Mesenchymal stem cells induce an immunosuppressive microenvironment in pituitary tumors.

BACKGROUND: The tumor microenvironment (TME) includes diverse cellular components such as mesenchymal stem cells (MSC) and immune cells among others. MSC have been isolated from different tumors and they favor tumor cell growth, however, their role in pituitary tumors (PT) remains unknown. Herein we report the presence of MSCs in 2 ACTH-secreting PT causing Cushing disease (MCU), 2 nonfunctioning adenomas of gonadotrope differentiation (MNF) and 2 non tumoral pituitary glands (MS). METHODS: We have analyzed their transcriptomic profiles by RNAseq and compared MSC in terms of their immunosuppressive effects against lymphoid T cell and macrophage populations by means of co-cultures and flow cytometry. RESULTS: Our transcriptomic analysis revealed molecular differences between MSC derived from non-tumoral pituitaries and MSC derived from PT. Two distinct subpopulations of MSC, one displaying immunosuppressive properties and the other with increased pro-proliferative capabilities, regardless of their origin. MSC derived from ACTH- and nonfunctioning PT, but not those derived from non-tumoral glands significantly inhibited the proliferation of activated T cells, favored the generation of Tregs and promote M2 macrophage polarization. Such immunosuppressive effects were correlated with an upregulation of programmed death ligand 1 and intracellular expression of macrophage colony stimulating factor (M-CSF) and IL-10. Importantly, MSC derived from ACTH-PT showed a higher immunosuppressive potential than MSC isolated from nonfunctioning tumors. CONCLUSION: This study demonstrates the presence of at least two MSC subpopulations in the pituitary gland and suggests that immunosuppressive effects of MSC may have important implications in PT growth.

Mitochondrial quality control in non-exudative age-related macular degeneration: From molecular mechanisms to structural and functional recovery.

Non-exudative age-related macular degeneration (NE-AMD) is the leading blindness cause in the elderly. Clinical and experimental evidence supports that early alterations in macular retinal pigment epithelium (RPE) mitochondria play a key role in NE-AMD-induced damage. Mitochondrial dynamics (biogenesis, fusion, fission, and mitophagy), which is under the central control of AMP-activated kinase (AMPK), in turn, determines mitochondrial quality. We have developed a NE-AMD model in C57BL/6J mice induced by unilateral superior cervical ganglionectomy (SCGx), which progressively reproduces the disease hallmarks circumscribed to the temporal region of the RPE/outer retina that exhibits several characteristics of the human macula. In this work we have studied RPE mitochondrial structure, dynamics, function, and AMPK role on these parameters' regulation at the nasal and temporal RPE from control eyes and at an early stage of experimental NE-AMD (i.e., 4 weeks post-SCGx). Although RPE mitochondrial mass was preserved, their function, which was higher at the temporal than at the nasal RPE in control eyes, was significantly decreased at 4 weeks post-SCGx at the same region. Mitochondria were bigger, more elongated, and with denser cristae at the temporal RPE from control eyes. Exclusively at the temporal RPE, SCGx severely affected mitochondrial morphology and dynamics, together with the levels of phosphorylated AMPK (p-AMPK). AMPK activation with metformin restored RPE p-AMPK levels, and mitochondrial dynamics, structure, and function at 4 weeks post-SCGx, as well as visual function and RPE/outer retina structure at 10 weeks post-SCGx. These results demonstrate a key role of the temporal RPE mitochondrial homeostasis as an early target for NE-AMD-induced damage, and that pharmacological AMPK activation could preserve mitochondrial morphology, dynamics, and function, and, consequently, avoid the functional and structural damage induced by NE-AMD.

Diversity of oncopharmacogenetic profile within Spanish population.

Consensus guidelines for genotype-guided fluoropyrimidine dosing based on variation in the dihydropyrimidine dehydrogenase (DPYD) gene before treatment have been firmly established. The prior pharmacogenetic report avoids the serious toxicity that inevitably occurred in a non-negligible percentage of the treated patients. The precise description of the allelic distribution of the variants of interest in our reference populations is information of great interest for the management of the prescription of these antineoplastic drugs. We characterized the allelic distribution of the UGT1A1*28 variant (rs3064744), as well as the DPYD*2A (rs3918290) variant, c.1679T>G (rs55886062), c.2846A>T (rs67376798) and c.1129-5923C>G (rs75017182; HapB3) in series of 5251 patients who are going to receive treatment with irinotecan and fluoropyrimidines, representative of Valencian, Aragonese and Western Andalusian populations.

Mitochondrial Mechanisms in Immunity and Inflammatory Conditions: Beyond Energy Management.

Significance: The growing importance of mitochondria in the immune response and inflammation is multifaceted. Unraveling the different mechanisms by which mitochondria have a relevant role in the inflammatory response beyond the energy management of the process is necessary for improving our understanding of the host immune defense and the pathogenesis of various inflammatory diseases and syndromes. Critical Issues: Mitochondria are relevant in the immune response at different levels, including releasing activation molecules, changing its structure and function to accompany the immune response, and serving as a structural base for activating intermediates as NLRP3 inflammasome. In this scientific journey of dissecting mitochondrial mechanisms, new questions and interesting aspects arise, such as the involvement of mitochondrial-derived vesicles in the immune response with the putative role of preventing uncontrolled situations. Recent Advances: Researchers are continuously rethinking the role of mitochondria in acute and chronic inflammation and related disorders. As such, mitochondria have important roles as centrally positioned signaling hubs in regulating inflammatory and immune responses. In this review, we present the current understanding of mitochondrial mechanisms involved, beyond the largely known mitochondrial dysfunction, in the onset and development of inflammatory situations. Future Directions: Mitochondria emerge as an interesting and multifaceted platform for studying and developing pharmaceutical and therapeutic approaches. There are many ongoing studies aimed to describe the effects of specific mitochondrial targeted molecules and treatments to ameliorate the consequences of exacerbated inflammatory components of pathologies and syndromes, resulting in an open area of increasing research interest.

No increase in the CTG repeat size during transmission from parent with expanded allele: false suspicion of contraction phenomenon.

Objectives: Myotonic dystrophy type 1 (DM1), also known as Steinert's disease, is a chronic, progressive and disabling multisystemic disorder with a broad spectrum of severity that arises from an autosomal-dominant expansion of the Cytosine-Thymine-Guanine (CTG) triplet repeat in the 3' untranslated region of the DMPK gene (19q13.3). Case presentation: In this study, we report the case of a family with several intergenerational expansions of the CTG repeat, with an additional case of a false suspicion of contraction phenomenon due to TP-PCR limitations. Conclusions: The meiotic instability of the (CTG)n repeats leads to genetic anticipation where increased size of DM1 mutation and a more severe phenotype have been reported in affected individuals across generations. Even if extremely rare, a decrease in the CTG repeat size during transmission from parents to child can also occur, most frequently during paternal transmissions.

Hyperhomocysteinemia in hypofertile male patients can be alleviated by supplementation with 5MTHF associated with one carbon cycle support.

Introduction: Homocysteine (Hcy) is a cellular poison, side product of the hydrolysis of S-Adenosyl Homocysteine, produced after the universal methylation effector S -Adenosylmethionine liberates a methyl group to recipient targets. It inhibits the methylation processes and its rising is associated with multiple disease states and ultimately is both a cause and a consequence of oxidative stress, affecting male gametogenesis. We have determined hyper homocysteinhemia (HHcy) levels can be reliably reduced in hypofertile patients in order to decrease/avoid associated epigenetic problems and protect the health of future children, in consideration of the fact that treatment with high doses of folic acid is inappropriate. Methods: Homocysteine levels were screened in male patients consulting for long-standing infertility associated with at least three failed Assisted Reproductive Technology (ART) attempts and/or repeat miscarriages. Seventy-seven patients with Hcy levels > 15 µM were treated for three months with a combination of micronutrients including 5- MethylTetraHydroFolate (5-MTHF), the compound downstream to the MTHFR enzyme, to support the one carbon cycle; re-testing was performed at the end of a 3 months treatment period. Genetic status for Methylenetetrahydrofolate Reductase (MTHFR) Single nucleotide polymorphisms (SNPs) 677CT (c.6777C > T) and 1298AC (c.1298A > C) was determined. Results: Micronutrients/5-MTHF were highly efficient in decreasing circulating Hcy, from averages 27.4 to 10.7 µM, with a mean observed decrease of 16.7 µM. The MTHFR SNP 677TT (homozygous form) and combined heterozygous 677CT/1298AC status represent 77.9% of the patients with elevated Hcy. Discussion: Estimation HHcy should not be overlooked in men suffering infertility of long duration. MTHFR SNPs, especially 677TT, are a major cause of high homocysteinhemia (HHcy). In these hypofertile patients, treatment with micronutrients including 5-MTHF reduces Hcy and even allows spontaneous pregnancies post treatment. This type of therapy should be considered in order to ensure these patients' quality of life and avoid future epigenetic problems in their descendants.

mRNA COVID-19 Vaccination Does Not Exacerbate Symptoms or Trigger Neural Antibody Responses in Multiple Sclerosis.

BACKGROUND AND OBJECTIVE: In people with multiple sclerosis (pwMS), concern for potential disease exacerbation or triggering of other autoimmune disorders contributes to vaccine hesitancy. We assessed the humoral and T-cell responses to SARS-CoV-2 after mRNA vaccination, changes in disease activity, and development of antibodies against central or peripheral nervous system antigens. METHODS: This was a prospective 1-year longitudinal observational study of pwMS and a control group of patients with other inflammatory neurologic disorders (OIND) who received an mRNA vaccine. Blood samples were obtained before the first dose (T1), 1 month after the first dose (T2), 1 month after the second dose (T3), and 6 (T4), 9 (T5), and 12 (T6) months after the first dose. Patients were assessed for the immune-specific response, annualized relapse rate (ARR), and antibodies to onconeuronal, neural surface, glial, ganglioside, and nodo-paranodal antigens. RESULTS: Among 454 patients studied, 390 had MS (22 adolescents) and 64 OIND; the mean (SD) age was 44 (14) years; 315 (69%) were female; and 392 (87%) were on disease-modifying therapies. Antibodies to the receptor-binding domain were detected in 367 (86%) patients at T3 and 276 (83%) at T4. After a third dose, only 13 (22%) of 60 seronegative patients seroconverted, and 255 (92%) remained seropositive at T6. Cellular responses were present in 381 (93%) patients at T3 and in 235 (91%) patients at T6 including all those receiving anti-CD20 therapies and in 79% of patients receiving fingolimod. At T3 (429 patients) or T6 (395 patients), none of the patients had developed CNS autoantibodies. Seven patients had neural antibodies that were already present before immunization (3 adult patients with MS had MOG-IgG, 2 with MG and 1 with MS had neuronal cell surface antibodies [unknown antigen], and 1 with MS had myelin antibody reactivity [unknown antigen]. Similarly, no antibodies against PNS antigens were identified at T3 (427 patients). ARR was lower in MS and not significantly different in patients with OIND. Although 182 (40%) patients developed SARS-CoV-2 infection, no cases of severe COVID-19 or serious adverse events occurred. DISCUSSION: In this study, mRNA COVID-19 vaccination was safe and did not exacerbate the autoimmune disease nor triggered neural autoantibodies or immune-mediated neurologic disorders. The outcome of patients who developed SARS-CoV-2 infection was favorable.

Association Between VDR and CYP24A1 Polymorphisms, Atopic Dermatitis, and Biochemical Lipid and Vitamin D Profiles in Spanish Population: Case-Control Study.

BACKGROUND: Atopic dermatitis (AD) is the most prevalent inflammatory skin disorder, characterized by impaired epidermal barrier function and an altered immune response, both of which are influenced by vitamin D deficiency. Single-nucleotide polymorphisms (SNPs) in VDR and CYP24A1 have been previously associated with AD. OBJECTIVE: We sought to characterize the associations between the VDR and CYP24A1 polymorphisms and the vitamin D and lipid biochemical profile in children diagnosed with AD. METHODS: A total of 246 participants (143 patients with AD and 103 healthy controls) were enrolled in this study. Genotyping for polymorphisms in VDR (rs2239185, rs1544410, rs7975232, rs2238136, rs3782905, rs2239179, rs1540339, rs2107301, rs2239182, and rs731236) and CYP24A1 (rs2248359 and rs2296241) was performed by allele-specific polymerase chain reaction using integrated fluidic circuit technology. Serum levels of calcium, phosphorus, and vitamin D were measured, and the biochemical lipid profile was determined. RESULTS: Among VDR SNPs, rs2239182 exerted a protective effect against the development of AD, whereas rs2238136 was identified as a risk factor for AD. The GCC haplotype (rs2239185-G, rs1540339-C, and rs2238136-C) appeared to protect against the development of AD. rs2239182-CC was associated with higher 25(OH)D concentrations, whereas rs2238136-TT, rs2239185-GA, and rs2248359-TT were present in a large proportion of patients with serum vitamin D deficiency. rs2239185-AA, rs2239182-CC, and rs1540339-CC were associated with higher serum total cholesterol; rs2239182-TT was associated with lower low-density lipoprotein cholesterol; and rs2239182-TC with lower high-density lipoprotein cholesterol. Both CYP24A1 SNPs (rs2296241-AA and rs2248359-TT) were associated with higher high-density lipoprotein cholesterol levels. CONCLUSIONS: The VDR SNP rs2238136 is a risk factor for AD and other SNPs in VDR and CYP24A1, which may lead to alterations in biochemical parameters that influence the risk of AD. Our findings highlight the complex genetic basis to AD and indicate that interrelationships between different genetic factors can lead to alterations in vitamin D metabolism or lipid profiles, which in turn may influence the development of AD.

First case of very late-onset FHL2 in Spain with two variants in the PRF1 gene.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but fatal disorder characterized by the proliferation and infiltration of macrophages and hyperactivated T lymphocytes that escape from the physiological control pathways and favour the existence of an environment of excessive inflammation and tissue destruction. HLH has been classified into two types: a primary or familial autosomal recessive form, caused by mutations in genes encoding proteins involved in the granule-dependent cytotoxic pathway (familial hemophagocytic lymphohistiocytosis [FHL] types 1-5); and other secondary or acquired form, generally associated with infections, malignancy, autoimmune diseases, metabolic disorders or primary immunodeficiencies. Since the first familial hemophagocytic lymphohistiocytosis-2 (FHL2) causative mutation in the PRF1 gene was described in 1999, more than 200 mutations have been identified to date. Here, we report the first case of very late-onset FHL2 in a Spanish 72-year-old female with splenomegaly, hypertriglyceridemia, hypofibrinogenemia, pancytopenia and marrow hemophagocytosis harbouring in heterozygosity two PRF1 variants proposed as causative in this study. The heterozygous mutation c.445G>A (p.Gly149Ser) identified in the exon 2 results in a missense mutation previously described as a probable pathogenic variant associated with the development of FHL2. Affecting the same exon, c.272C>T (p.Ala91Val) is the most prevalent variant of this gene. Although it was initially classified as benign, recent studies support its potential pathogenic role, considering it a variant of uncertain significance associated with a risk of developing FHL2. The genetic confirmation of FHL made possible an adequate counselling to the patient and direct relatives and provided important information for her control and follow-up.

Spinocerebellar ataxia type 15 caused by missense variants in the ITPR1 gene.

BACKGROUND AND PURPOSE: Spinocerebellar ataxia type 15 (SCA15) is a degenerative, adult onset autosomal dominant cerebellar ataxia, caused almost exclusively by deletions in the inositol 1,4,5 triphosphate receptor type 1 (ITPR1) gene (ITPR1). ITPR1 mediates calcium release from the endoplasmic reticulum, and particularly abounds in Purkinje cells. It plays a pivotal role in excitatory and inhibitory actions on Purkinje cells, and alterations in their balance cause cerebellar dysfunction in ITPR1 knockout mice. To date, only two single missense mutations have been reported to cause SCA15. They were considered pathogenic because cosegregation occurred with disease, and haploinsufficiency was hypothesized as their pathogenic mechanism. METHODS: In this study, three Caucasian kindreds with different heterozygous missense variants in ITPR1 are reported. The main clinical manifestation was a slowly progressive gait ataxia with onset after 40 years of age, with chorea in two patients and hand tremor in another one, concordant with manifestations found in SCA15. RESULTS: The three missense variants identified in ITPR1 were c.1594G>A; p.(Ala532Thr) in Kindred A, c.56C>T; p.(Ala19Val) in Kindred B, and c.256G>A; p.(Ala86Thr) in Kindred C. Every variant was labelled as of unknown significance; however, each one cosegregated with disease and was predicted to be pathogenic by in silico tests. CONCLUSIONS: The three ITPR1 missense variants found in this study exhibited cosegregation with disease, a result that sustains their pathogenicity. Further studies are needed to confirm the role of missense mutations in SCA15.

Hereditary hemochromatosis: An update vision of the laboratory diagnosis.

Haemochromatosis (HC) is an inherited disorder of iron metabolism. The 85-90% of Hereditary hemochromatosis cases are caused by mutations in HFE gene (HC type 1). The remaining 10-15% of HC cases are caused by mutations in other non-HFE genes (HJV, HAMP, TRF2, SLC40A1, BMP6). The study of patients for the diagnosis of HC has an important laboratory approached: analysis of biochemical parameters and genetic studies. To confirm a case, it is necessary to carry out a genetic study of the C282Y and H63D mutations. The presence of C282Y mutation in homozygosis is compatible with the diagnosis of HC type 1. Due to the incomplete penetrance of this mutation and the variable phenotypic expression, the severe forms of the disease are relatively rare. The study of variants in non-HFE genes allows more detailed study of both non-classic HC cases and those with more severe clinical expression. The genotype characterization of a patient not always justified the phenotype expression of the symptoms in this disease. All laboratory clinicians must consider recommendation provide by the experts in the Materia.

CSF1R-related Adult-onset Leukoencephalopathy: The First Reported Case in Spain.

Colony-stimulating factor 1 receptor-related adult-onset leukoencephalopathy is a primary microgliopathy characterized by a complex phenotype, which can be easily misdiagnosed with other leukoencephalopathy and neurodegenerative diseases such as frontotemporal dementia. It is estimated to be the most common adult-onset leukodystrophy. Here, we report the case of a 67-year-old man with a history of progressive impairment of behavioral and cognitive functions, including apathy, inhibition, tendency to mutism, and deficits in complex planning skills. Neurological examination revealed pyramidalism in the lower limbs. Brain imaging showed symmetrical confluent frontal leukoencephalopathy, bilateral frontal calcifications, and thinning of the corpus callosum. The diagnosis was confirmed by the identification of a heterozygous pathogenic variant in the colony-stimulating factor 1 receptor. As far as we know, this is the first documented case in Spain. In this paper, we aim to expand on clinical features and underline the importance of brain imaging for the diagnosis of an entity that we consider to be underdiagnosed.

Extrauterine Retroperitoneal Leiomyomas: 3 Case Reports and Review of the Literature.

Leiomyomas are benign mesenchymal tumors which originate from smooth muscle cells. Extrauterine leiomyomas are rare and they may arise where smooth muscle cells are found. Their diagnosis is challenging due to their heterogeneous ways of presentation. Histological analysis may reveal areas of sarcomatous differentiation; therefore, complete resection of the entire tumor is the only curative treatment. There is no adjuvant therapy proved to increase overall survival. It is essential to develop a standardized protocol, detailing how to follow up these patients since it is not reported in the literature to date; however, it is advisable to follow them because the local recurrence rate is high if small implants remain. In this review, we present 3 cases of extrauterine leiomyomas diagnosed and treated in our hospital. The management was different in each case, highlighting the heterogeneity of this condition. According to the literature, there are no solid guidelines on their management. We compare our experience with the data available to date in order to support the existing knowledge and provide our expertise for future studies.

Mitochondrial H2O2 metabolism as central event of heart complex I syndrome in early diabetes.

Hydrogen peroxide is the main metabolite effective in redox regulation and it is considered an insulinomimetic agent, with insulin signalling being essential for normal mitochondrial function in cardiomyocytes. Therefore, the aim of this work was to deeply analyse the heart mitochondrial H2O2 metabolism, in the early stage of type 1 diabetes. Diabetes was induced by Streptozotocin (STZ, single dose, 60 mg × kg-1, ip.) in male Wistar rats and the animals were sacrificed 10 days after injection. Mitochondrial membrane potential and ATP production, using malate-glutamate as substrates, in the heart of diabetic animals were like the ones observed in control group. Mn-SOD activity was lower (15%) in the heart of diabetic rats even though its expression was increased (29%). The increment in heart mitochondrial H2O2 production (117%) in diabetic animals was accompanied by an enhancement in the activities and expressions of glutathione peroxidase (26% and 42%) and of catalase (200% and 133%), with no changes in the peroxiredoxin activity, leading to [H2O2]ss ∼40 nM. Heart mitochondrial lipid peroxidation and protein nitration were higher in STZ-injected animals (45% and 42%) than in control group. The mitochondrial membrane potential and ATP production preservation suggest the absence of irreversible damage at this early stage of diabetes 1. The increase in mitochondrial [H2O2]ss above the physiological range, but still below supraphysiological concentration (∼100 nM) seems to be part of the adaptive response triggered in cardiomyocytes due to the absence of insulin. The signs of mitochondrial dysfunction observed in this very early stage of diabetes are consistent with the mitochondrial entity called ″complex I syndrome″.

Microdeleciones del gen AZF en varones azoospérmicos-oligozoospérmicos / AZF gene microdeletions in azoospermic–oligozoospermic males

Antecedentes y objetivo: La presencia de microdeleciones en las regiones del factor de azoospermia (AZF) del cromosoma Y (YCM) se considera la causa genética más frecuente de infertilidad masculina junto con el síndrome de Klinefelter. El objetivo del estudio fue investigar las frecuencias y tipo de YCM en hombres infértiles en Aragón y analizar la relación entre las hormonas sexuales, la concentración espermática y las microdeleciones en ellos.Pacientes y métodosEstudio descriptivo retrospectivo de 644 varones, durante el periodo 2006-2019, a los que se les realizo el cribado para YCM mediante YChromStrip (Operón, España) por PCR+hibridación reversa, espermiograma, cariotipo y medición de las hormonas sexuales.ResultadosLa frecuencia de YCM fue del 3,88% (25/644), no detectándose en ningún paciente con oligozoospermia leve ni normospérmico, es decir, en recuentos espermáticos superiores a 5×106/ml. El grupo de pacientes azoospérmicos fue el que presentó una frecuencia de YCM más elevada (14,58%, 14/96). Las deleciones en la región AZFc fueron las más frecuentes (68%). El 20% (5/25) de pacientes con YCM presentó además algún tipo de anomalía en el cariotipo que incluyeron aneuploidías, deleciones, duplicaciones o translocaciones. La concentración espermática fue significativamente menor y las concentraciones de FSH y LH significativamente mayores en el grupo de pacientes con YCM.ConclusionesEl cribado de YCM es una prueba clave en el abordaje diagnóstico de la infertilidad masculina. La obtención de un resultado genético adecuado permite elegir técnicas de reproducción asistida idóneas, prevenir tratamientos innecesarios y la transmisión de defectos genéticos a la descendencia. (AU)

Background and objective: The presence of microdeletions in the Y-chromosome azoospermia factor (AZF) region (YCMs) is considered the most frequent genetic cause of male infertility along with Klinefelter syndrome. The objective of this study was to investigate the frequencies and type of YCMs in infertile men in Aragon and to analyze the relationship between sex hormones, sperm count and microdeletions in them.Patients and methodsRetrospective descriptive study of 644 men who during 2006–2019 were screened for YCMs using YChromStrip (Operón, Spain) by PCR+reverse hybridization, spermiogram, karyotype and quantification of sex hormones.ResultsThe frequency of YCMs was 3.88% (25/644), not being detected in any patient with mild or normospermic oligozoospermia, that is, in sperm counts higher than 5×106/mL. The group of azoospermic patients was the one that presented a higher frequency of YCMs (14.58%, 14/96). Deletions in the AZFc region were the most frequent (68%). 20% (5/25) of patients with YCMs also presented some type of karyotype abnormality that included aneuploidies, deletions, duplications and/or translocations. Sperm count was significantly lower and FSH and LH concentrations significantly higher in the group of patients with YCMs.ConclusionsYCMs screening is a key test in the diagnostic approach to male infertility. Obtaining an adequate result allows choosing suitable assisted reproduction techniques, preventing unnecessary treatments and the transmission of genetic defects to offspring. (AU)

Bioprospecting of the probiotic potential of yeasts isolated from a wine environment.

Autochthonous yeasts of oenological origin are adapted to highly stressful and selective environments, which makes them potential candidates for probiotics. The objective of the present study was to explore the probiotic potential of 96 native yeasts of oenological origin, their biosafety, resistance to gastrointestinal tract conditions and adhesion properties. Regarding biosafety, 66 isolates shown negative hemolytic activity, negative urease activity and susceptibility to 3 or more antifungals. After the gastrointestinal resistance test, 15 isolates were selected that showed growth at different temperatures, tolerance to low pH and the presence of bile salts in in vitro tests. In general, survival after simulated conditions of the gastrointestinal tract was high and more restrictive was the duodenal. The results of the adhesion properties showed highly variable hydrophobicity and a high percentage of autoaggregation at 24 h. The maximum production of biofilm was detected in the Pichia strains. Of a total of 96 yeast strains, 15 non-Saccharomyces yeasts presented suitable properties as probiotic candidates. The native winemaking strains performed better than the reference probiotic strain, Saccharomyces cerevisiae var. boulardii CNCM I-745, which reaffirms that these strains are promising probiotic candidates and further studies are necessary to confirm their probiosis.

Ureteral Stenosis and Fistula after Kidney Transplantation.

INTRODUCTION: Ureteral complications after kidney transplantation are frequent and may have a negative impact on morbidity and graft function. Treatment modalities include conservative, endourological, and surgical techniques, with variable outcomes. The purpose of this study was to report the incidence, characteristics, treatment, and outcomes of ureteral complications at our center. METHODS: Retrospective study of kidney transplants performed at our unit between 2015 and 2020, analyzing incidence, characteristics, treatment, and outcomes of ureteral stenoses and fistulas. RESULTS: Of 648 kidney transplants, we present 3.24% stenosis and 2.16% ureteral fistulas, with a mean time from transplantation of 101.4 and 24.4 days, respectively. Primary treatment was open surgical repair in 52.4% stenosis and 100% fistulas, with a success rate of 90.9% and 71.4%, respectively. Anterograde balloon dilatations were performed in 33.3% of stenosis with 40% success. Three patients required surgery as a secondary approach with 100% success. Major complications (Clavien-Dindo III) were observed in 18.5% following surgical repair. After a mean follow-up of 31.1 ± 20.9 months, we observe 88.6% of functioning grafts. We found no significant differences in graft survival between patients with or without ureteral complications (p 0.948). CONCLUSION: Surgical repair of ureteral complications offers satisfactory results with low associated morbidity. Endourological techniques are less effective and should be reserved for selected cases. With adequate management, there is no impact on graft survival.

[AZF gene microdeletions in azoospermic-oligozoospermic males]. / Microdeleciones del gen AZF en varones azoospérmicos-oligozoospérmicos.

BACKGROUND AND OBJECTIVE: The presence of microdeletions in the Y-chromosome azoospermia factor (AZF) region (YCMs) is considered the most frequent genetic cause of male infertility along with Klinefelter syndrome. The objective of this study was to investigate the frequencies and type of YCMs in infertile men in Aragon and to analyze the relationship between sex hormones, sperm count and microdeletions in them. PATIENTS AND METHODS: Retrospective descriptive study of 644 men who during 2006-2019 were screened for YCMs using YChromStrip (Operón, Spain) by PCR+reverse hybridization, spermiogram, karyotype and quantification of sex hormones. RESULTS: The frequency of YCMs was 3.88% (25/644), not being detected in any patient with mild or normospermic oligozoospermia, that is, in sperm counts higher than 5×106/mL. The group of azoospermic patients was the one that presented a higher frequency of YCMs (14.58%, 14/96). Deletions in the AZFc region were the most frequent (68%). 20% (5/25) of patients with YCMs also presented some type of karyotype abnormality that included aneuploidies, deletions, duplications and/or translocations. Sperm count was significantly lower and FSH and LH concentrations significantly higher in the group of patients with YCMs. CONCLUSIONS: YCMs screening is a key test in the diagnostic approach to male infertility. Obtaining an adequate result allows choosing suitable assisted reproduction techniques, preventing unnecessary treatments and the transmission of genetic defects to offspring.