Combining Native Mass Spectrometry and Proteomics to Differentiate and Map the Metalloform Landscape in Metallothioneins.

Within the intricate landscape of the proteome, approximately 30% of all proteins bind metal ions. This repertoire is even larger when considering all the different forms of a protein, known as proteoforms. Here, we propose the term "metalloforms" to refer to different structural or functional variations of a protein resulting from the binding of various hetero- or homogeneous metal ions. Using human Cu(I)/Zn(II)-metallothionein-3 as a representative model, we developed a chemical proteomics strategy to simultaneously differentiate and map Zn(II) and Cu(I) metal binding sites. In the first labeling step, N-ethylmaleimide reacts with Cysteine (Cys), resulting in the dissociation of all Zn(II) ions while Cu(I) remains bound to the protein. In the second labeling step, iodoacetamide is utilized to label Cu(I)-bound Cys residues. Native mass spectrometry (MS) was used to determine the metal/labeling protein stoichiometries, while bottom-up/top-down MS was used to map the Cys-labeled residues. Next, we used a developed methodology to interrogate an isolated rabbit liver metallothionein fraction containing three metallothionein-2 isoforms and multiple Cd(II)/Zn(II) metalloforms. The approach detailed in this study thus holds the potential to decode the metalloproteoform diversity within other proteins.

Variable Energy and Ultrasound-based Liposculpture of the Arms: Multicenter and Multidevice Study.

Incorporation of new technologies to assist the liposuction procedure is becoming increasingly common. These technologies allow for a softer technique, balanced shaping, elimination of excess adipose tissue, and skin tightening. Some of these technologies include ultrasound (US; US-assisted liposculpture, VASER-assisted liposuction), power suction (power-assisted liposuction), radiofrequency (RF; RF-assisted lipolysis), and laser (laser-assisted liposuction). In addition, some of these devices have been shown to reduce the incidence of hematomas/inflammation and shorten recovery time. We report our experience in high-definition liposculpture of the arms in addition to new technologies to improve skin retraction, comparing their results in terms of complications, satisfaction score, and aesthetic outcomes. We included patients with mild-to-moderate arm dermatochalasis (Duncan classification) fat deposits in the upper extremities who were considered candidates for third-generation US-assisted liposculpture, power-assisted liposuction, RF-assisted lipolysis/skin tightening, and laser-assisted liposuction. A total of 683 consecutive patients met the inclusion criteria for the study. Most of them were women (n = 605, 88%). Fat grafting was performed in 80 patients (11.7%). A significant portion of the patients were secondary cases (n = 223, 33%). Age ranged from 18 to 70 years (median = 38 years). BMI ranged from 17.8 to 34.8 kg/m2 (mean = 24.3 kg/m2). RF-assisted and laser-assisted high-definition liposculpture of the arms are both effective and reproducible techniques for patients who seek an athletic and slim arm contour. A low rate of complications and high satisfaction index support our findings.

Synchronic distribution of the dinoflagellate Protoceratium reticulatum and yessotoxins in a high stratified fjord system: Tidal or light modulation?

Protoceratium reticulatum is the main yessotoxin-producer along the Chilean coast. Thus far, the yessotoxin levels recorded in this region have not posed a serious threat to human health. However, a bloom of P. reticulatum during the austral summer of 2022 caused the first ban of shellfish collection, due to the high toxin levels. A bloom of P. reticulatum during the austral summer of 2020 allowed an evaluation of the fine-scale distribution of the dinoflagellate during a tidal cycle. High-resolution measurements of biophysical properties were carried out in mid-summer (February 18-19) at a fixed sampling station in Puyuhuapi Fjord, Chilean Patagonia, as part of an intensive 24-h biophysical experiment to monitor the circadian distributions of P. reticulatum vegetative cells and yessotoxins. High P. reticulatum cell densities (>20 × 103 cells L-1) were found in association with a warmer (14.5-15 °C) and estuarine (23.5-24.5 g kg-1) sub-surface water layer (6-8 m). P. reticulatum cell numbers and yessotoxins followed a synchronic distribution pattern consistent with the excursions of the pycnocline. Nevertheless, the surface aggregation of the cells was modulated by the light cycle, suggesting daily vertical migration. The yessotoxin content per P. reticulatum cell ranged from 9.4 to 52.2 pg. This study demonstrates both the value of fine-scale resolution measurements of biophysical properties in a highly stratified system and the potential ecosystem impact of P. reticulatum strains producing high levels of yessotoxins.

Advanced interpenetrating polymer networks for innovative gastroretentive formulations targeting Helicobacter pylori gastric colonization.

The escalating challenges of Helicobacter pylori-induced gastric complications, driven by rising antibiotic resistance and persistent cancer risks, underscore the demand for innovative therapeutic strategies. This study addresses this urgency through the development of tailored semi-interpenetrating polymer networks (semi-IPN) serving as gastroretentive matrices for amoxicillin (AMOX). They are biodegradable, absorb significant volume of simulated gastric fluid (swelling index > 360 %) and exhibit superporous microstructures, remarkable mucoadhesion, and buoyancy. The investigation includes assessment at pH 1.2 for comparative analysis with prior studies and, notably, at pH 5.0, reflecting the acidic environment in H. pylori-infected stomachs. The semi-IPN demonstrated gel-like structures, maintaining integrity throughout the 24-hour controlled release study, and disintegrating upon completing their intended function. Evaluated in gastroretentive drug delivery system performance, AMOX release at pH 1.2 and pH 5.0 over 24 h (10 %-100 %) employed experimental design methodology, elucidating dominant release mechanisms. Their mucoadhesive, buoyant, three-dimensional scaffold stability, and gastric biodegradability make them ideal for accommodating substantial AMOX quantities. Furthermore, exploring the inclusion of the potassium-competitive acid blocker (P-CAB) vonoprazan (VONO) in AMOX-loaded formulations shows promise for precise and effective drug delivery. This innovative approach has the potential to combat H. pylori infections, thereby preventing the gastric cancer induced by this pathogen.

RANKL, but Not R-Spondins, Is Involved in Vascular Smooth Muscle Cell Calcification through LGR4 Interaction.

Vascular calcification has a global health impact that is closely linked to bone loss. The Receptor Activator of Nuclear Factor Kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, fundamental for bone metabolism, also plays an important role in vascular calcification. The Leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), a novel receptor for RANKL, regulates bone remodeling, and it appears to be involved in vascular calcification. Besides RANKL, LGR4 interacts with R-spondins (RSPOs), which are known for their roles in bone but are less understood in vascular calcification. Studies were conducted in rats with chronic renal failure fed normal or high phosphorus diets for 18 weeks, with and without control of circulating parathormone (PTH) levels, resulting in different degrees of aortic calcification. Additionally, vascular smooth muscle cells (VSMCs) were cultured under non-calcifying (1 mM phosphate) and calcifying (3 mM phosphate) media with different concentrations of PTH. To explore the role of RANKL in VSMC calcification, increasing concentrations of soluble RANKL were added to non-calcifying and calcifying media. The effects mediated by RANKL binding to its receptor LGR4 were investigated by silencing the LGR4 receptor in VSMCs. Furthermore, the gene expression of the RANK/RANKL/OPG system and the ligands of LGR4 was assessed in human epigastric arteries obtained from kidney transplant recipients with calcification scores (Kauppila Index). Increased aortic calcium in rats coincided with elevated systolic blood pressure, upregulated Lgr4 and Rankl gene expression, downregulated Opg gene expression, and higher serum RANKL/OPG ratio without changes in Rspos gene expression. Elevated phosphate in vitro increased calcium content and expression of Rankl and Lgr4 while reducing Opg. Elevated PTH in the presence of high phosphate exacerbated the increase in calcium content. No changes in Rspos were observed under the conditions employed. The addition of soluble RANKL to VSMCs induced genotypic differentiation and calcification, partly prevented by LGR4 silencing. In the epigastric arteries of individuals presenting vascular calcification, the gene expression of RANKL was higher. While RSPOs show minimal impact on VSMC calcification, RANKL, interacting with LGR4, drives osteogenic differentiation in VSMCs, unveiling a novel mechanism beyond RANKL-RANK binding.

Challenges in Psoriasis Research: A Systematic Review of Preclinical Models.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease with variable clinical presentation, multifactorial etiology and an immunogenetic basis. Several studies demonstrate that it results from a dysregulated interaction between skin keratinocytes, immune cells, and the environment that leads to a persistent inflammatory process modulated by cytokines and T cells. The development of new treatment options requires increased understanding of pathogenesis. However, the successful implementation of effective drugs requires well-characterized and highly available preclinical models that allow researchers to quickly and reproducibly determine their safety and efficacy. METHODS: A systematic search on PubMed and Scopus databases was performed and assessed to find appropriate articles about psoriasis models applying the key words previously defined. The PRISMA guidelines were employed. RESULTS: A total of 45 original articles were selected that met the selection criteria. Among these, there are articles on in vivo, in vitro, and ex vivo models, with the in vitro model being the majority due to its ease of use. Within animal models, the most widely used in recent years are chemically induced models using a compound known as imiquimod. However, the rest of the animal models used throughout the disease's research were also discussed. On the other hand, in vitro models were divided into two and three dimensions. The latter were the most used due to their similarity to human skin. Lastly, the ex vivo models were discussed, although they were the least used due to their difficulty in obtaining them. CONCLUSIONS: Therefore, this review summarizes the current preclinical models (in vivo, in vitro, and ex vivo), discussing how to develop them, their advantages, limitations, and applications. There are many challenges to improve the development of the different models. However, research in these in vitro model studies could reduce the use of animals. This is favored with the use of future technologies such as 3D bioprinting or organ-on-a-chip technologies.

Development and Characterization of a Microemulsion Containing a Cannabidiol Oil and a Hydrophilic Extract from Sambucus ebulus for Topical Administration.

Cannabidiol (CBD) is a safe and non-psychotropic phytocannabinoid with a wide range of potential therapeutic anti-inflamatory and antioxidant activities. Due to its lipophilicity, it is normally available dissolved in oily phases. The main aim of this work was to develop and characterize a new formulation of a microemulsion with potential anti-inflammatory and antioxidant activity for the topical treatment of inflammatory skin disorders. The microemulsion system was composed of a 20% CBD oil, which served as the hydrophobic phase; Labrasol/Plurol Oleique (1:1), which served as surfactant and cosurfactant (S/CoS), respectively; and an aqueous vegetal extract obtained from Sambucus ebulus L. (S. ebulus) ripe fruits, which has potential anti-oxidant and anti-inflammatory activity and which served as the aqueous phase. A pseudo-ternary phase diagram was generated, leading to the selection of an optimal proportion of 62% (S/CoS), 27% CBD oil and 11% water and, after its reproducibility was tested, the aqueous phases were replaced by the vegetal hydrophilic extract. The defined systems were characterized in terms of conductivity, droplet size (by laser scattering), compatibility of components (by differential scanning calorimetry) and rheological properties (using a rotational rheometer). The designed microemulsion showed good stability and slight pseudo-plastic behavior. The release properties of CBD from the oil phase and caffeic acid from the aqueous phase of the microemulsion were studied via in vitro diffusion experiments using flow-through diffusion cells and were compared to those of a CBD oil and a microemulsion containing only CBD as an active substance. It was found that the inclusion of the original oil in microemulsions did not result in a significant modification of the release of CBD, suggesting the possibility of including hydrophilic active compounds in the formulation and establishing an interesting strategy for the development of future formulations.

Epidemiology, use, and practice of the intraosseous route in an out-of-hospital emergency department: a retrospective cross-sectional study.

Introduction: The Spanish Emergency Medical Services, according to the model we know today, were formed during the 80s and 90s of the 20th century. The Health Emergency Service (EMS), 061 La Rioja, began to assist the population of La Rioja in November 1999. An essential part of the mission of the SES is the provision of care and the transfer of critical patients using advanced life support unit (ALSU) techniques. In daily practice, out-of-hospital emergency services are faced with situations in which they must deal with the care of serious or critically ill patients, in which the possibility of being able to channel peripheral vascular access as part of ALSU quickly may be difficult or impossible. In these cases, cannulation of intraosseous (IO) vascular access may be the key to early and adequate care. Aim: This study aimed to determine the incidence and epidemiology use of IO vascular access in SES 061 La Rioja during the year 2022. Matherial and methods: We performed observational retrospective cross-sectional studies conducted in 2022. It included a population of 4.364 possible patients as a total of interventions in the community of La Rioja in that year. Results: A total of 0.66% of patients showed a clinical situation that required the establishment of IO vascular access to enable out-of-hospital stabilization; this objective was achieved in 41.3%. A total of 26.1% of patients who presented with cardiorespiratory arrest (CA) were stabilized, while 100% presented with shock and severe trauma. Discussion: IO vascular access provides a suitable route for out-of-hospital stabilization of critically ill patients when peripheral vascular access is difficult or impossible.

Antithrombotic Use Patterns in COVID-19 Patients from Spain: A Real-World Data Study.

Antithrombotics have been widely used to treat and prevent COVID-19-related thrombosis; however, studies on their use at population levels are limited. We aimed to describe antithrombotic use patterns during the pandemic in Spanish primary care and hospital-admitted patients with COVID-19. Methods: A real-world data study was performed. Data were obtained from BIFAP's electronic health records. We investigated the antithrombotic prescriptions made within ±14 days after diagnosis between March 2020 and February 2022, divided their use into prior and new/naive groups, and reported their post-discharge use. Results: We included 882,540 individuals (53.4% women), of whom 78,499 were hospitalized. The median age was 44.7 (IQR 39-59). Antithrombotics were prescribed in 37,183 (4.6%) primary care subjects and 42,041 (53.6%) hospital-admitted patients, of whom 7505 (20.2%) and 20,300 (48.3%), respectively, were naive users. Prior users were older and had more comorbidities than new users. Enoxaparin was the most prescribed antithrombotic in hospitals, with higher prescription rates in new than prior users (2348.2, IQR 2390-3123.1 vs. 1378, IQR 1162-1751.6 prescriptions per 10,000 cases, p = 0.002). In primary care, acetylsalicylic acid was the most used antithrombotic, with higher use rates in prior than in naïve users. Post-discharge use occurred in 6686 (15.9%) subjects (median use = 10 days, IQR 9-30). Conclusions: Our study identified a consensus on prescribing antithrombotics in COVID-19 patients, but with low use rates in hospitals.

Approximation to the economic cost of healthcare for hypertensive patients diagnosed with COVID-19.

Introduction: Many researchers have focused their studies on hypertension due to its over-representation among COVID-19 patients. Both retrospective and observational studies conducted close to the Wuhan area have reported that hypertension is the most common comorbidity observed in patients affected by COVID-19. Objective: Our objective is that patients with arterial hypertension have a worse prognosis in terms of evolution leading to higher costs. Methods: A retrospective cross-sectional study was conducted. A total of 3,581 patients from La Paz University Hospital (LPUH) during the period between 15 July 2020 and 31 July 2020 were included in this study. Results: It should be noted that 40.71% of the patients were hypertensive. As expected, hypertension was associated with men, among whom we observed a higher prevalence and a higher age (median age of 77 years (IQI: 65-85) versus 52 years (IQI: 37-64), p-value < 0.001). Hypertensive patients had a higher prevalence of dyspnea (52.14% vs. 47.15%, p-value = 0.004) and altered awareness (14.89% vs. 4.30%, p-value <0.001). The non-parametric Kaplan-Meier curve estimates the survival of patients in the two study groups. We can see how patients with hypertension have a higher associated mortality, with the difference being statistically significant, p-value (log-rank) = 0.004. Only for the appearance of complications during hospitalization, the group of hypertensive patients reached the figure of €1,355,901.71 compared to the total of 421,403.48 € for normotensive patients. Conclusion: Our study shows the worse clinical evolution of patients with COVID-19 in terms of associated morbidity and mortality. It also shows that the cost of managing patients with hypertension is greater than that of managing normotensive patients.

Seguimiento a muy largo plazo tras implante de stent en la coartación de aorta / Very long-term follow-up after aortic stenting for coarctation of the aorta

Introducción y objetivos: El implante de stent es el tratamiento de elección en niños mayores y adultos con coartación aórtica (CoA). El objetivo fue determinar la incidencia de eventos tardíos después del tratamiento con stent. Métodos: Se analizó una cohorte de pacientes con CoA tratados en el centro entre 1993 y 2018 a los que se siguió periódicamente, incluyendo evaluación mediante tomografía computarizada (TC) y fluoroscopia. Resultados: Se incluyó a 167 pacientes con TC y fluoroscopia: 83 (49,7%) ≤ 12 años y 46 (28%) mujeres. El tiempo medio de seguimiento clínico fue de 17±8 años (rango 4-30) y de 11±7 años hasta la TC/fluoroscopia. Se detectó aneurisma en un 13% y se asoció al stent PALMAZ (OR=3,09; IC95%, 1,11-9,49; p=0,036) y a la longitud del stent (OR=0,94; IC95%, 0,89-0,99; p=0,039). La fractura del stent fue frecuente (34%) pero no asociada a la presencia de aneurisma. Se asoció con edad joven (OR=3,57; IC95%, 1,54-8,33; p=0,003), sexo masculino (OR=4,00; IC95%, 1,51-12,50; p=0,008) e inversamente con el stent PALMAZ (OR=0,29; IC95%, 0,12-0,67; p=0,005). La reintervención fue menor en adultos (10%), principalmente por aneurismas. Los pacientes que recibieron tratamiento cuando tenían 12 años o menos presentaron tasas de reintervención más altas (43%) debido al crecimiento somático. Conclusiones: Se observó una incidencia notable de eventos tardíos a largo plazo en pacientes con CoA tratados mediante stent. La reintervención fue más frecuente en pacientes tratados a edades más jóvenes. Parece aconsejable una vigilancia periódica mediante pruebas de imagen. (AU)

Introduction and objectives: Stent implantation is the preferred treatment in older children and adults with aortic coarctation (CoA). We aimed to determine the incidence of very late events after CoA stenting. Methods: We analyzed a cohort of CoA patients who underwent stent implantation at our center between 1993 and 2018. Patients were periodically followed up in outpatient clinics, including computed tomography (CT) and fluoroscopy assessment. Results: A total of 167 patients with CT and fluoroscopy data were included: 83 (49.7%) were aged ≤ 12 years and 46 (28%) were female. The mean clinical follow-up time was 17±8 (range 4-30) years and the mean time to CT/fluoroscopy was 11±7 years. Aortic aneurysm was present in 13% and was associated with the PALMAZ stent (OR, 3.09; 95%CI, 1.11-9.49; P=.036) and the stented length (OR, 0.94; 95%CI, 0.89-0.99; P=.039). Stent fracture was frequent (34%), but was not related to the presence of aneurysm. Stent fracture was associated with young age (OR, 3.57; 95%CI, 1.54-8.33; P=.003), male sex (OR, 4.00; 95%CI, 1.51-12.5, P=.008) and inversely with the PALMAZ stent (OR, 0.29; 95%CI, 0.12-0.67, P=.005). Reintervention was lower in adults (10%), mainly related to aneurysms. Those treated when aged ≤ 12 years had higher reintervention rates (43%) due to recoarctation somatic growth. Conclusions: This long-term follow-up study of CoA patients treated with stenting revealed a significant incidence of late events. Reintervention rates were higher in patients treated at younger ages. Periodic imaging surveillance appears to be advisable. (AU)

Anxiety, depression, and alcohol use disorder in dermatologists: relationship with burnout and associated risk factors.

Burnout syndrome is a mental health condition related to chronic occupational stress; its prevalence, as well as its relationship with other mental health disorders in physicians, has become a topic of growing interest. However, no studies with large sample sizes evaluate this association in dermatologists. With this background, a cross-sectional study was designed, which included 420 Spanish dermatologists; the mean age was 44.5 years (12.39), and 62% (260/420) were women. Eleven percent (45/420) of the participants presented a moderate risk of burnout, more than half of the sample had at least one of the burnout symptoms, 47% (198/420) had some degree of anxiety, and 20.3% (85/420) presented some degree of depression. Less than 1% (4/420) demonstrated a high risk of alcohol use disorder. Being female was associated with a higher risk of depression and anxiety. Meanwhile, men and residents showed an increasedrisk of alcohol use disorder. Burnout and its domains showed a significative association with depression and anxiety, while no relationship with alcohol abuse was observed.

Novel Biomarkers of Bone Metabolism.

Bone represents a metabolically active tissue subject to continuous remodeling orchestrated by the dynamic interplay between osteoblasts and osteoclasts. These cellular processes are modulated by a complex interplay of biochemical and mechanical factors, which are instrumental in assessing bone remodeling. This comprehensive evaluation aids in detecting disorders arising from imbalances between bone formation and reabsorption. Osteoporosis, characterized by a reduction in bone mass and strength leading to heightened bone fragility and susceptibility to fractures, is one of the more prevalent chronic diseases. Some epidemiological studies, especially in patients with chronic kidney disease (CKD), have identified an association between osteoporosis and vascular calcification. Notably, low bone mineral density has been linked to an increased incidence of aortic calcification, with shared molecules, mechanisms, and pathways between the two processes. Certain molecules emerging from these shared pathways can serve as biomarkers for bone and mineral metabolism. Detecting and evaluating these alterations early is crucial, requiring the identification of biomarkers that are reliable for early intervention. While traditional biomarkers for bone remodeling and vascular calcification exist, they suffer from limitations such as low specificity, low sensitivity, and conflicting results across studies. In response, efforts are underway to explore new, more specific biomarkers that can detect alterations at earlier stages. The aim of this review is to comprehensively examine some of the emerging biomarkers in mineral metabolism and their correlation with bone mineral density, fracture risk, and vascular calcification as well as their potential use in clinical practice.

Prolonged cold-preservation of domestic cat ovarian tissue is improved by extracellular solution but impaired by the fragmentation of ovary.

For domestic cats ovaries, recommended cold-storage limit is 24 h in Phosphate Buffered Saline (PBS) or Dulbecco`s PBS (DPBS). Here, we attempted to verify wheatear cat ovaries may benefit from more complex solutions during prolonged cold-storage (>24 h). First, the preservation capabilities of extracellular (SP+), intracellular (UW) solutions and DPBS supplemented with glutathione (DPBS+GSH) were compared using ovary fragments from the same ovary (n=10). Intact ovary stored in DPBS served as a control. Ovaries were kept at 4 °C for 48 h, and 72 h. In the second experiment, first ovary was stored in DPBS, second in SP+ or UW solution for 48 h (n = 12). Ovaries pairs stored in DPBS for 24 h served as a control (n=8). Tissue samples were evaluated directly after cold-storage and after following 24 h in vitro culture. Ovarian follicle morphology, apoptosis rates (cleaved caspase-3, TUNEL), and follicular growth activation (Ki-67) were assessed. Ovary fragmentation impaired follicular morphology preservation upon cold-storage comparing to intact ovary. However, ovarian fragments stored in UW for 48 h and in SP+ for 72 h presented better morphology than DPBS+GSH group. Comparison of intact ovaries cold-storage for 48 h showed that SP+ provided superior follicular morphology over DPBS, and it was comparable to the outcome of 24-hour storage. No follicular activation after in vitro culture was observed. Nevertheless, tissue culture increased considerably caspase-3 cleavage and TUNEL detection. The ovary fragmentation prior to cold-storage is not recommended in domestic cats. Replacement of DPBS with SP+ solution for whole ovary and UW solution for ovarian tissue fragments improves follicular structure preservation during 48-hour cold-storage.

An Unprecedented Bloom of Oceanic Dinoflagellates (Karenia spp.) Inside a Fjord within a Highly Dynamic Multifrontal Ecosystem in Chilean Patagonia.

At the end of summer 2020, a moderate (~105 cells L-1) bloom of potential fish-killing Karenia spp. was detected in samples from a 24 h study focused on Dinophysis spp. in the outer reaches of the Pitipalena-Añihue Marine Protected Area. Previous Karenia events with devastating effects on caged salmon and the wild fauna of Chilean Patagonia had been restricted to offshore waters, eventually reaching the southern coasts of Chiloé Island through the channel connecting the Chiloé Inland Sea to the Pacific Ocean. This event occurred at the onset of the COVID-19 lockdown when monitoring activities were slackened. A few salmon mortalities were related to other fish-killing species (e.g., Margalefidinium polykrikoides). As in the major Karenia event in 1999, the austral summer of 2020 was characterised by negative anomalies in rainfall and river outflow and a severe drought in March. Karenia spp. appeared to have been advected in a warm (14-15 °C) surface layer of estuarine saline water (S > 21). A lack of daily vertical migration patterns and cells dispersed through the whole water column suggested a declining population. Satellite images confirmed the decline, but gave evidence of dynamic multifrontal patterns of temperature and chl a distribution. A conceptual circulation model is proposed to explain the hypothetical retention of the Karenia bloom by a coastally generated eddy coupled with the semidiurnal tides at the mouth of Pitipalena Fjord. Thermal fronts generated by (topographically induced) upwelling around the Tic Toc Seamount are proposed as hot spots for the accumulation of swimming dinoflagellates in summer in the southern Chiloé Inland Sea. The results here provide helpful information on the environmental conditions and water column structure favouring Karenia occurrence. Thermohaline properties in the surface layer in summer can be used to develop a risk index (positive if the EFW layer is thin or absent).

Soluble Klotho, a Potential Biomarker of Chronic Kidney Disease-Mineral Bone Disorders Involved in Healthy Ageing: Lights and Shadows.

Shortly after the discovery of Klotho, interest grew in its potential role in chronic kidney disease (CKD). There are three isoforms of the Klotho protein: αKlotho, ßKlotho and γKlotho. This review will focus on αKlotho due to its relevance as a biomarker in CKD. αKlotho is synthesized mainly in the kidneys, but it can be released into the bloodstream and urine as soluble Klotho (sKlotho), which undertakes systemic actions, independently or in combination with FGF23. It is usually accepted that sKlotho levels are reduced early in CKD and that lower levels of sKlotho might be associated with the main chronic kidney disease-mineral bone disorders (CKD-MBDs): cardiovascular and bone disease. However, as results are inconsistent, the applicability of sKlotho as a CKD-MBD biomarker is still a matter of controversy. Much of the inconsistency can be explained due to low sample numbers, the low quality of clinical studies, the lack of standardized assays to assess sKlotho and a lack of consensus on sample processing, especially in urine. In recent decades, because of our longer life expectancies, the prevalence of accelerated-ageing diseases, such as CKD, has increased. Exercise, social interaction and caloric restriction are considered key factors for healthy ageing. While exercise and social interaction seem to be related to higher serum sKlotho levels, it is not clear whether serum sKlotho might be influenced by caloric restriction. This review focuses on the possible role of sKlotho as a biomarker in CKD-MBD, highlighting the difference between solid knowledge and areas requiring further research, including the role of sKlotho in healthy ageing.