Adaptation to spindle assembly checkpoint inhibition through the selection of specific aneuploidies.

Both the presence of an abnormal complement of chromosomes (aneuploidy) and an increased frequency of chromosome missegregation (chromosomal instability) are hallmarks of cancer. Analyses of cancer genome data have identified certain aneuploidy patterns in tumors; however, the bases behind their selection are largely unexplored. By establishing time-resolved long-term adaptation protocols, we found that human cells adapt to persistent spindle assembly checkpoint (SAC) inhibition by acquiring specific chromosome arm gains and losses. Independently adapted populations converge on complex karyotypes, which over time are refined to contain ever smaller chromosomal changes. Of note, the frequencies of chromosome arm gains in adapted cells correlate with those detected in cancers, suggesting that our cellular adaptation approach recapitulates selective traits that dictate the selection of aneuploidies frequently observed across many cancer types. We further engineered specific aneuploidies to determine the genetic basis behind the observed karyotype patterns. These experiments demonstrated that the adapted and engineered aneuploid cell lines limit CIN by extending mitotic duration. Heterozygous deletions of key SAC and APC/C genes recapitulated the rescue phenotypes of the monosomic chromosomes. We conclude that aneuploidy-induced gene dosage imbalances of individual mitotic regulators are sufficient for altering mitotic timing to reduce CIN.

Adaptation to high rates of chromosomal instability and aneuploidy through multiple pathways in budding yeast.

Both an increased frequency of chromosome missegregation (chromosomal instability, CIN) and the presence of an abnormal complement of chromosomes (aneuploidy) are hallmarks of cancer. To better understand how cells are able to adapt to high levels of chromosomal instability, we previously examined yeast cells that were deleted of the gene BIR1, a member of the chromosomal passenger complex (CPC). We found bir1Δ cells quickly adapted by acquiring specific combinations of beneficial aneuploidies. In this study, we monitored these yeast strains for longer periods of time to determine how cells adapt to high levels of both CIN and aneuploidy in the long term. We identify suppressor mutations that mitigate the chromosome missegregation phenotype. The mutated proteins fall into four main categories: outer kinetochore subunits, the SCFCdc4 ubiquitin ligase complex, the mitotic kinase Mps1, and the CPC itself. The identified suppressor mutations functioned by reducing chromosomal instability rather than alleviating the negative effects of aneuploidy. Following the accumulation of suppressor point mutations, the number of beneficial aneuploidies decreased. These experiments demonstrate a time line of adaptation to high rates of CIN.

Vivax malaria in a blood donor in Spain, relapse or a new infection in a malaria non-endemic country?

Malaria is a vectorborne disease caused by protozoan of the genus Plasmodium, which can also be transmitted by the transfusion of infected red blood cells. One year after return from a travel to Honduras, a Spanish traveller developed vivax malaria. Prior to the onset of symptoms, the donor made a donation that tested non-reactive using an immunological test for malaria. Samples from the donor taken before donation and tested by serological and molecular methods were negative but positive at the time of hospital admission. The possible sources of the donors' infection, imported versus locally acquired, are discussed.

Damping-Off and Root Rot of Pepper Caused by Fusarium oxysporum in Almería Province, Spain.

Bell pepper (Capsicum annuum L.) is intensively cropped in ~9,920 ha of plastic houses in southern Spain. In summer 2013, pepper seedlings cv. Melchor, Acorde, Galena, Prometeo, and Souleria, with 4 to 8 leaves, grown in a nursery greenhouse near El Ejido, Almería Province, exhibited root rot and stunting. Incidence of symptomatic plants was ~35% among over 10 million. Fusarium sp. was consistently isolated on potato dextrose agar (PDA) from primary and secondary roots of symptomatic plants. Eight single spore isolates (FC1, FC2, FC3, FC4, FC5, FC6, FC11, and FC12) were identified on PDA, carnation leaf-piece agar medium, and Spezieller Nährstoffarmer agar medium as Fusarium oxysporum because of their production of macroconidia (20.5 to 38.2 × 3.9 to 5.8 µm) containing mostly three or rarely four septa, with foot-shaped basal cells. Microconidia (5.9 to 16.5 × 2.6 to 4.7 µm) with 0 to 1 septa formed on false heads on short monophialides and chlamydospores. DNA was extracted from various isolates used in the pathogenicity test, and a portion of the elongation translation factor 1-alpha using primers EF-1 and EF-2 was amplified and sequenced. All the pathogenic isolates were identical, and they differed from the non-pathogenic in 6 to 8 base pairs. The isolates had 99% homology with several isolates of F. oxysporum corresponding to different specialized forms (vasinfectum, lilii, lycopersici, and radicis-lycopersici) at the Fusarium-ID database (1) and GenBank. The sequences of two isolates, FC-6 and FC-12, were deposited in GenBank with accession nos. KF928930 and KF928931, respectively. The pathogenicity of these eight isolates was tested on pepper cv. Melchor in 1-liter containers filled with vermiculite in August and October. Seedlings were inoculated at sowing. PDA plates fully covered with the colony of each isolate were separately blended and homogenized with 300 ml of sterile distilled water. Inocula (5.0 × 105 to 9.4 × 106 conidia/ml) were poured at 50 ml per container. Each experiment had four replicates and 5 to 6 plants per replicate. Treatments with different isolates were arranged in a randomized complete block design. In both experiments, the same number of uninoculated seedlings served as controls. The plants were maintained for 40 days following inoculation in a greenhouse with mean temperatures of 24.0 to 32.4°C and 23.6 to 31.20°C for August and October experiments, respectively. In both experiments, all control plants and those inoculated with FC2, FC3, and FC4 remained asymptomatic. The first wilting occurred 11 days after inoculation. At the end of the August experiment, plants inoculated respectively with FC1, FC5, FC6, FC11, and FC12 showed symptoms in 60, 70, 65, 80, and 90% and 25, 0, 15, 40, and 25% died. At the October experiment, plants showed symptoms in 91.7, 95.8, 100.0, 91.7, and 87.5% and 83.3, 75, 62.5, 83.3, and 79.2% died. Symptomatic plants exhibited damping-off, necrosis of the primary and secondary roots, and sometimes necrotic streaks on the stem. F. oxysporum was consistently recovered from the primary root of symptomatic plants in both experiments and 10 of these isolates were inoculated in a third pathogenicity test, being all pathogens, thus fulfilling Koch's postulates. Although F. oxysporum was reported in peppers (2), to our knowledge, this is the first report of F. oxysporum as the causal agent of damping-off and root rot in pepper seedlings in Almería Province. References: (1) D. M. Geiser et al. Eur. J. Plant Pathol. 110:473, 2004. (2) K. Pernezny et al. Compendium of Pepper Diseases. APS Press, St. Paul, MN, 2009.

Clinical Usefulness of Prostate-specific Membrane Antigen-ligand Positron Emission Tomography/Computed Tomography for the Detection of Prostate Cancer Biochemical Recurrence after Primary Radiation Therapy in Patients with Prostate-specific Antigen Below the Phoenix Threshold: Systematic Review and Meta-analysis.

AIMS: After primary radiotherapy, biochemical recurrence is defined according to the Phoenix criteria as a prostate-specific antigen (PSA) value >2 ng/ml relative to the nadir. Several studies have shown that prostate-specific membrane antigen (PSMA)-ligand positron emission tomography/computed tomography (PET/CT) can help in detecting recurrence in patients with low PSA values. This study aimed to assess the detection rate and patterns of PSMA-ligand PET/CT uptake in patients with suspected biochemical recurrence after primary radiotherapy and with PSA levels below the Phoenix threshold. MATERIALS AND METHODS: The meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Articles providing data on patients with suspected prostate cancer recurrence after primary radiotherapy with a PSA value below the Phoenix threshold and who underwent PSMA-ligand PET/CT were included. Quality assessment was carried out using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). RESULTS: In total, five studies were included, recruiting 909 patients (202 with PSA ≤2 ng/ml). The PSMA-ligand detection rate in the patients with ≤2 ng/ml ranged from 66 to 83%. The most frequent source of PSMA-ligand PET/CT uptake was local recurrence, followed by lymph node metastasis and bone metastasis. PSMA-ligand PET/CT uptake due to local-only recurrence was more likely in patients with PSA ≤2 ng/ml compared with PSA > 2 ng/ml: risk ratio 0.72 (95% confidence interval 0.58-0.89), P = 0.003. No significant differences were observed in the detection of PSMA-ligand uptake in other areas. Limitations include a lack of biopsy confirmation, cohort reports with small sample sizes and a potentially high risk of bias. CONCLUSION: A significant detection of PSMA-ligand-avid disease was observed in patients with PSA levels below the Phoenix threshold. There was a higher likelihood of detecting local-only uptake when the PSA value was ≤2 ng/ml. The findings suggest that a critical review of the Phoenix criteria may be warranted in the era of PSMA-ligand PET/CT and highlight the need for further prospective trials.

Laparoscopic transperitoneal radical prostatectomy in renal transplant recipients: a review of the literature.

OBJECTIVES: To report our experience with laparoscopic radical prostatectomy (LRP) for the treatment of localized prostate carcinoma in two renal transplant recipients and a review of the literature. PATIENTS AND METHODS: We retrospectively identified all patients who had undergone LRP for clinically localized prostate cancer between 2002 and 2008 at our institution (n = 1150). Of these patients, two were renal transplant recipients (one with donor renal transplant cadaver and the other with prior transplantectomy). We reviewed all available clinicopathological data and the scientific literature. RESULTS: The two patients underwent successful LRP with no major complications. The mean (range) operative time was 200 (180-220) min with a mean estimated blood loss of 300 (200-400) mL. There were no changes in renal graft function as measured by serum creatinine level. At pathology, the surgical margins were negative and disease was organ-confined in each case. The two patients tolerated the procedure well and had a mean (range) hospital stay of 3.5 (3-4) days. CONCLUSIONS: The data from our two patients suggest that LRP, as an accepted minimally invasive treatment for a middle-aged man with organ-confined prostate cancer, is a technically feasible and safe treatment of localized prostate cancer in renal transplant recipients.

[Laparoscopic radical nephrectomy in big surgical specimens]. / Nefrectomía radical laparoscópica en piezas quirúrgicas de gran tamaño.

INTRODUCTION: The retroperitoneal surgery is the clearer indication for the laparoscopic approach. Still there are indications for open surgery because of the complexity of the patient and the surgeon experience. OBJECTIVES: The main objective is to report our experience of laparoscopic radical nephrectomies in patient with tumors greater than 7 cm. or surgical specimens with more than 700 g of weight. We analyze their characteristics, complications rate, surgical time, postoperative outcome and hospital stay. MATERIALS AND METHODS: Since July 2004 to July 2008 we have performed 104 laparoscopic radical nephrectomies. We have selected 41 patients with characteristics of big surgical specimens. RESULTS: The average surgical time has been of 184,3 min. Only 1 case has been converted into open surgery and only 1 intraoperative death because of cardiologic arrhythmia. The average hospital stay has been of 3,51 days. The complications rate and postoperative outcome are similar to the whole series. DISCUSSION: Laparoscopic nephrectomy is technically less complex than radical prostatectomy. However, their possible complication implies a much bigger severity. The more complex cases must be approach laparoscopically only after a wide experience. Actually, in our department we usually indicate an open approach when surgical specimen crossover the abdominal middle line and in those cases where the tumoral thrombus affect the main renal vein and/or the vena cava.

Laparoscopic donor nephrectomy versus open donor nephrectomy: Outcomes from a single transplant center. / Nefrectomía laparoscópica del donante vivo en comparación con nefrectomía abierta del donante vivo.

OBJECTIVES: Laparoscopic donor nephrectomy (LDN) is currently replacing open donor nephrectomy (ODN) across the world. Its advantages in terms of patient recovery are well known. We sought to compare surgical outcomes, particularly renal function during the post-nephrectomy period, for renal grafts procured by LDN versus ODN in our center. METHODS: We retrospectively analyzed all cases of living donor nephrectomies performed from 2004 to 2014 at Hospital Universitario La Paz. We compared demographic data; medical background, operative times, post-operative complications, and renal function follow up at 6, 12 and 18-month controls. RESULTS: A total of 114 living donor nephrectomies were performed: 85 LDN and 29 ODN. Demographic characteristics and medical background were similar among both groups, except mean donor age; 41.4 vs 47.4 years (p = 0.009) in the LDN and ODN groups respectively. LDN was used predominantly for left kidneys (83 out of 85), and ODN for right kidneys (28 out of 29). Although not significantly, mean operative time was shorter for the LDN group (169.37 vs 181.46 minutes; p = 0.2). Mean warm ischemia time was shorter for the ODN group (2.92 vs 2.36 minutes; p = 0.28). Differences between post-operative complications were not statistically different between both groups (p = 0.19). There were no conversions from LDN to ODN, and no re-admissions were registered. Length of stay was slightly shorter in LDN but not different (4.29 vs 4.92 days; p = 0.43). Renal function follow-up, measured with serum creatinine levels showed no difference over time (p = 0.67). CONCLUSIONS: Data from our series demonstrate that outcomes and renal function follow up over time were similar among both groups. In expert hands, this altruistic procedure can be performed with a minimally invasive approach without an increased complication rate or compromising renal function in donors.

OBJETIVOS: La nefrectomía laparoscópica del donante vivo (NLDV) está reemplazando actualmente a la nefrectomía abierta (NADV) en todo el mundo. Sus ventajas en términos de recuperación del paciente son bien conocidas. Comparamos los resultados quirúrgicos, particularmente función renal durante el periodo postnefrectomía, para los injertos obtenidos en nuestro centro por NLDV o NADV. MÉTODOS: Analizamos retrospectivamente todos los casos de nefrectomía del donante vivo realizados entre 2004 y 2014 en el Hospital Universitario La Paz. Comparamos los datos demográficos, antecedentes médicos, tiempo operatorio, complicaciones postoperatorias y funcion renal a los 6, 12 y 18 meses de seguimiento. RESULTADOS: Se han realizado un total de 114 nefrectomías del donante vivo: 85 NLDV y 29 NADV. Las características demográficas y antecedentes médicos eran similares entre ambos grupos, excepto la edad media del donante: 41,4 vs 47,4 años (p = 0,009) en los grupos de NLDV y NADV, respectivamente. La NLDV se utilizó preferentemente para riñones izquierdos (83 de 85) y la NADV para los riñones derechos (28 de 29). Aunque no fue significativo, el tiempo medio de operación del grupo de NLDV fue menor que el de NADV (169,37 vs 181,46 minutos; p = 0,2). El tiempo medio de isquemia caliente era menor en el grupo de NADV (2,92 vs 2,36 minutos; p = 0,28). No hubo diferencias estadísticamente significativas en las complicaciones postoperatorias entre ambos grupos (p=0,19). No hubo conversión a cirugía abierta en ninguna NLDV y no se registró ningún reingreso. La estancia hospitalaria fue ligeramente menor en la NLDV pero la diferencia no fue estadísticamente significativa (4,29 vs 4,92 días; p = 0,43). La función renal en el seguimiento, medida con los niveles de creatinina sérica no mostró diferencias con el tiempo (p = 0,67). CONCLUSIONES: Los datos de nuestra serie demuestran que los resultados y función renal en el seguimiento eran similares entre ambos grupos. En manos expertas, este procedimiento altruista puede ser realizado con un abordaje mínimamente invasivo sin aumento de la tasa de complicaciones o compromiso de la función renal del donante.

Impact of a clinical pathway in patient care following surgery on laparoscopic radical prostatectomy.

PURPOSE: The aim of this study was to evaluate the impact of clinical pathway (CP) implementation in laparoscopic radical prostatectomy (LRP) has had on patient care and clinical evolution after discharge. MATERIALS AND METHODS: Eighty-six patients were included in 2 groups: first group was composed of patients operated since the new technique (LRP) was used until the CP was implemented (26 patients operated in 2002) and, second group, with 60 patients, followed the CP during 2004 and 2005. RESULTS: The operative time was reduced from 377.7 to 172.3 minutes after the CP implementation. The duration of bladder catheterization decreased by more than 10 days (from 26.17 to 15.85 days) and that of thromboprophylaxis was reduced from 6.44 to 3.38 days. No difference was found in the rate of complications in the first month after surgery, nor was there any difference in the rate of occurrence of erectile dysfunction, incontinence, and biochemical recurrence during the first year after surgery. CONCLUSION: After the implementation of the CP, there have been better results in patient care, such as reduction in the duration of catheterization and thromboprophylaxis. In comparison with other studies, we observed a clear reduction in length of stay and operative time. However, there is still room for improvement in reducing the duration of catheterization.

[Laparoscopic urinary diversions]. / Derivaciones urinarias laparoscópicas.

INTRODUCTION: The treatment of the invasive bladder cancer and the recurrent T1G3 is clearly established in radical cystectomy and pelvic linphadenectomy. One of the fields where the laparoscopic approach implies more doubts is the treatment of bladder cancer, because it requires experience enough in pelvic laparoscopic surgery and the urinary diversion implies great technical difficulties to the laparoscopic approach. OBJECTIVES: The main goal of this article is to report our results with the urinary diversion after laparoscopic radical cystectomy where the ureteral anastomosis has been performed by a laparoscopic approach. METHODS: From January 2005 to December 2007 we have performed 67 laparoscopic radical cistectomies. We conducted 28 laparoscopic urinary diversions with our technique: 7 neobladder with an average age of 54, 85 years and 21 ileal conduit with an average age of 69, 15 years. RESULTS: The averagesurgical time for enterocistoplasty with laparoscopic urethral and ureteral anastomosis is of 5 hours and 30 minutes. For the cutaneous ureteroileostomy with laparoscopic ureteral anastomosis the average surgical time has been of 4 hours and 30 minutes. We have had 1 case of urinary leakage in the laparoscopic neobladder and 3 cases in the laparoscopic ileal conduit (14%). We have not intestinal dehiscence nor ileal-ureteric stenosis. The average hospital stay for laparoscopic neobladder is for the 85% of cases of 13.6 days, and of 11.8 days for the 77.7% of ileal ureteric laparoscopies. DISCUSSION: The laparoscopic radical cystectomy is still a procedure reserved for groups with great experience in laparoscopic surgery. Nowadays, the most accepted procedure by most groups includes perform the cystectomy by a laparoscopic approach and the urinary diversion by an open approach. There is no evidence of the advantages of laparoscopic urinary diversion. It is necessary to perform comparative studies to clearly define the role of laparoscopic surgery in the urinary diversion.

[Leukemic infiltration of the urinary bladder. A new case and literature review]. / Infiltración vesical por leucemia linfoblástica aguda. A propósito de un caso y revisión de la literatura.

We expose you one case of leukemic infiltration of the urinary bladder. This kind of infiltration is rare so we reviewed the literature finding 14 cases since 1932. Although this hematological infiltration is very unusual, it should be considered in patients with leukemia and hematuria.

Care in patients with epidermal necrolysis in burn units. A nursing perspective.

OBJECTIVE: To describe how nursing care is delivered to patients with epidermal necrolysis in burn units/specialized units in Spain and a selection of countries. METHOD: Descriptive cross-sectional study. Data were collected through a structured questionnaire which was sent to nurse managers in all burn units in Spain and a selection of countries. Descriptive statistics was used to summarize the results. RESULTS: All BU/SUs in Spain (n=12) and seven BU/SUs from a selection of countries completed the questionnaire. A lack of specific nursing protocols on Epidermal Necrolysis was observed in most burn units in Spain. Skin cleansing techniques such as showering were only reported by participants from Spain. Use of antiseptics was less frequent in other countries. Conservative skin management was the most extended practice reported by all participants. The use of vaginal molds to prevent synechiae and coverage of the ocular surface with amniotic membrane to minimize sequelae were rarely reported. Pain assessment was not always documented in sedated patients and few participants reported the use of specific scales for this purpose. All nurses agreed in the need for consensus nursing care guidelines on the disease. CONCLUSIONS: Nursing care in patients with epidermal necrolysis varied between burn units in Spain. Differences and similarities were observed when compared with burn units in other countries. Genital and ocular care were outdated in all BU/SUs. Pain assessment documentation was suboptimal. Evidence-based nursing care guidelines were generally demanded by all participants to help reduce mortality and morbidity of this rare and often devastating disease.

[Laparoscopic nephron sparing surgery. Initial experience]. / Cirugía renal laparoscópica conservadora de parénquima. Experiencia inicial.

We present our initial experience in laparoscopic nephron sparing surgery. It's a technically advanced procedure requiring considerable minimally invasive expertise. This technique is particularly attractive compared to an open conventional procedure with its larger incision and associated morbidity.

Discapacidad intelectual y medidas adoptadas durante la pandemia de COVID-19: efectos comportamentales / Intellectual disability and adopted measures during the COVID-19 pandemic: behavioral effects

Actualmente, y en el contexto del estadode emergencia sanitaria, se han implantadouna serie de medidas de prevención y contenciónaplicables a toda la población. Enparticular, los centros sociosanitarios hantenido que adaptarse, diseñando medidasespeciales y aplicando planes de contingencia,que han provocado modificaciones en elentorno habitual de los residentes. Con elfin de observar los efectos de la pandemiasobre la conducta de personas con discapacidadintelectual residentes en un centrosociosanitario, se aplicó el Inventario parala Planificación de Servicios y ProgramaciónIndividual (ICAP). Los resultados, comparadoscon evaluaciones previas a la pandemiapor COVID-19, mostraron que el funcionamientoadaptativo era similar al anterior aeste periodo, pero existía un déficit en destrezasmotoras y en las destrezas de la vidaen comunidad. Así mismo, las alteracionesdel comportamiento habían aumentado, tantoen la puntuación general como en cadauno de sus índices específicos. Además, seencontró una relación inversa entre la edady la conducta adaptativa y una correlación positiva entre la edad y las alteraciones de la conducta. (AU)

Currently, and due to the existing healthemergency context, prevention and containmentmeasures applicable to the entirepopulation have been implemented. In particular,social and health centers have hadto adapt, designing a package of specialmeasures and applying guidelines and contingencyplans that have caused changes inthe habitual environment of the residents.In order to observe the effects of the pandemicon people with intellectual disabilitiesin social health centers, the Inventoryfor Client and Agency Planning (ICAP) wasapplied. The results, compared to previousevaluation, showed that adaptive functioningwas similar to that before this period,but there was a decrease in motor and socialskills. Furthermore, behavioral problems hadincreased, in the general index and in each of its specific index. In addition, an inverse relationship was found between age and adaptive behavior and a positive correlation between age and behavior disorders. (AU)

Instrucciones previas: breve guía para un ejercicio de autonomía / Advance instructions: short guide to an exercise of autonomy

Las instrucciones previas, también denominadas decisiones o voluntades anticipadas,o testamento vital, constituyen una manifestación de la voluntad de los pacientes y, por tanto, son expresión de la autonomía de la persona. Se definen como el proceso en el que una persona planifica los cuidados sanitarios y la asistencia que desea recibir en el futuro, en el momento en que no sea capaz de tomar decisiones por sí misma.La planificación anticipada de cuidados y decisiones (PACD), que incluye elaborar esos documentos de voluntades anticipadas, es un modo de relación asistencial sobre la que todavía hay poca experiencia en nuestro país.La PACD se define como un "proceso voluntario de comunicación y deliberación entre una persona capaz y profesionales implicados en su atención, acerca de los valores, deseosy preferencias que quiere que se tengan encuenta en la atención sanitaria que recibirácomo paciente, fundamentalmente en losmomentos finales de la vida" (1).El objetivo es que la persona, junto conlos profesionales, delibere y establezca cómoquiere ser tratada durante el proceso terapéutico.Incluye los valores relevantes delpaciente, las preferencias sanitarias de caráctergeneral, las indicaciones sanitariasconcretas (rechazo o solicitud de intervenciones,donación de órganos...), expresiónde sentimientos hacia otros ("lo siento","gracias", "te perdono", etc), y/o designarun representante.A través del documento de instruccionesprevias que confirma que se ha dado el procesode reflexión, comunicación y descripciónde esas voluntades anticipadas, las personaspueden decidir acerca de los tratamientos ycuidados de salud que desean o no recibircuando se encuentren en una circunstanciaen la que no puedan manifestar su voluntadpersonalmente.Su fundamento ético es:Respetar y promover la autonomía del paciente.Asegurar que se valoren las situaciones decompetencias limitadas o inexistentes. (AU)

Advance instructions, also called decisionsor advance directives, or living wills,constitute a manifestation of the will of the patients and, therefore, are an expression of the autonomy of the person. They are defined as the process in which a person plans the health care and assistance they want to receive in the future, at the time when they are not able to make decisions for themselves. Advance Care Planning and Decisions(ACPD) which includes developing these advance directives documents. It is something that the law does not collect but does not prevent, and there is very little experience and research on it. They define it as a "voluntary process of communication and deliberation between a capable person and professionals involved in their care, about the values, desires and preferences that they want to betaken into account in the health care thatthey will receive as a patient, fundamentallyin the moments end of life" (1).The objective is for the person, togetherwith the professionals, to establish how theywant to be treated during the therapeuticprocess. It includes the relevant values ofthe patient, general health preferences, specifichealth indications (refusal or requestfor interventions, organ donation ...), expressionof feelings towards others ("I'm sorry","thank you", "I forgive you", etc), and/or appoint a representative.Through the advance directive documentthat confirms that the process of reflection,communication and description of these advancedirectives has been given, people candecide about the treatments and health carethey want or not to receive when they are ina circumstance in the one that cannot expresstheir will personally.Its ethical foundation is:Respect and promote the autonomy of thepatient.Preserve that value in situations of limited or nonexistent skills. (AU)

Renal colic during pregnancy: Diagnostic and therapeutic aspects. Literature review.

INTRODUCTION: Renal colic during pregnancy is a rare urgency but is one of the most common non-obstetric reasons for hospital admission. The management often means a challenge for the urologist and gynecologist due to the complexity involved in preserving the maternal and fetal well-being. MATERIAL AND METHODS: We performed a literature search within the PubMed database. We found 65 related articles in English. We selected 36 for this review prioritizing publications in the last two decades. RESULTS: The anatomical and functional changes of the genitourinary system during pregnancy are well documented; also during pregnancy, there are several metabolic pro-lithogenic factors. The most common clinical presentation is flank pain accompanied by micro or macro hematuria. US provides data identifying renal obstruction shown by an increased renal resistance index. MRI allows differentiating the physiological dilatation from the pathological caused by an obstructive stone showing peripheral renal edema and renal enlargement. Low dose CT has been determined to be a safe and highly accurate imaging technique. Once the diagnosis is confirmed, the initial management of patients should be conservative. When conservative management fails the interventional treatment is mandatory, a urinary diversion of the obstructed renal unit either by a JJ stent or through a PCN catheter has to be done. The definitive management of the stone can be done in the postpartum or deferred ureteroscopy can be considered during pregnancy. CONCLUSIONS: Renal colic during pregnancy is an uncommon urgency, so it is important for the urologist to know the management of this condition.

A novel heterozygous mutation in the Birt-Hogg-Dubé Syndrome.

OBJETIVE: Our aim is to present a novel mutation of the Birt-Hogg-Dubé Syndrome. METHODS: We present a case report of a 70-year-old male with three solid nodulary lesions of 4, 2.6, and 3 cm each in the right kidney, and two lesions of 1.5 and 1.3 cm in the left kidney. RESULTS: Needle biopsy was performed. The pathological analysis of right kidney lesions revealed a renal tumor suggestive of chromophobe renal cell carcinoma and medullar tumor with zones that suggested oncocytosis. Genetic test results were positive for a novel heterozygous mutation c.1198G>A; p.V400I in exon 11 of the FLCN gene. CONCLUSION: In patients presenting with bilateral multifocal renal tumors of oncocytic hybrid histology, Birt- Hogg-Dubé syndrome should be the first diagnosis in mind. The mutation found in this patient has not been previously described in the literature in the context of BHD.

Recruitment dynamics of ESCRT-III and Vps4 to endosomes and implications for reverse membrane budding.

The ESCRT machinery mediates reverse membrane scission. By quantitative fluorescence lattice light-sheet microscopy, we have shown that ESCRT-III subunits polymerize rapidly on yeast endosomes, together with the recruitment of at least two Vps4 hexamers. During their 3-45 s lifetimes, the ESCRT-III assemblies accumulated 75-200 Snf7 and 15-50 Vps24 molecules. Productive budding events required at least two additional Vps4 hexamers. Membrane budding was associated with continuous, stochastic exchange of Vps4 and ESCRT-III components, rather than steady growth of fixed assemblies, and depended on Vps4 ATPase activity. An all-or-none step led to final release of ESCRT-III and Vps4. Tomographic electron microscopy demonstrated that acute disruption of Vps4 recruitment stalled membrane budding. We propose a model in which multiple Vps4 hexamers (four or more) draw together several ESCRT-III filaments. This process induces cargo crowding and inward membrane buckling, followed by constriction of the nascent bud neck and ultimately ILV generation by vesicle fission.

Human native Cav1 channels in chromaffin cells: contribution to exocytosis and firing of spontaneous action potentials.

The present study was performed to evaluate the Cav1 channel subtypes expressed in human chromaffin cells and the role that these channels play in exocytosis and cell excitability. Here we show that human chromaffin cells obtained from organ donors express Cav1.2 and Cav1.3 subtypes using molecular and pharmacological techniques. Immunocytochemical data demonstrated the presence of Cav1.2 and Cav1.3 subtypes, but not Cav1.1 or Cav1.4. Electrophysiological experiments were conducted to investigate the contribution of Cav1 channels to the exocytotic process and cell excitability. Cav1 channels contribute to the exocytosis of secretory vesicles, evidenced by the block of 3µM nifedipine (36.5±2%) of membrane capacitance increment elicited by 200ms depolarizing pulses. These channels show a minor contribution to the initiation of spontaneous action potential firing, as shown by the 2.5 pA of current at the threshold potential (-34mV), which elicits 10.4mV of potential increment. In addition, we found that only 8% of human chromaffin cells exhibit spontaneous action potentials. These data offer novel information regarding human chromaffin cells and the role of human native Cav1 channels in exocytosis and cell excitability.

[Open and laparoscopic adrenalectomy. 10 years review]. / Suprarrenalectomía abierta y laparoscópica. Revisión de 10 años.

We present a 10 years open adrenalectomy review in our Service and the beginning of laparoscopic adrenalectomy in the last year as a part of the retroperitoneal laparoscopic program at the Hospital Universitario La Paz . The first laparoscopic adrenalectomy was done after 21 retroperitoneal laparoscopic surgeries. Our initial experience has been so good that we have reduced the contraindications for this technique and we have increased the number of laparoscopic surgery cases.