Six Decades of Hindsight Into Yesa Reservoir (Central Spanish Pyrenees): River Flow Dwindles as Vegetation Cover Increases and Mediterranean Atmospheric Dynamics Take Control.

River discharge has experienced diverse changes in the last decades due to modification of hydrological patterns, anthropogenic intervention, re-vegetation or annual and interannual climatic and atmospheric fluctuations. Assessing the recent changes in river discharge and understanding the main drivers of these changes is thus extremely important from theoretical and applied points of view. More specifically, here we want to draw attention toward the impacts of streamflow changes on reservoir storage and operation. We describe the hydrological dynamics of the Yesa reservoir draining catchment, located in the central Spanish Pyrenees, and characterize the reservoir operation modes over the last 60 years (1956-2020). We analyze concurrent climatic (precipitation, air temperature, drought index), atmospheric mechanisms, land cover (Normalized Different Vegetation Index) and discharge (inlet and outlet of Yesa reservoir) time-series. By using the wavelet transform methodology, we detect historical breakpoints in the hydrological dynamics at different time-scales. Distinctive periods are thus identified. More regular seasonal flows characterized the catchment's dynamics during the first decades of the study period, while the last decades were characterized by a high inter-annual variability. These changes are primarily attributed to the natural re-vegetation process that the catchment experienced. Furthermore, we related changes in atmospheric circulation with a decline of the long-term discharge temporal features. This research contributes to the understanding of long-term river discharge changes and helps to improve the reservoir management practices.

The potential of using climate indices as powerful tools to explain mortality anomalies: An application to mainland Spain.

Changes in the frequency and magnitude of extreme weather events represent one of the key indicators of climate change and variability. These events can have an important impact on mortality rates, especially in the ageing population. This study assessed the spatial and seasonal distributions of mortality rates in mainland Spain and their association with climatic conditions over the period 1979-2016. The analysis was done on a seasonal and annual basis using 79 climatic indices and regional natural deaths data. Results indicate large spatial variability of natural deaths, which is mostly related to how the share of the elderly in the population varied across the studied regions. Spatially, both the highest mortality rates and the largest percentage of elders were found in the northwest areas of the study domain, where an extreme climate prevails, with very cold winters and hot summers. A strong seasonality effect was observed, winter shows more than 10% of natural deaths compared to the rest of the seasons. Also, results suggest a strong relation between climatic indices and natural deaths, albeit with a high spatial and seasonal variability. Climatic indices and natural deaths show a stronger correlation in winter and summer than in spring and autumn.

Growth hormone-releasing hormone is produced by adipocytes and regulates lipolysis through growth hormone receptor.

BACKGROUND: Growth hormone-releasing hormone (GHRH) has a crucial role in growth hormone (GH) secretion, but little is known about its production by adipocytes and its involvement in adipocyte metabolism. OBJECTIVES: To determine whether GHRH and its receptor (GHRH-R) are present in human adipocytes and to study their levels in obesity. Also, to analyze the effects of GHRH on human adipocyte differentiation and lipolysis. METHODS: GHRH/GHRH-R and GH/GH-R mRNA expression levels were analyzed in human mature adipocytes from non-obese and morbidly obese subjects. Human mesenchymal stem cells (HMSC) were differentiated to adipocytes with GHRH (10-14-10-8 M). Adipocyte differentiation, lipolysis and gene expression were measured and the effect of GH-R silencing was determined. RESULTS: Mature adipocytes from morbidly obese subjects showed a higher expression of GHRH and GH-R, and a lower expression of GHRH-R and GH than non-obese subjects (P<0.05). A total of 10-14-10-10 M GHRH induced an inhibition of lipid accumulation and PPAR-γ expression (P<0.05), and an increase in glycerol release and HSL expression (P<0.05) in human differentiated adipocytes. A total of 10-12-10-8 M GHRH decreased GHRH-R expression in human differentiated adipocytes (P<0.05). A total of 10-10-10-8 M GHRH increased GH and GH-R expression in human differentiated adipocytes (P<0.05). The effects of GHRH at 10-10 M on adipocyte differentiation and lipolysis were blocked when GH-R expression was silenced. CONCLUSIONS: GHRH and GHRH-R are expressed in human adipocytes and are negatively associated. GHRH at low doses may exert an anti-obesity effect by inhibiting HMSC differentiation in adipocytes and by increasing adipocyte lipolysis in an autocrine or paracrine pathway. These effects are mediated by GH and GH-R.

Factors affecting carriage and intensity of infection of Calodium hepaticum within Norway rats (Rattus norvegicus) from an urban slum environment in Salvador, Brazil.

Urban slum environments in the tropics are conducive to the proliferation and the spread of rodent-borne zoonotic pathogens to humans. Calodium hepaticum (Brancroft, 1893) is a zoonotic nematode known to infect a variety of mammalian hosts, including humans. Norway rats (Rattus norvegicus) are considered the most important mammalian host of C. hepaticum and are therefore a potentially useful species to inform estimates of the risk to humans living in urban slum environments. There is a lack of studies systematically evaluating the role of demographic and environmental factors that influence both carriage and intensity of infection of C. hepaticum in rodents from urban slum areas within tropical regions. Carriage and the intensity of infection of C. hepaticum were studied in 402 Norway rats over a 2-year period in an urban slum in Salvador, Brazil. Overall, prevalence in Norway rats was 83% (337/402). Independent risk factors for C. hepaticum carriage in R. norvegicus were age and valley of capture. Of those infected the proportion with gross liver involvement (i.e. >75% of the liver affected, a proxy for a high level intensity of infection), was low (8%, 26/337). Sixty soil samples were collected from ten locations to estimate levels of environmental contamination and provide information on the potential risk to humans of contracting C. hepaticum from the environment. Sixty percent (6/10) of the sites were contaminated with C. hepaticum. High carriage levels of C. hepaticum within Norway rats and sub-standard living conditions within slum areas may increase the risk to humans of exposure to the infective eggs of C. hepaticum. This study supports the need for further studies to assess whether humans are becoming infected within this community and whether C. hepaticum is posing a significant risk to human health.

Accuracy of magnetic resonance enterography in the preoperative assessment of patients with Crohn's disease of the small bowel.

AIM: To assess the accuracy of magnetic resonance enterography in predicting the extension, location and characteristics of the small bowel segments affected by Crohn's disease. METHOD: This is a prospective study including a consecutive series of 38 patients with Crohn's disease of the small bowel who underwent surgery at a specialized colorectal unit of a tertiary hospital. Preoperative magnetic resonance enterography was performed in all patients, following a homogeneous protocol, within the 3 months prior to surgery. A thorough exploration of the small bowel was performed during the surgical procedure; calibration spheres were used according to the discretion of the surgeon. The accuracy of magnetic resonance enterography in detecting areas affected by Crohn's disease in the small bowel was assessed. The findings of magnetic resonance enterography were compared with surgical and pathological findings. RESULTS: Thirty-eight patients with 81 lesions were included in the study. During surgery, 12 lesions (14.8%) that were not described on magnetic resonance enterography were found. Seven of these were detected exclusively by the use of calibration spheres, passing unnoticed at surgical exploration. Magnetic resonance enterography had 90% accuracy in detecting the location of the stenosis (75.0% sensitivity, 95.7% specificity). Magnetic resonance enterography did not precisely diagnose the presence of an inflammatory phlegmon (accuracy 46.2%), but it was more accurate in detecting abscesses or fistulas (accuracy 89.9% and 98.6%, respectively). CONCLUSION: Magnetic resonance enterography is a useful tool in the preoperative assessment of patients with Crohn's disease. However, a thorough intra-operative exploration of the entire small bowel is still necessary.

Alopecia areata totalis and universalis: a multicenter review of 132 patients in Spain.

BACKGROUND: Alopecia areata totalis (AAT) and universalis (AAU) pose a therapeutic challenge. OBJECTIVE: To describe the clinical and epidemiological features, therapeutic response and prognostic factors in a large series of patients diagnosed with AAT and AAU. METHODS: This retrospective multicenter study included patients diagnosed with AAT/AAU with a minimum follow-up of 12 months. Response was assessed based on the regrowth of scalp hair. RESULTS: In all, 132 patients (92 women and 40 men) - 80 (61%) diagnosed with AAU and 52 (39%) diagnosed with AAT - were included. The median time between the presentation of alopecia areata (AA) and the development of extensive AA was 1 year and it was less than 4 years in 121 patients (91%). There was an initial response to treatment in 64% of patients, although only 14% presented a persistent response. Adverse side effects from the medications used were detected in 33% of patients. The prognostic factors associated with poor response were the presence of AAU and a positive family history of AA. CONCLUSIONS: Treatment of AAT and AAU is challenging. Although an initial regrowth may be achieved, the duration of response is usually short. There were no significant differences on the effectiveness or duration of response between the various systemic therapies.

Use of a linear stapler for the treatment of ileocolic fistula in Crohn's disease.

AIM: The study reports an easy technique for surgical management of some forms of ileocolic fistula in Crohn's disease. METHOD: Five patients with Crohn's disease with ileocolic fistula (2011-2014) have been managed by the application of linear stapler devices. RESULTS: Postoperative course was satisfactory in all patients. At 1 year there was no evidence of stricture or fistula formation and no patient had required reoperation. CONCLUSION: The technique is easy and effective and can be used in open and laparoscopic surgery.

Folliculitis decalvans: a multicentre review of 82 patients.

BACKGROUND: Folliculitis decalvans (FD) is a rare neutrophilic scarring alopecia that represents a therapeutic challenge for dermatologists. OBJECTIVE: To describe the epidemiology, comorbidities, clinical presentation, diagnostic findings and therapeutic options in a large series of patients with FD. METHODS: This retrospective multicentre review includes patients diagnosed with FD based on clinical and histopathologic findings. The clinical severity was determined by the maximum diameter of the largest alopecic patch (slight: <2 cm, moderate: 2-4.99 cm, severe: 5 cm or more). Response to therapy was assessed as improvement, worsening or stabilization depending on the clinical symptoms (pruritus and trichodynia), inflammatory signs (erythema, pustules and crusts) and the extension of the alopecic patch. RESULTS: Overall, 82 patients (52 males and 30 females) with a mean age of 35 years were included. No significant comorbidities were present. A family history was present in three males. Severe FD was observed in 17 patients (21%). The independent factors associated with severe FD after multivariate analysis were: onset of FD before 25 years of age and presence of pustules. Oral antibiotics (tetracyclines and the combination of clindamycin and rifampicin) improved 90% and 100% of the patients, with a mean duration of response of 4.6 and 7.2 months respectively. CONCLUSIONS: The onset of FD before 25 years of age and the presence of pustules within the alopecic patch were associated with severe FD. Tetracyclines and the combination of clindamycin and rifampicin were the most useful treatments.

Insertion of self-expanding metal stent for treatment of malignant obstruction in a pregnant woman.

Colorectal cancer (CRC) is the second most frequent cancer both in incidence and mortality in women, especially in those over 60 years of age. Diagnosis in women at gestational age is rare, so its incidence during pregnancy is low. However, an increase in its diagnosis is expected during the next years because of the raise in the average age of pregnancy.In most cases, the diagnosis is delayed because symptoms related to CRC can be attributed to pregnancy itself. Up to 30 % of CRC cases may present as an intestinal obstruction. In this situation, the main objective is to solve the clinical emergency in the safest way for mother and fetus, together with performing an accurate diagnostic approach to offer the best possible therapeutic management knowing the limitations and difficulties related to pregnancy. The self-expanding metallic stent (SEMS) can be particularly useful in colon obstruction in a pregnant patient with CRC because it allows solving the acute condition providing time to perform a more accurate staging study and to prepare the patient for surgery, thus reducing both post-surgical morbidity and mortality.We report on the case of a patient who early in the second trimester of pregnancy presented with an acute colonic obstruction due to CRC which was successfully managed with the placement of a self-expanding metal stent.

Human intestinal microbiome: Role in health and disease.

The study of the microbiota and the microbiome, and specifically the intestinal one, has determined great interest due to the possible association of their alterations with numerous diseases. These include entities as diverse as Crohn's disease, autism, diabetes, cancer or situations as prevalent today as obesity. In view of this situation, different recommendations have been performed regarding the use of probiotics, prebiotics, and postbiotics as modulators of the microbiota and the microbiome, seeking both preventive and therapeutic effects, and faecal material transfer (FMT) is proposed as an alternative. The latter has emerged as the only proven beneficial intervention on the intestinal microbiome, specifically in the treatment of recurrent colitis associated with Clostridioides difficile (R-CDI). In the rest of the entities, the lowering of laboratory costs has favored the study of the microbiome, which is resolved by delivering reports with catalogs of microorganisms, metabolites or supposed biomarkers without consensus on their composition associated with healthy or diseased microbiota and the disease. There is still insufficient evidence in any disease for interventions on the microbiome beyond FMT and R-CDI. Multi- and multi-disciplinary work with extensive research and the application of artificial intelligence in this field may shed light on the questions raised currently. Ethical issues must also be resolved in light of possible interventions within the umbrella of personalized medicine.

Long-term results with biosynthetic absorbable P4HB mesh in ventral abdominal wall repair: a multicentre analysis.

BACKGROUND: The aim of this multicentre study was to analyse the outcomes of biosynthetic absorbable poly-4-hydroxybutyrate (P4HB) prosthesis implantation in patients undergoing ventral hernia repair (VHR) in the context of different degrees of contamination. METHODS: From May 2016 to December 2021, a multicentre retrospective analysis of patients who underwent elective or urgent hernia repair with P4HB prosthesis was performed in seven hospitals in Spain and Portugal. Patients with a postoperative follow-up of less than 20 months and those within the theoretical period of prosthesis resorption were excluded from the study. Regarding the degree of contamination, patients were assessed according to the modified Ventral Hernia Working Group (VHWG) classification. Epidemiological data, hernia characteristics, surgical and postoperative variables (Clavien-Dindo classification) of these patients were analyzed. Risk factors related to long-term recurrence were studied by a multivariate analysis. RESULTS: In 236 cases of P4HB prosthesis implantation, repair in cases of Grade 3 was the most frequent (49.1%), followed by Grade 2 in 42.3% of cases and Grade 1 in 8.4%. The most frequent complications were Grade 1, with the majority occurring during the first year. The overall rate of surgical site occurrences (SSO) was 30%. The hernia recurrence rate was 14.4% (n = 34), with a mean postoperative follow-up time of 41 months (22-61). The multivariate analysis showed that the onlay location of the mesh (OR 1.07; CI 1.42-2.70, p = 0.004) was a significant independent risk factor for recurrence. CONCLUSIONS: The use of a P4HB bioresorbable mesh for the VHR with different degrees of contamination leads to favourable results overall, with an acceptable rate of hernia recurrence. The onlay location of the P4HB prosthesis is the main factor in recurrence in both elective and emergency settings.

Mathematical birth of Early Afterdepolarizations in a cardiomyocyte model.

Early Afterdepolarizations (EADs) are abnormal behaviors that can lead to cardiac failure and even cardiac death. In this paper we investigate the occurrence and development of these phenomena in a reduced Luo-Rudy cardiac model. Through a comprehensive dynamical analysis, we map out the distinct patterns observed in the parametric plane, differentiating between normal beats without EADs and pathological beats with EADs. By examining the bifurcation structure of the model, we elucidate the dynamical elements associated with these patterns and their transitions. Using a fast-slow analysis, we explore the emergence and evolution of EADs in the model. Notably, our approach combines the two commonly used fast-slow approaches (1-slow-2-fast and 2-slow-1-fast), and we show how both approaches together provide a more complete understanding of this phenomenon.

Near-real time flash drought monitoring system and dataset for Spain.

Flash droughts are characterized by rapid development and intensification, which makes early warning and monitoring difficult. Flash drought monitor (FDM) is a near-real time monitoring system for Spain (https://flash-drought.csic.es) based on the Standardized Precipitation Evapotranspiration Index (SPEI). Flash drought identification was based on rapid and anomalous declines in SPEI at a short time scale (1-month). Thus, FDM enables operational tracking of flash drought conditions in Spain at high spatial resolution (1.1 × 1.1 km) and high temporal frequency (weekly). Likewise, to put flash drought monitoring into a temporal context, the FDM also provides weekly flash drought conditions recorded in Spain from 1961 to the present. The FDM is a useful tool for preparedness and mitigation of flash droughts in Spain. Furthermore, the data provided by the FDM could be useful to develop future studies in relation to the flash drought in Spain.

Complications related to the prehabilitation with preoperative pneumoperitoneum in loss of domain hernias: our experience in 180 consecutive cases.

OBJECTIVE: Progressive pneumoperitoneum (PPP) is useful tool in the preparation of patients with loss of domain hernias (LODH). The purpose of this observational retrospective study was to report our experience in the management of complications associated with the PPP procedure after treating 180 patients with LODH and to report preventive measures to avoid them. METHODS: Of the 971 patients with a ventral incisional hernia operated on between June 2012 and July 2022, 180 consecutive patients with LODH were retrospectively analysed. Diameters of abdominal cavity, and volumes of incisional hernia and abdominal cavity were calculated from CT scan, based on the modified index of Tanaka. Complications related to the PPP procedure (catheter placement and following insufflations of air) were recorded by Clavien-Dindo classification. RESULTS: Complications associated to PPP were 26.6%. No complications occurred during the administration of botulinum toxin (BT). Eighteen patients (10% of 180 patients) developed subcutaneous emphysema during the last days of the insufflations; there were 2 accidental perforations of the small bowel and four punctures with liver and splenic hematomas, detected during catheter placement; a laparotomy, however, was not needed because it was solved with conservative treatment. We diagnosed it as a peritoneum-cutaneous fistula due to the cutaneous atrophy secondary to chronic eventration. CONCLUSION: PPP is a safe technique well tolerated by patients, although at the cost of some specific complications. Hernia surgeons must understand these complications to prevent them and to inform the LODH patient about their existence.

[EPICAP: educational intervention using instructional clips in patients with epilepsy. A randomised clinical trial]. / EPICAP: intervención educativa mediante cápsulas audiovisuales en pacientes con epilepsia. Ensayo clínico aleatorizado.

AIMS: In patients with epilepsy health education has a positive influence on self-management of the disease, improves prognosis and enhances patient well-being. The aim of this study was to evaluate an educational intervention using instructional clips in patients with epilepsy in a video-electroencephalographic monitoring unit. SUBJECTS AND METHODS: We conducted a randomised clinical trial with two groups (intervention and control). Adult patients with epilepsy admitted to the video-electroencephalographic monitoring unit were recruited. Nine videos about the diagnosis and treatment of epilepsy, together with recommendations on lifestyle, were produced and administered to the intervention group while admitted. Patients' knowledge of their disease was assessed by means of a questionnaire designed specifically for this study. A pre-assessment was conducted at the beginning of the study, at hospital discharge and at three months, and the knowledge of epilepsy in the two groups was compared at each time considered in the study. RESULTS: Sixty-six patients were included, with a mean age of 39 ± 14.7 years (range: 17-76) and a median of 8 years since disease onset (range: 1-60 years). Fifty-three per cent of the patients were women. Focal epilepsy was the most frequent type (95.5%). The mean score on the pre-intervention test was 57.2 ± 15.3. Patients who received the educational intervention showed better post-test scores at discharge from hospital (81.8 ± 11.2 versus 62.8 ± 13.7; p = 0.001) and at three months (76 ± 9.6 versus 63.2 ± 12.8; p = 0.001). CONCLUSIONS: The EPICAP educational intervention using instructional clips significantly improves patients' knowledge of epilepsy-related diagnostic, therapeutic and lifestyle issues.

TITLE: EPICAP: intervención educativa mediante cápsulas audiovisuales en pacientes con epilepsia. Ensayo clínico aleatorizado.Objetivos. La educación sanitaria en pacientes con epilepsia influye positivamente en el autocontrol de la enfermedad, mejora su pronóstico y favorece el bienestar del paciente. El objetivo de este estudio fue evaluar una intervención educativa mediante cápsulas audiovisuales en pacientes con epilepsia en una unidad de monitorización videoelectroencefalográfica. Sujetos y métodos. Es un ensayo clínico aleatorizado con dos grupos (intervención y control). Se reclutó a pacientes adultos con epilepsia que ingresaron en la unidad de monitorización videoelectroencefalográfica. Se crearon nueve vídeos sobre el diagnóstico y el tratamiento de la epilepsia, y recomendaciones de estilo de vida, que se administraron al grupo de intervención durante el ingreso. Se evaluó el conocimiento del paciente sobre su enfermedad con un cuestionario diseñado específicamente para este estudio. Se realizó una evaluación previa en el inicio del estudio, en el alta hospitalaria y a los tres meses, y se comparó el conocimiento sobre la epilepsia en ambos grupos en cada momento del estudio. Resultados. Se incluyó a 66 pacientes, con edad media de 39 ± 14,7 años (rango: 17-76) y una mediana de 8 años de evolución de la enfermedad (rango: 1-60 años). Un 53% eran mujeres. El tipo de epilepsia más frecuente fue el focal (95,5%). La puntuación media en el test preintervención fue de 57,2 ± 15,3. Los pacientes que recibieron la intervención educativa mostraron mejores puntuaciones en el postest en el alta hospitalaria (81,8 ± 11,2 frente a 62,8 ± 13,7; p = 0,001) y a los tres meses (76 ± 9,6 frente a 63,2 ± 12,8; p = 0,001). Conclusiones. La intervención educativa EPICAP mediante píldoras audiovisuales mejora de forma significativa el conocimiento de los pacientes sobre aspectos diagnósticos, terapéuticos y estilo de vida relacionados con la epilepsia.

Drought conditions, aridity and forest structure control the responses of Iberian holm oak woodlands to extreme droughts: A large-scale remote-sensing exploration in eastern Spain.

Understanding how Mediterranean forests respond to the increasing frequency of extreme droughts and forest densification is crucial for effective land management in the present context of climate change and land abandonment. We study the responses of Iberian holm oak (Quercus ilex L.) woodlands to recent extreme droughts during 2000-2019 along broad gradients of climate aridity and forest structure. To this purpose, we apply large-scale remote-sensing using MODIS EVI as a primary production proxy in 5274 Q. ilex sites distributed within a 100,000 km2 region in eastern Spain. These woodlands were extensively affected by two extreme drought events in 2005 and 2012. Resistance, assessed as the capacity of the ecosystems to maintain primary production during drought, was significantly lower for semi-arid than for sub-humid and dry-transition conditions. Holm oak woodlands located in semi-arid areas of the region showed also poorer resilience to drought, characterized by low capacity to fully recover to their pre-drought production levels. Further, drought intensity and both pre- and post-drought hydric conditions controlled the variations of resistance, recovery and resilience between the two analyzed extreme drought events. Drought effects were particularly negative for dense Q. ilex stands under semi-arid climate conditions, where strong competition for scarce water resources reduced drought resistance. The observed drought vulnerability of semi-arid holm oak woodlands may affect the long-term stability of these dry forests. Adaptive management strategies, such as selective forest thinning, may be useful for improving drought responses in these more vulnerable semi-arid woodlands. Conversely, natural rewilding may more appropriately guide management actions for more humid areas, where densely developed Q. ilex woodlands show in general a high ability to maintain ecosystem primary production during drought.

Nuclear PARP-1 protein overexpression is associated with poor overall survival in early breast cancer.

BACKGROUND: Poly(ADP-ribose)polymerase-1 (PARP-1) is a highly promising novel target in breast cancer. However, the expression of PARP-1 protein in breast cancer and its associations with outcome are yet poorly characterized. PATIENTS AND METHODS: Quantitative expression of PARP-1 protein was assayed by a specific immunohistochemical signal intensity scanning assay in a range of normal to malignant breast lesions, including a series of patients (N = 330) with operable breast cancer to correlate with clinicopathological factors and long-term outcome. RESULTS: PARP-1 was overexpressed in about a third of ductal carcinoma in situ and infiltrating breast carcinomas. PARP-1 protein overexpression was associated to higher tumor grade (P = 0.01), estrogen-negative tumors (P < 0.001) and triple-negative phenotype (P < 0.001). The hazard ratio (HR) for death in patients with PARP-1 overexpressing tumors was 7.24 (95% CI; 3.56-14.75). In a multivariate analysis, PARP-1 overexpression was an independent prognostic factor for both disease-free (HR 10.05; 95% CI 5.42-10.66) and overall survival (HR 1.82; 95% CI 1.32-2.52). CONCLUSIONS: Nuclear PARP-1 is overexpressed during the malignant transformation of the breast, particularly in triple-negative tumors, and independently predicts poor prognosis in operable invasive breast cancer.