectus excavatum (PE) con técnica de Nuss, se basa en la inserción intratorácica de una (o más) barras metálicas para la corrección del defecto anatómico. El número de barras, su longitud, forma y punto de inserción torácico, se deciden durante la cirugía, según la morfología del paciente, el TC y, fundamentalmente, la experiencia del cirujano. OBJETIVO: Evaluar la utilidad del diseño, simulación e impresión 3D de barras de Nuss personalizadas para cada paciente. MATERIAL Y METODOS: Estudio descriptivo prospectivo, incluyendo a todos los pacientes intervenidos de PE bajo impresión 3D entre junio-diciembre 2019. Se diseñó la curvatura, longitud de la barra y espacio intercostal óptimo, en base al TC diagnóstico, y se imprimió en 3D en tamaño real. El modelo resultante se reprodujo prequirúrgicamente sobre material protésico habitual, se esterilizó y se reservó hasta la cirugía. RESULTADOS: Se recogieron 6 pacientes, mediana de edad 15 años (rango intercuartil 14,25-15,25 años). Mediana del Índice de Haller 4,05 (rango intercuartil 3,5-4,49) e índice de corrección 36,98% (rango intercuartil 33,86-38,48%). Se introdujo una barra de Nuss en todos los casos, sin precisar retirada ni reinserción. Mediana del tiempo quirúrgico 79,5 minutos (rango intercuartil 72,5-103 min). Ninguna complicación postquirúrgica durante el seguimiento (12 meses). CONCLUSIONES: El diseño prequirúrgico de la barra de Nuss, mediante forma y tamaño personalizados, facilita la planificación del procedimiento. A su vez, permite conseguir la corrección morfológica más óptima y precisa posible, según la anatomía del paciente, disminuyendo el riesgo de precisar retirada y/o reinserción de la barra, y por ende de complicaciones quirúrgicas.

Experiencia inicial en la impresión 3D para el uso de barras de Nuss personalizadas en la cirugía del pectus excavatum / Initial experience with 3D printing in the use of customized Nuss bars in pectus excavatum surgery

Introducción: La corrección quirúrgica del pectus excavatum (PE)con técnica de Nuss, se basa en la inserción intratorácica de una (o más)barras metálicas para la corrección del defecto anatómico. El númerode barras, su longitud, forma y punto de inserción torácico, se decidendurante la cirugía, según la morfología del paciente, el TC y, fundamentalmente, la experiencia del cirujano. Objetivos: Evaluar la utilidad del diseño, simulación e impresión3D de barras de Nuss personalizadas para cada paciente. Material y métodos: Estudio descriptivo prospectivo, incluyendoa todos los pacientes intervenidos de PE bajo impresión 3D entre junio-diciembre 2019. Se diseñó la curvatura, longitud de la barra y espaciointercostal óptimo, en base al TC diagnóstico, y se imprimió en 3D entamaño real. El modelo resultante se reprodujo prequirúrgicamente sobrematerial protésico habitual, se esterilizó y se reservó hasta la cirugía. Resultados. Se recogieron 6 pacientes, mediana de edad 15 años(rango intercuartil 14,25-15,25 años). Mediana del Índice de Haller4,05 (rango intercuartil 3,5-4,49) e índice de corrección 36,98% (rangointercuartil 33,86-38,48%). Se introdujo una barra de Nuss en todos loscasos, sin precisar retirada ni reinserción. Mediana del tiempo quirúrgico79,5 minutos (rango intercuartil 72,5-103 min). Ninguna complicaciónpostquirúrgica durante el seguimiento (12 meses). Conclusiones: El diseño prequirúrgico de la barra de Nuss, mediante forma y tamaño personalizados, facilita la planificación del procedimiento. A su vez, permite conseguir la corrección morfológica másóptima y precisa posible, según la anatomía del paciente, disminuyendoel riesgo de precisar retirada y/o reinserción de la barra, y por ende decomplicaciones quirúrgicas.(AU)

Introduction: Pectus excavatum (PE) surgical repair according toNuss procedure is based on the intrathoracic insertion of one (or more)metallic bars for anatomical defect repair. Number of bars, bar length,bar shape, and thoracic insertion site are established during surgery,according to patient morphology, CT-scan, and especially the surgeon’sexperience. Objective: To assess the usefulness of the design, simulation, and3D printing of customized Nuss bars for each patient. Materials and methods: A prospective descriptive study of all patients undergoing PE surgery under 3D printing from June to December2019 was carried out. Curvature, bar length, and optimal intercostalspace were designed based on diagnostic CT-scan, and they were 3Dprinted full size. The resulting model was reproduced preoperatively onthe usual prosthetic material, sterilized, and kept until surgery.Results. The study cohort consisted of 6 patients. Median age was15 years old (interquartile range: 14.25-15.25), median Haller indexwas 4.05 (interquartile range: 3.5-4.49), and repair index was 36.98%(interquartile range: 33.86-38.48%). A Nuss bar was introduced in allcases, without requiring removal or re-insertion. Median operating timewas 79.5 minutes (interquartile range: 72.5-103). No postoperative complications were noted during follow-up (12 months). Conclusions: The preoperative design of Nuss bars with custom-ized shape and size facilitates surgical planning. It also allows for themost optimal and accurate morphological repair possible, accordingto patient anatomy, thus reducing the risk of requiring removal and/orre-insertion, and therefore, of surgical complications.(AU)

Monitoring serologic response to single in ovo vaccination with an immune complex vaccine against infectious bursal disease in broilers.

The infectious bursal disease (IBD) virus is one of the most resistant and prevalent virus worldwide in the poultry industry, being vaccination the main tool to control the disease. For this reason, consistent and uniform immunization of broiler flocks against IBD is necessary to avoid the disease spreading. The aim of this study was to apply and assess an epidemiologic mapping tool focused on the immunization by in ovo single broiler vaccination using an immune complex IBD vaccine. With this regard, 7,576 serum samples were collected from 603 broiler flocks raised in 354 Spanish farms. To do so, blood samples were randomly collected from birds with ages between 35 to 51 d, and the serum was analyzed by ELISA. The results obtained from this study suggested a high uniform immunization against IBDV and a protective immunization between 35 and 51 d of age, with mean titer values ranging between 6,331 and 7,426. In addition, seroprevalence titer data of this large-scale monitoring study fitted a polynomial equation with a R2 value of 0.77, helping to explain and predict the humoral response to IBD vaccination. This seroprevalence map was applied to broiler production and was based on business intelligence tool that incorporates newly developed mapping tool to cover the need of having real-time information of humoral response to IBD vaccination and could be an effective tool for veterinary services to control and prevent IBD.

Family history of ochronotic arthropathy.

Alkaptonuria is a rare autosomal-recessive disorder that produces accumulation of homogentisic acid in body fluids. The accumulation in collagen tissues, mainly in the joint cartilage, produces ochronotic arthropathy. We report two clinical cases of one brother and sister with alkaptonuria and ochronotic arthropathy diagnosed in old age. In the first case, the patient is diagnosed by musculoskeletal involvement with long-term low back pain with other associated manifestations that made this pathology suspected. In the second case, the patient comes due to osteoporosis and other associated fractures and with the family history and the rest of the clinic, the appropriate complementary tests were performed and the diagnosis is established. It is unknown if there is consanguinity in these patients between parents or ancestors. It is an infrequent pathology that is often diagnosed intraoperatively. Despite the poor efficacy of medical treatment, it would be advisable to make an early diagnosis to avoid accumulation of the pigment and accelerated joint destruction and deposition in other locations. Owing to its prevalence, it is difficult to find a significant number of patients to search for new treatments that are intended to correct the enzyme deficit and not only to modify the elimination.

[Impact of the COVID-19 pandemic on the training of Spanish neurology residents]. / Repercusión de la pandemia por COVID-19 en la formación de los residentes de neurología españoles.

Introduction: The COVID-19 pandemic has transformed medical practice and severely disrupted the training of medical residents worldwide. The Spanish Society of Neurology conducted a study to assess its impact on the training of neurology residents in Spain. Methods: We performed a descriptive, cross-sectional study through a survey distributed by e-mail to all neurology residents belonging to the Society. The survey included questions on demographic variables, care activity, and personal and educational impact of the pandemic, as well as respondents' expectations for the future of their work in the post-pandemic era. Results: Of 422 surveys sent, we received a total of 152 responses (36%); 79 respondents (52%) were women and 73 (48%) were men. By year of residency, 51 respondents (33.6%) were in the fourth year, 45 (29.6%) in the third year, 28 (18.4%) in the second year, and 28 (18.4%) in the first year. A total of 139 respondents (90.8%) reported changes in hospital activity, and 126 (82.8%) considered the situation to have had a negative impact on their training, with 99 (64.7%) having lost non-recoverable rotations. Sixty-six percent of respondents (n=101) expressed a desire to extend their residency period. Conclusions: The pandemic has had an extremely severe impact on all areas of the health system, with trainee physicians being one of the most affected groups. Among neurology residents, the crisis has caused significant shortcomings in their training and clinical activities, through the suspension of specific rotations. A high percentage of respondents wished to extend the residency period.

Genotyping and molecular characterization of antimicrobial resistance in thermophilic Campylobacter isolated from poultry breeders and their progeny in Eastern Spain.

Thermophilic Campylobacter spp. are recognized as a major cause of acute bacterial diarrhea in humans, with broiler meat being the most common source of human infection. Antibiotic therapy is usually necessary for severe or prolonged infections, especially in immunocompromised populations such as young or elderly individuals. However, different studies have demonstrated a close association between antibiotic use in animal production and antimicrobial resistance (AMR) in humans. In this sense, there is social pressure to reduce antibiotic administration and find adequate alternatives to control the presence of bacterial infections in farms. However, there is a lack of information related to Campylobacter AMR dynamics through the entire production system from breeders to their progeny. It is unknown if resistance genes are a result of adaptation through chromosomal mutation or through horizontal gene transfer, instead of vertical transmission of DNA from the parent to their progeny. Thus, the main objectives of this study were to assess the main AMR rates present in a poultry production system, to study the relationship between Campylobacter AMR profiles from breeders and their progeny, and to study the presence and distribution of antibiotic resistance genes in poultry production. Regarding AMR rates, ciprofloxacin was classified as extremely high, followed by nalidixic acid and tetracyclines that were classified as very high. Moreover, this study demonstrated a relationship between the AMR patterns and genes found from Campylobacter strains isolated in breeders and those present in their progeny.

Crystalglobulinemia manifested as acute renal failure and thrombotic vasculopathy.

Crystalglobulinemia is an extremely rare pathology that is associated in most cases with plasma cell dyscrasia, mainly multiple myeloma. In most cases, it may be the manifestation of incipient gammopathy or it manifests shortly after diagnosis. We report a patient with ischemic lesions of thrombotic origin in lower limbs. Subsequently, renal involvement occurs, in view of this involvement, it is suspected that the patient may have an associated vasculitis. After performing the biopsy and with the subsequent diagnosis of monoclonal gammopathy of uncertain significance, the diagnosis is made. We review the most recent bibliography of patients who have been diagnosed with crystalglobulinemia associated with plasma dyscrasia focusing in those with thrombotic vasculopathy or acute renal failure. In our case, in addition to being associated with monoclonal gammopathy of undetermined significance that is less frequent, the debut of the symptoms is years before the detection of the monoclonal peak. This could speak of patients with a low peak of monoclonal component (not detected by immunoelectrophoresis) who could have kidney and vascular damage.

Features and applications of Ent35-MccV hybrid bacteriocin: current state and perspectives.

Bacteriocins are peptides of ribosomal synthesis that are active against bacteria related to the producing strain. They have been widely used in the food industry as biopreservatives. The generation of hybrid peptides by combining the genes that encode two different bacteriocins has made it possible to study the mechanisms of action of the bacteriocins that compose them and also develop new peptides with improved biotechnological applications. Hybrid bacteriocins may be obtained in several ways. In our laboratory, by combining enterocin CRL35 and microcin V (Ent35-MccV), we obtained a broad-spectrum peptide that is active against both Gram-positive and Gram-negative bacteria. Ent35-MccV is sensitive to the action of intestinal proteases and is heat resistant, which makes it a good candidate for use as a biopreservative. For this reason, the peptide was tested in skim milk and beef burgers as food models. We also obtained more potent variants of the hybrid by modifying the central amino acid of the hinge region that connects the two bacteriocins. This review also discusses future applications and perspectives regarding the Ent35-MccV and other hybrid peptides.Key Points• Ent35-MccV is a new broad-spectrum bacteriocin.• The mechanism of action of bacteriocins can be studied using hybrid peptides.• Genetic engineering allows obtaining improved bacteriocin derivatives.• Hybrid peptides can be used in the food, pharmaceutical, and veterinary applications.